The key factor of chemotherapy for brain disorders is to penetrate brain blood barrier(BBB). Receptor mediated en-docytosis is one of the mechanisms for drug carriers to cross the BBB. Angiopep-2(ANG)can specifically bind to low density lipopro-tein receptor-related proteins 1(LRP-1)overexpressed on BBB and glioma cells,thus exhibits a higher LRP-mediated BBB penetra-tion capability. Its targeting efficiency is higher than that of other targeting molecules such as transferrin and(TF)lactoferrin(LF). This paper introduces the structure and function of ANG,and its application in brain targeting delivery systems,in order to provide references for research and development of brain targeting preparations and guidance for therapy of brain diseases.

Objective To establish a rabbit model of lumbar laminectomy and bone grains replantation and provide experimental evidence for the clinical application.Methods Eighteen healthy male New Zealand rabbits were selected and randomly divided into two groups:the control group (n=6) and experimental group (n=12).The rabbits of control group were given general anesthesia, and taking the L5 spinous process as the center to perfom left L5 laminectomy, using a micro lancet forceps to slowly bite the lamina and ligamentum flavum for fenestration and exposed to an approximately 0.8 cm x 0.3 cm sized bone window and then sutured the skin.The rabbits of experimental group were exposed to an approximately 0.8 x 0.3 cm sized bone window as well, and bone fragments were cut into small grains.Then the small bone grains were embedded in medical collagen sponge, to form an arch shape, and replanted them to the site of epidural fenestration.CT scan and histological changes were observed at 4, 8 and 12 weeks after operation.Results At 8 weeks after operation, CT examination showed that in the experimental group, a thin bone plate was formed by the bone grains.At 12 weeks after operation, the bone plate became thicker and was connected with the vertebral bone, and with continuous bone trabeculae.The spinal canal and volume were not obviously changed, and no spinal cord compression was observed. The rabbits of control group showed segment lamina defects, a small scar protruding into the spinal canal, and the vertebral canal was not completely reconstructed. Conclusions The bone grains replantation can effectively promote bone reconstruction in the laminectomized rabbits, and the formed bone plate can prevent epidural scar from intruding into the spinal canal, and can reduce the postlaminectomy adhesion.

Objective To conduct breath test with a relatively large number of subjects for new data regarding breath acetone in diabetes using a high accuracy and high data throughput breath acetone analyzer based on the cavity ringdown spectroscopy (CRDS) technique.Methods The CRDS breath analyzer was validated by standard acetone gas samples with various concentrations and golden standard gas chromatography-mass spectrometry (GC-MS).A total of 917 breath samples from 260 type 2 diabetic (T2D) patients and 30 healthy individuals were collected under each of 4 different conditions: fasting, 2 h post-breakfast, 2 h post-lunch, and 2 h post-dinner, and the samples were tested by the breath analyzer.Results The linear fitting curve of standard acetone samples with various concentration had good linearity (R=1, P＜0.05).The linear fitting of the results of GC-MS and CRDS was 0.98, suggesting that the obtained acetone concentrations using both methods were consistent.For the 260 T2D subjects, the exhaled breath acetone concentrations ranged from 0.0 to 10.6×10-6, while for the 30 healthy subjects, the breath acetone concentration ranged from 0.1 × 10-6 to 2.0× 10-6.The mean breath acetone concentration of the 260 T2D subjects was (1.5±1.l)× 10-6, which was 1.4 times of(1.1±0.5)×10-6 for the 30 healthy subjects.The mean breath acetone concentrations under the 4 conditions for the 260 T2D subjects ((1.6±1.2)×10-6, (1.4±1.0)×10-6~, (1.4±0.9)×10-6, and (1.4±1.2)× 10-6) were higher than that of the 30 healthy subjects ((1.3±0.3)×10-6, (1.0±0.6)×10-6, (1.0±0.6)×10-6, and (1.1±0.4)×10-6), respectively.No correlation was found between the breath acetone concentration and the blood glucose level of the T2D subjects and the healthy individuals.Conclusions The GC-MS validation confirms that the CRDS breath acetone analyzer is a reliable instrument for fast response and on-line breath acetone measurement.An elevated mean breath acetone concentration exists in T2D subjects.The relationship between breath acetone level and physiological parameters needs to be further investigated.

Objective To investigate the effects of the head peripheral nerve block on remifentanil consumption and postoperative pain in patients undergoing craniocerebral surgery. Methods 80 patients under general anesthesia undergoing supratentorial craniocerebral surgery were randomly divided into two groups:the head peripheral nerve block combined intravenous anesthesia group (group S, 40 cases) and the simple intravenous anesthesia group (group C, 40 cases). After anesthesia induction intubation, the patients in group S received the head peripheral nerve block with 0.596% ropivacaine mesylate injection,including supraorbital nerve, supratrochlear nerve , auriculotemporal nerve , great occipital nerve and lesser occipital nerve , as well as regional nerve on the corresponding position of the bilateral head nails. Haemodynamic index of the operations was measured;drug consumption during operation and VAS pain score at 0. 5, 2, 6, 12, 24 and 48 h after surgery were recorded. Results Compared with group C, the values of SBP, DBP, HR had a significant decrease at head-nail insertion and the latter stage in group S(P<0.05). The remifentanil consumption and VAS scores had a significant decrease in group S (P < 0.05). Conclution Head peripheral nerve block before operation could enhance anesthesic analgesia, reduce the remifentanil consumption and postoperative pain in patients undergoing craniocerebral surgery.

Objective To investigate the clinical risk factors of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH).Methods From January 2015 to April 2016,106 consecutive patients with aSAH treated with endovascular embolization at the Department of Neurosurgery,Nanjing General Hospital of Nanjing Military Command were enrolled retrospectively.The patients were divided into either a DCI group (n =34) or a non-DCI group (n =72) according to whether the occurrence of DCI.The general information of patients were collected,including sex,age,Hunt-Hess grade,modified Fisher grade,world federation of neurosurgical societies (WFNS) grade,acute cerebral edema,early (bleeding 1-3 d) hypoalbuminemia,and hypohemoglobinemia.Univariate and multivariate Logistic regression analyses were used to analyze the risk factors for occurrence of DCI.Results The incidence of DCI was 32.1％ (34/106).The Hunt-Hess grade ≥ Ⅲ,modified Fisher grade ≥ Ⅲ,WFNS grade ≥ Ⅳ,acute cerebral edema,the incidences of hypoalbuminemia and hypohemoglobinemia in the DCI group were higher than those in the non-DCI group.There were significant differences between the 2 groups (all P ＜ 0.05).There were no significant differences in the ratios of sex,age ≥ 55 years,hypertension,diabetes and hyponatremia between the 2 groups (all P ＞ 0.05).In univariate analysis,the Hunt-Hess grade ≥ Ⅲ grade,modified Fisher grade ≥ Ⅲ,WFNS grade ≥ Ⅳ on admission,and hypoalbuminemia were used as the independent variables for multivariate analysis,the results showed that WFNS grade ≥ Ⅳ (OR,8.02;95 ％ CI 2.41-26.70),modified Fisher grades ≥ Ⅲ (OR,4.44;95％ CI 1.38-14.32),and hypoalbuminemia at day 1-3 (OR,5.42;95％ CI 1.40-20.76) were the independent risk factors for occurring DCI in patients with aSAH (all P ＜ 0.05),and the Hunt-Hess grade ≥ Ⅲ was not the risk factor for occurring DCI in patients with aSAH (OR,1.86;95％ CI 0.39-8.88,P ＞ 0.05).Conclusion The patients with hypoalbuminemia,WFNS grade≥Ⅳ on adrnission,and modified Fisher grade ≥ Ⅲ may were the independent risk factors DCI after aSAH,and the clinical diagnosis and treatment should attach great importance to.

Objective: To evaluate the application effect of the platform switching implants in maxillary anterior region, to explore the effect of platform switching technology on the surrounding tissues. Methods: 55 patients with 60 single maxillary anterior implants were divided into two groups: platform-switching implants group (Ankylos), 25 patients with 28 implants; butt-joint implants group (Nobel Replace), 30 patients with 32 implants. The patients received follow-up care more than 1 and 2 year after the final setting of the prosthesis, at which time periapical radiographs were taken. The marginal bone level around the implant and Pink Esthetic Score (PES) were measured for comparison. Results : The average marginal bone changes of platform-switching implants after 1 year and 2 year were (-0.41 ± 0.36) mm and (-0.55 ± 0.33) mm respectively; and the ones of butt-joint implants were (-1.77 ± 0.54) mm and (-1.82 ± 0.61) mm. The average PES of platform- switched implants after 1 year and 2 year were 10.43 ± 1.37 and 10.32 ± 1.21 respectively; the ones of butt-joint implants were 9.21 ± 0.97 and 9.16 ± 0.95. There were significantly differences of marginal bone changes and PES between both groups (P < 0.05). Conclusion Platform switching implant in the maxillary aesthetics area is more effective in preserving the surrounding bone tissue and aesthetic effect.

Exhausted CD8 + T cells (CD8 + Tex) are a distinct subpopulation formed from naive CD8 + T cells under conditions of sustained high antigen stimulation. Initially, naive CD8 + T cells can differentiate into functional cytotoxic cells and exert anti-infective and anti-tumor effects upon short-term antigen stimulation. However, sustained high antigen stimulation will make effector CD8 + T cells progressively differentiate into terminally CD8 + Tex cells and irreversibly lose effector function. Unlike memory and effector T cells, CD8 + Tex cells have a unique transcriptional program. Numerous studies are attempting to map a detailed differentiation landscape of CD8 + Tex cell subsets, aiming to maximize the number of effector T cells in the future by targeting individual subsets or individual differentiation stages in CD8 + Tex cells without damaging the effector cells. This article reviewed the progress in CD8 + Tex cells from the aspects of transcriptional dysregulation, metabolic reprogramming, subpopulation typing and clinical application, aiming to provide more CD8 + T cell-based therapeutic strategies for tumor.

Objective:To summarize the best evidence for the prevention and management of oral mucosal pressure injury (OMPI) in severe neurological patients with tracheal intubation.Methods:The clinical decisions, guidelines, expert consensus, evidence summary, systematic reviews, and clinical practice regarding the prevention and management of OMPI in severe neurological patients with tracheal intubation were searched in domestic and foreign databases, guideline websites, and professional association websites. The search period was from database establishment to May 30, 2023. Four researchers who undergone systematic evidence-based training conducted literature quality evaluation and evidence extraction.Results:A total of 15 articles were included, including three evidence summaries, three systematic reviews, two guidelines, three clinical practices, three expert consensus, and one clinical decision. A total of 27 pieces of best evidence were summarized from six aspects of risk assessment, oral mucosal assessment, oral nursing, tracheal intubation management, nutritional support, and organizational training.Conclusions:The best evidence for the prevention and management of OMPI in severe neurological patients with tracheal intubation summarized provides evidence-based evidence for medical and nursing staff to prevent and manage OMPI in severe neurological patients with tracheal intubation.

Objective:To explore risk factors of death in type A intramural hematoma (IMH) patients with conservative therapy and provide important information for clinical risks stratification and decisions-making.Methods:This retrospectively study enrolled 130 patients diagnosed with type A IMH in the first CT examination at Fuwai Hospital of Chinese Academy of Medical Sciences and only received conservative therapy between September 2009 and June 2018. Baseline clinical and CT characteristics were recorded. All patients enrolled were followed up. The endpoint was aortic disease-related death, patients were divided into endpoint group and non-endpoint group according to whether or not an endpoint event occurs. Difference between two groups of normally distributed continuous variables, non-normally distributed continuous variables and categorical variables were tested by independent sample t test, Mann-Whitney U test and chi-square test or Fisher′s exact test, respectively. Independent risk factors related to outcomes were assessed with Cox regression analysis and survival analysis. Results:In baseline CT data, the mean value of the maximum aortic diameter (MAD) was (49.2±6.9) mm, and the median value of the maximum hematoma thickness (MTH) was 11.0 (8.5, 13.2) mm. There were 56 and 30 patients with ulcer-like projection (ULP) and intramural blood pool (IBP), respectively, which including 36 patients with ULP of ascending aorta, 51 patients with pericardial effusion and 50 patients with pleural effusion. During a median follow-up time of 1 050 (242, 1 949) days, 26 patients experienced aortic disease-related death. Compared with non-endpoint group patients, patients who experienced aortic disease-related death showed older age and larger MAD( t=2.363, 3.640, P=0.020,<0.001), higher proportion of aortic atherosclerosis, ULP and pericardial effusion (χ 2=5.275, 6.596, 9.325, P=0.022, 0.010, 0.002).In Cox regression multivariate analysis shows that aortic atherosclerosis [hazard ratio (HR)=3.48, P=0.043], ULP (HR=2.66, P=0.019) and pericardial effusion (HR=2.49, P=0.030) were independent risk factors for aortic disease-related death. Conclusions:Aortic atherosclerosis, ULP and pericardial effusion are independent predictors of subsequent aortic disease-related death for type A IMH patients with conservative therapy, identifying these risk factors is helpful for further risk stratification and decisions-making.

Objective By employing surgically induced varicocele(VC)in SD rats and an apomorphine(APO)test,we screened rats with erectile dysfunction(ED)after VC and explored method to establish VC and ED models.Methods Sixty rats were randomly divided into Control,Sham,and Model groups with 20 rats in each group.Using the Turner method,we partially ligated the left renal vein to induce left VC three times.APO tests were conducted to screen rats with ED after inducing VC.The numbers of erections,genital grooming,and yawning were observed and recorded.The diameter of bilateral spermatic veins were measured.Both testises and kidneys were weighed.HE staining was used to observe pathological changes of penis and left testis.The success rate of modeling was calculated in the Model group.Results A VC and ED model was successfully established in 15 out of 20 rats in the Model group with a success rate of 75％.After modeling,the diameter of the left spermatic vein in the model group was increased significantly(P＜0.01)and was significantly larger than that before modeling(P＜0.01).The diameter of the right spermatic vein in the Model group was increased(P＜0.05)and higher(P＜0.05)than that before modeling.The weight of the left testis in the Model group was significantly decreased(P＜0.01)compared with that of the right testis.No significant difference in the bilateral kidney weights were observed between or within groups(P＜0.05).In the Model group,the numbers of erections,yawning,and genital grooming decreased significantly(P＜0.01)with the time of modeling.Pathological changes of the left testis and penis were significant in the Model group.Conclusions The Turner method increases the diameter of the spermatic vein in rats,causing testis injury and weight loss,and APO tests can be used to screen rats with ED after VC induction.The combination of the two method is suitable to establish an animal model of VC with an ED status similar to humans.