Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective Based on the clinical data and imaging manifestations of patients with ischemic stroke to establish a simple clinical prediction model that is used for identifying intracranial atherosclerotic stenosis-acute large vessel occlusion(ICAS-LVO in posterior circulation before surgery.Methods The clinical data of patients with acute large vessel occlusion(LVO in the posterior circulation,who received endovascular intervention at the First Affiliated Hospital of Nanjing Medical University of China from January 2019 to September 2022,were retrospectively analyzed.According to the intraoperative angiographic findings,the patients were divided into ICAS-LVO group and non-ICAS-LVO group.Univariate analysis and multivariate logistic regression analysis were used to analyze the patient's demographic characteristics,clinical history,imaging findings,and laboratory results,based on which a clinical prediction model for ICAS-LVO was established,and according to the relevant parameters a nomogram prediction model was plotted.Results A total of 110 patients with LVO in the posterior circulation who received endovascular treatment were included in the final analysis.In 51 patients(49.6％)the cause of vascular occlusion was the atherosclerotic stenosis of the intracranial arteries.Compared with non-ICAS-LVO group,in ICAS-LVO group the patients were younger,the incidence of atrial fibrillation was lower,and the level of plasma D-dimer was lower.Three factors,including atrial fibrillation,occlusion site and collateral circulation status,were finally screened out to establish the prediction model for ICAS-LVO.This model demonstrated acceptable calibration(Hosmer-Lemeshow test,P=0.562)and good discrimination ability(AUC=0.956;95％CI:0.906-0.986).Conclusion The clinical prediction model for ICAS-LVO,which is established on the three predictive factors(absence of atrial fibrillation,occlusion located at the V4 segment of the vertebral artery or at the proximal to mid segment of the basilar artery,and a favorable collateral circulation),carries high sensitivity and accuracy.This model can help neurointervention physicians to make early identification of ICAS-LVO and to promptly formulate vascular recanalization treatment strategies.

Objective To evaluate the clinical value of optic nerve sheath diameter(ONSD)measured on thin-slice CT scan in the diagnosis and prognostic assessment of cerebral venous sinus thrombosis(CVST).Methods The clinical data of patients with CVST,who were admitted to the First Affiliated Hospital of Nanjing Medical University of China to receive treatment from January 1,2016 to December 31,2022,were retrospectively analyzed.The difference in ONSD was compared between CVST patients and normal population,the postoperative changes in ONSD was analyzed.Results A total of 49 patients with CVST(CVST group)and 49 normal persons having no brain disorders(control group)were enrolled in this study.In CVST group,the preoperative ONSD was(5.33±0.50)mm,which was significantly higher than(4.40±0.40)mm in control group(P＜0.001),the postoperative ONSD remarkably decreased to(4.98±0.59)mm(P＜0.01).The difference value between postoperative ONSD and preoperative ONSD in the patients receiving pure anticoagulation treatment was not statistically significant different from that in the patients receiving endovascular treatment[(-0.43±0.22)mm vs.(-0.40±0.42)mm,P=0.84].The preoperative ONSD in the patients having intracranial hemorrhage and in the patients having no intracranial hemorrhage was(5.26±0.51)mm and(5.41±0.49)mm respectively(P=0.31),and the difference value between postoperative ONSD and preoperative ONSD was(-0.39±0.40)mm and(-0.45±0.25)mm respectively(P=0.66).At the three-month follow-up visit,the difference in ONSD between the patients having a good prognosis(mRS score being 0-2 points)and the patients having a poor prognosis was not statistically significant(P＞0.05).Conclusion ONSD that is measured on plain head CT scan can be used as a response indicator of elevated intracranial pressure in CVST patients,which can be used to monitor the changes in intracranial pressure before and after treatment,but its value in assessing the curative efficacy of different therapeutic methods needs to be further explored.

OBJECTIVE To explore the mechanism of action of Fushao Diqin Decoction in the treatment of colorectal cancer.METHODS In vitro cell experiments were conducted using Fushao Diqin Decoction to treat colorectal cancer CT-26 cells,and the cell proliferation and migration abilities were detected.Flow cytometry was used to detect the levels of reactive oxygen species(ROS)in colorectal cancer CT-26 cells,as well as the levels of iron ions(Fe2+),malondialdehyde(MDA),and the activity of su-peroxide dismutase(SOD).PCR Array and Western blot methods were used to analyze and verify the differential gene expression of ferroptosis.Balb/c mice were randomly divided into a blank control group,a model group,an oxaliplatin group(1.5 mg·kg-1·d-1),a low-dose group of Fushao Diqin Decoction(4.49 g·kg-1·d-1),a medium dose group of Fushao Diqin Decoction(8.97 g·kg-1·d-1),and a high-dose group of Fushao Diqin Decoction(17.94 g·kg-1·d-1)for in vivo animal experi-ments.The effects of Fushao Diqin Decoction on Fe2+,ROS,MDA levels,SOD activity,and Nrf2,Keap1,SLC7A11 and GPX4 ex-pression levels in mouse tumor tissues were tested.RESULTS In vitro cell experiments showed that compared with the blank control group,Fushao Diqin Decoction significantly inhibited the proliferation and migration of colorectal cancer CT-26 cells in a dose-de-pendent manner.Fushao Diqin Decoction could increase the Fe2+content(P＜0.05)and ROS level(P＜0.01)in colorectal cancer CT-26 cells,increase the MDA level in CT-26 cells of colorectal cancer(P＜0.01)and significantly reduce SOD activity(P＜0.01).Iron death PCR array analysis found that compared with the blank control group,after intervention with Fushao Diqin Decoc-tion,the expression of genes GPX4 and SLC7A11 was significantly downregulated,while the expression of GSTA1,HMOX1,Ca9,Chac1,Keap1,Sqstm1,NOX1,FTH1,Tfr1,SAT2,Pparg,and Hamp was significantly upregulated.Western blot analysis revealed that after intervention with Fushao Diqin Decoction,the expression of Keap1 protein was upregulated(P＜0.01),while the expression of Nrf2,SLC7A11,and GPX4 proteins was downregulated(P＜0.01)in colorectal cancer CT-26 cells.The results of in vivo animal experiments showed that Fushao Diqin Decoction significantly inhibited the growth of subcutaneous transplanted tumors in mice(P＜0.05),increased the degree of tumor tissue necrosis,and levels of Fe2+,ROS,and MDA(P＜0.05,P＜0.01),decreased SOD ac-tivity(P＜0.01)and upregulated Keap1 protein expression(P＜0.01),while downregulated Nrf2,SLC7A11,and GPX4 protein ex-pression(P＜0.01).CONCLUSION Fushao Diqin Decoction has an anti-colorectal cancer effect and may promote ferroptosis in colorectal cancer cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway to exert its anti-colorectal cancer effect.

Gastric cancer (GC) is one of the common malignant tumors globally. Its characteristics of high morbidity and mortality, high metastasis, low early diagnosis rate, low radical resection rate and low 5-year survival rate have seriously affected clinical treatment and patients’ prognosis. Circulating tumor cells (CTCs) are cancer cells that leave a solid tumor lesion and enter the bloodstream. Its diffusion and migration are important reasons for distant metastasis. In some solid tumors, enumeration of CTC has served as surrogate markers for overall survival (OS), progression-free survival (PFS) and chemotherapy effectiveness, and risk factors of relapse. Unfortunately, the study of CTC in GC is not sufficient. In this review, we collected relevant literatures and described the clinical significance of CTC for the patients with GC, especially advanced gastric cancer (AGC), including the biology, detection methods, and clinical applications of CTC, discussed the challenges and the future prospects in this field.

【Objective】 To explore pain and collapse mechanisms in fosteonecrosis of the femoral head (ONFH) with bone marrow edema (BME). 【Methods】 ONFH patients at ARCO Ⅲ stage who underwent total hip arthroplasty in the First Affiliated Hospital of Guangzhou University of Chinese Medicine were enrolled; the femoral head samples, clinical and imaging data were collected. These patients were divided into BME group and non-BME group according to the MR data in one week preoperative. Hematoxylin-eosin and Sirius red staining were performed to observe the morphological changes in bone tissue of femoral head specimens. Western blotting and qPCR were used to semi-quantitatively analyze the expression levels of CTSK, RANKL, and Netrin-1 proteins and mRNA in different regions of the bone tissue. 【Results】 Clinical and imaging data showed that ONFH patients with BME had significantly higher scores of VAS than ONFH patients without BME. Hematoxylin-eosin staining showed that bone structure disorder and a large number of empty bone lacunae were found in the necrotic areas in both groups, but there exited significant granulation tissue in the BME group, and spindle-shaped fibroblastic cells and inflammatory cells aggregated in the repaired region. Sirius red staining revealed the necrotic and sclerotic areas were accumulated with many collagenous fiber in the BME group. The results of Western blotting and qPCR showed that Netrin-1 expressions in the necrotic, sclerotic and health areas in the BME group were higher than those in the non-BME group (P<0.05), while osteoclast related proteins and mRNA expressions of the necrotic and sclerotic areas in the BME group was higher than those in the non-BME group (P<0.05). 【Conclusion】 All these findings indicated that hip pain was positively correlated with femoral head necrosis with BME, hyperactive osteoclasts participated in the femoral head collapse with BME, and the upregulated expression of Netrin-1 mediated the pain mechanism.

Objective:To study the relationship between gastric fundus size and postoperative gastroparesis and to find effective ways to prevent postoperative gastroparesis in high-risk patients.Methods:We retrospectively reviewed the clinical data of 276 gastric cancer patients undergoing radical gastrectomy from 2015 to 2016. The gastric fundus volume/total gastric volume (FV/TV) ratio was measured by computed tomography (CT) and comparative study between the gastroparesis group and the non-gastroparesis group was carried out in terms of postoperative gastroparesis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance. Single-factor and multiple-factor analyses were performed to filter clinically significant predictive factors of gastroparesis. Then, we increased the sample size to 304 patients whose FV/TV ratio was >19.4%. The different surgical methods and perioperative management of these patients were analysed. The chi-square test and logistic regression analysis were performed to identify effective independent factors for preventing gastroparesis.Results:The FV/TV ratio in the gastroparesis group was significantly higher than that in the non-gastroparesis group ( P<0.05). A cut-off value of 19.4% was selected by ROC curve analysis, at which the FV/TV ratio had a sensitivity of 76.2% and a specificity of 53.7%. In 304 patients in the second retrospective study, the incidence of gastroparesis was 9.2%. Gastroparesis was significantly reduced in patients with residual gastric size <1/3 ( P<0.05) and early postoperative gastrointestinal decompression ( P<0.05). Conclusions:The FV/TV ratio can effectively predict the risk of postoperative gastroparesis preoperatively. Small residual stomach and early postoperative gastrointestinal decompression are effective measures to prevent gastroparesis in high-risk patients.

Objective:To visualize the research hot spots and frontiers of non-surgical treatments for idiopathic scoliosis (IS) based on CiteSpace.Methods:The Web of Science Core Database and China National Knowledge Infrastructure from 1990 to 2020 were searched for studies of non-surgical treatments of idiopathic scoliosis. The time, distributions of nations, institutions, academic disciplines and keywords of literature were analyzed. With CiteSpace 5.7.R4 and Excel 2017, the visualized knowledge graphs and the data tables were generated.Results:A total of 822 studies including 548 articles in English and 274 articles in Chinese were retrieved, including 378 articles published during 2015—2020. The top three nations with higher number of published articles were USA (114 studies), Canada (77 studies) and China (68 studies). Studies covered 33 disciplines, including rehabilitation, engineering and orthopedics, and the betweenness centrality of rehabilitation medicine was the highest (0.59). The non-surgical treatment research was focused on adolescents (187 studies) and brace treatment (116 studies). From 1990 to 2014, the non-surgical treatment of IS mainly focused on the brace treatment (70.4%,69/98) in domestic studies. After 2014, comprehensive treatments such as exercise therapy and manual therapy gradually became the research trend in this field (61.3%,92/150). Research hotspots included different forms of brace treatment (betweenness centrality: 0.31), exercise (6 studies), manual therapy (3 studies), guide of medicine (2 studies), acupuncture therapy (2 studies) of non-surgical treatments. Among top 30 research institutions for domestic publication of Chinese literature, there were 22 tertiary hospitals, 1 secondary hospital, 5 schools, 1 comprehensive rehabilitation service organization, and 1 community health service center.Conclusion:The research content of non-surgical treatment for idiopathic scoliosis tends to be diversified, comprehensive treatment of exercise therapy, brace therapy, and manual therapy are currently the main research hotspots.

With the rapid development of medical imaging technology, there are many corresponding kinds of medical images. The traditional teaching and examination mode based on typical images cannot meet the needs of medical imaging teaching. Therefore, we took the post competence of medical imaging students as the guidance, integrated multidisciplinary medical image resources, and established the human-computer dialogue teaching and examination system for medical images. The system was applied to medical imaging teaching and examination, achieving the standardization and clinical simulation of teaching and examination, and effectively improving the post competence of students.

Objective: To evaluate the dietary exposure to deoxynivalenol (DON) from cereals and health risk in Chinese residents in different regions. Methods: The data of DON concentration in cereals was derived from the national food safety risk surveillance from 2010 to 2017, with 15 422 samples of cereals included. China was roughly divided into north part and south part, along with the Qinling Mountains-Huaihe River line. Sample size of each type of cereals, i.e. wheat flour, maize meal, oats and rice was 4 948, 696, 626, 1 006 in the north, while 5 648, 1 068, 266, 1 164 in the south. The data of cereals consumption was derived from China National Nutrition and Health Survey in 2002 and 68 335 respondents aged 3 and above, with 34 234 from the north and 34 101 from the south, were included. Simple distribution model was applied for calculation and comparison of the dietary exposure to DON from cereals in northern and southern residents based on individual consumption of cereals, body weight and average DON concentration in each type of cereals. Results: Average DON concentration in wheat flour, maize meal, oats, and rice sampled in northern China were 235.4, 121.6, 7.0 and 4.6 μg/kg, respectively, while 239.1, 124.3, 29.0 and 15.5 μg/kg in cereals sampled in southern China. The average DON exposure from cereals in surveyed Chinese inhabitants was 0.78 μg/(kg·d). Among them, the DON exposure of northern residents was higher than that of southern residents (P<0.001), and the average exposures were 1.15 and 0.41 μg/(kg·d), respectively. A total of 49.2% of northern residents exceeded provisional maximum tolerable daily intake for DON exposure from cereals, which was much higher than that of southern residents (8.6%) (P<0.001). Wheat-based food products were the main source of DON exposure, with a contribution rate of 96.5% in the north and 68.3% in the south. Average DON exposure was the highest in the 3-6 years [2.12 μg/(kg·d) for children in north and 0.73 μg/(kg·d) in south]. Conclusion Exposure to DON from cereals in northern residents of China was considerably high, with a certain health risk. Northern children aged 3 to 6 exposed even more DON and needed significant attention.