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.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To explore the tumor microenvironment (TME) module associated with pancreatic ductal adenocarcinoma (PDAC) and identify prognostic biomarkers and potential immunotherapeutic targets.Methods:The genetic expression profile data were collected and selected from a dataset of 142 PDAC patients in The Cancer Genome Altas (TCGA) database and 2 microarray datasets (GSE2150, GSE62452) of 168 PDAC patients in Gene Expression Omnibus (GEO) database, and the cell type enrichment analysis of PDAC gene expression data was analyzed by xCell network tool. According to the median cell enrichment score, 142 patients from TCGA were divided into high score group and low score group, and the cell types with prognostic value were determined by univariate survival analysis and validated by GEO datasets. According to the cell type, the differential expression gene analysis and univariate survival analysis were performed to determine the prognosis related differential expression genes (DEGs), and the prognostic DEGs were analyzed by function enrichment analysis and protein-protein interaction (PPI) network analysis. At the same time, GEO dataset was used to verify the prognosis related DEGs of TCGA datasets. Finally, TISIDB database was searched for the common DEGs of TCGA and GEO database, and its correlation with immune system was analyzed.Results:Cell type enrichment analysis showed that Th1 cell and keratinocyte had the same prognostic value in both TCGA and GEO dataset; the overall survival rate of patients with high score was lower than that of those with low score, and the differences were statistically significant (all P values <0.05). 216 prognosis related DEGs were identified, and the results of functional enrichment showed that 9 of the 21 biological process items were closely related to the immune process, and 4 of the 5 KEGG (Kyoto Encyclopedia Of Genes and Genomes) pathways were closely related to the immune process. Through PPI network analysis, CCR7, CD 27, CD 5, CXCL13, ZAP70, MS4A1 and CCL19 were proved to be possibly closely associated with central genes. Through the validation of GEO datasets, there were 15 DEGs with similar prognostic value in GEO and TCGA datasets, which was searched in TISIDB dataset, and the result showed that GIMAP7 was closely related with the immune process of PDAC. Conclusions:A group of 216 TME genes and 7 central genes related to the prognosis of PDAC were identified, and 5 potential targets for immunotherapy of PDAC were provided, including CCR7, CCL19, CD 27, CXCL13 and GIMAP7.

Objective:To evaluate alterations of periventricular pseudocysts (PVPC) on MRI before and after birth, and to assess the prognosis.Methods:We retrospectively analyzed the data of 67 cases that were diagnosed with PVPC on prenatal MRI, of which 24 cases were lost to follow-up, 2 died after birth. A total of 41 surviving fetuses were included in this prognosis study. The gestational ages in this group were between 23 and 39 weeks, with an average of (33±3) weeks.All the subjects underwent brain MRI examinations and Gesell Developmental Scale (GDS) testing between 0-3 years of age. According to the location of cysts and with or without other intracranial and extracranial malformations (dilated ventricles orcerebella medulla, hypoxic-ischemic encephalopathy, TORCH virus infection, corporal hypoplasia, chromosomal malformations and nodular sclerosis) , the patients were divided into four groups: isolated connatal cysts, connatal cysts with additional findings,isolated subependymal pseudocysts, and subependymal pseudocysts with additional findings.The MR images were independently reviewed by two radiologists blinded to the clinical information. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two reviewers.Chi-square test was used to compare the location of cysts (single/bilateral), the number of cyst cavities (single/multi-chamber), and other abnormalities in the connatal cyst group and subependymal cyst group. The mean anteroposterior diameter and mean height of cysts between the connatal cyst group and subependymal cyst group were compared by independent sample t-test.The ANOVA test was used to compare the differences in GDS outcomes among the groups. Multiple comparisons were conducted using the LSD test. Results:Inter-observer agreements between the two radiologists were good for the collected data (all ICC>0.75). Eleven isolated connatal cysts and 7 connatal cysts with additional findings became smaller or disappeared, and all had good prognosis. Of the 14 isolated subependymal cysts, 12 became smaller or disappeared, 2 had no change in size, and 13 had good prognosis. The subependymal cysts with additional findings group included 9 cases: 6 became smaller or disappeared, only 3 showed no apparent changes, and 7 had an abnormal outcome. Subependymal cysts with additional findings were significantly reduced and patients demonstrated significant differences compared with the those with isolated subependymal cysts in the development quotients (DQ) of adaptability, large movements, fine movements, personal social interaction, and language DQ ( P all<0.05). DQ between patients with isolated connatal cysts and isolated subependymal cysts was comparable ( P all>0.05). When associated with additional findings, connatal cysts and subependymal cysts could induce significant different DQ outcome ( P all<0.05). Conclusions:Isolated PVPC usually become smaller or disappeared and have a benign presentation after birth, whereas patients with subependymal cysts with additional findings usually have a poor prognosis. Connatal cysts usually have a good prognosis.

Objective:To investigate the correlation of age with diffusion tensor imaging (DTI) values as fractional anisotropy (FA), apparent diffusion coefficient (ADC) and contrast to noise ratio (CNR) of three-dimensional nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation imaging (3D SHINKEI) of the brachial plexus in normal adults.Methods:A total of 54 adult healthy volunteers and 6 patients with Guillain-Barre syndrome were prospectively enrolled from October 2018 to April 2019. Healthy volunteers were divided into 3 groups according to age as 21-40 years old group ( n=20), 41-60 years old group ( n=20), and ≥61 years old group ( n=14). All of them underwent MRI examination of the brachial plexus, including DTI and 3D SHINKEI sequences. The average FA and ADC values of the brachial plexus were measured and calculated through the fusion of DTI and 3D SHINKEI by 2 physicians independently. The contrast to noise ratio (CNR) of brachial plexus nerve was measured in 3D SHINKEI sequence images. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two physicians. A simple linear regression model and Pearson correlation analysis were used to detect the correlation between FA, ADC, CNR and age. One-way analysis of variance was used to compare the differences of FA, ADC and CNR in different age groups. The FA and ADC values in different genders were compared by independent sample t-test. Results:Inter-observer agreements of the 2 physicians were good for FA and ADC values with ICC values of 0.811 and 0.901, respectively. For different groups, FA values were 0.397±0.023, 0.368±0.023, and 0.334±0.018 and ADC values were (1.376±0.072) × 10 -3 mm 2/s, (1.466±0.086) × 10 -3 mm 2/s, (1.486±0.080) × 10 -3 mm 2/s, for 21-40, 41-60, and ≥61 years old groups, respectively with statistical significant difference ( F=25.311, P<0.001; F=9.948, P<0.001). The CNR of the brachial plexus were 510.583±192.846, 502.581±128.821, and 426.782±113.648 for 21-40, 41-60, and ≥61 years old group without statistical difference ( F=1.429, P=0.249). The FA value of brachial plexus was highly negatively correlated with age ( r=-0.745, P<0.001), while the ADC value was moderately positively correlated with age ( r=0.596, P<0.001). The CNR of 3D SHINKEI sequence was negatively correlated with age ( r=-0.292, P=0.033). There was no statistically significant difference in brachial plexus FA and ADC values between male and female subjects ( t=1.496, P=0.141; t=-1.557, P=0.126). The FA value of Guillain-Barre syndrome patients was lower than that of healthy volanteers in the same age group ( t=6.129, P<0.001), and the ADC value had no statistical diference ( t=-1.335, P=0.186). Conclusion:The values of FA, ADC and CNR of brachial plexus in normal adults change with age. Among them, FA value is more significant.

Objective:To summarize the different teaching models and their effects in evidence-based medicine at home and abroad by qualitative method and systematic review.Methods:We searched the following databases (from inception to 13 May, 2019): PubMed, Embase, Proquest, Cochrane, Web of Science database and the Chinese databases (CNKI, Wanfang, SinoMed and VIP). To assess data strength and validity, risk of bias assessments were undertaken.Results:A total of 52 literatures were included in this study, including 21 Chinese-language literature and 31 English-language literature. PBL teaching model, mixed teaching model and workshop teaching model were the three teaching models with the largest number of studies in 20 teaching models.Conclusion:The evidence-based medicine teaching effect was closely related to the teaching models, so it is necessary to explore more suitable teaching models for the evidence-based medicine to improve the teaching effects.

To develop an intelligent lower limb rehabilitation instrument which could realize the quantification and visualization of lower limbs' raising angle and frequency, using the smart client to realize the remote control, autonomous data acquisition and the establishment of database. Doctors had the access to the database in order to adjust the rehabilitation program in time to meet the individual requirement. We realized the design of intelligent lower limb instrument based on the Andriod smartphone, which is suitable for clinical and family use.
Computers ; Databases, Factual ; Humans ; Leg ; Mobile Applications ; Rehabilitation ; instrumentation ; Smartphone

Objective: To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors. Methods: A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017. Results: The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival. Conclusions Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.

Objective To study the effects of Androsace umbellata extract on bone wound healing in rats.Methods A total of 32 rats were selected,and the rat femur bone trauma model was established.The Androsace umbellata was administrated to rats in treatment groups (including high-dose Androsace umbellata group and low-dose Androsace umbellata group,8 rats in each group)continuously for 10 days,while rats in the fake operation control group (8 rats)and bone trauma model group (8 rats) were treated with corresponding volume of solvent by body weight.The growth of body weight and wound healing of rats were recorded.The serum levels of calcium and phosphorus,activity of alkaline phosphatase (ALP),bone density and bone biomechanics were examined.The X-ray photograph was carried out to observe the effects of Androsace umbellata on bone wound healing,Results Compared with the bone trauma model group,serum levels of calcium and phosphorus,calcium-phosphorus product and activity of ALP were significantly increased in treatment groups,there were statistically significant differences (P＜0.05).Compared with the bone trauma model group,bone density of trauma place in the high-dose Androsace umbellata group was significantly decreased (P＜0.05),bending energy in the low-dose Androsace umbellata group was increased (P＜0.05),while no statistically significant difference was found in the other skeletal biomechanical properties (P＞0.05).The results of X-ray films indicated that the treatment groups shown better effects on bone wound healing compared with the bone trauma model group.Conclusion Androsace umbellata extract could effectively promote bone wound healing in rats.

Objective: To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes. Methods: Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed. Results: The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01). Conclusions AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.