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:To analyze the application value of color Doppler ultrasound,microribonucleic acid-19a(miR-19a)and miR-210 in carotid artery stenosis.Methods:A total of 102 patients with carotid artery stenosis who were diagnosed and treated in Cangzhou People's Hospital from October 2020 to October 2022 were selected as the research group,and 102 health persons who underwent color Doppler ultrasound of physical examination in hospital at the same period were selected as the health control group.Both two groups underwent color Doppler ultrasound examination and digital subtraction angiography(DSA)within one week after admitted to hospital.The miR-19a and miR-210 between the two groups were compared,and the miR-19a and miR-210 of patients with different stenosis degrees of research group also were compared.And then,the diagnostic values of color Doppler,miR-19a,miR-210 and the combination of them were analyzed in diagnosing carotid artery stenosis.Results:The results of color Doppler ultrasound in detecting common carotid artery 102 patients of research group indicated that 15 cases were normal,and 15 cases occurred mild stenosis,and 21 cases occurred moderate stenosis,and 21 cases occurred severe stenosis and 33 cases occurred complete occlusion.The miR-19a of the research group was significantly higher than that of the health control group,and the miR-210 of the research group was significantly lower than that of the health control group(t=10.755,-5.903,P<0.05).The miR-19a results of the research group indicated that the miR-19a of mild stenosisthat of moderate stenosis>severe stenosis>complete occlusion,and the differences were statistical significant(F=160.399,147.462,P<0.05),respectively.The receiver operating characteristic(ROC)curve analysis showed that the area under curve(AUC)values of color Doppler ultrasound,miR-19a,miR-210 and combined diagnosis of them for carotid artery stenosis were respectively 0.892,0.842,0.729 and 0.978,and the sensitivity and specificity of the combined diagnosis were respectively 97.1%and 95.1%.Conclusion:The combined diagnosis of color Doppler ultrasound,miR-19a and miR-210 has higher diagnostic value for carotid artery stenosis.

Objective:To investigate clinical value of real time three-dimensional transesophageal echocardiography(RT-3D-TEE)in assessing patients with mitral valve prolapse(MVP)combined with mitral regurgitation(MR).Methods:The clinical data of 99 patients with MVP that combined with MR,who admitted to CANGZHOU People's Hospital from February 2020 to October 2023 and were confirmed by RT-3D-TEE,were retrospectively analyzed.According to two dimensional(2D)comprehensive method,they were divided into mild MR group(43 cases)and moderate-severe MR group(56 cases)as the degree of disease condition.The RT-3D-TEE parameters of the two groups were compared.The combined predictive indexes of RT-3D-TEE parameters were obtained by logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the values of single and combined RT-3D-TEE parameter in assessing the degree of disease condition of MVP patients with MR.Result:The anterolateral to posteromedial diameter(DAIPm),anterior-to-posterior diameter(DAP),nonplanarity angle(θNPA),annulus area in 3D(A3D),annulus perimeter(AP),total valve leaflet area of mild MR group were respectively(3.20±0.39)cm,(2.82±0.26)cm and(115.77±12.60)°,(6.90±1.28)cm2,(9.36±0.83)cm and(7.71±1.46)cm2,which were significantly less than those[(3.66±0.36)cm,(3.24±0.40)cm,(125.41±13.23)°,(7.99±1.59)cm2,(10.47±1.15)cm and(9.38±1.81)cm2]of moderate-severe MR group,respectively,and the differences of these indicators between two groups were significant(t=6.092,5.965,3.670,3.680,5.333,4.929,P＜0.05).The involution-index of mild group was(26.39±4.39),which was significantly larger than that(22.94±3.65)of moderate-severe MR group(t=4.264,P＜0.05).There were no significant differences in valve annulus height(H),angle of anterior leaflet(θAnt)and angle of posterior leaflet(θPost)between the two groups(P＞0.05).The area under curve(AUC)values of ROC curve of DAIPm,DAP,θNPA,involution-index,A3D,AP and Total valve leaflet area were respectively 0.818,0.831,0.712,0.737,0.704,0.806 and 0.765 in assessing the disease degree of MVP patients with MR.The AUC value of combined detection of them was 0.990.Conclusion:DAIPm,DAP,θNPA,involution-index,A3D,AP and Total valve leaflet area of RT-3D-TEE parameters had a certain value in assessing the disease degree of MVP patients with MR,and the assessment value of combined detection is higher.

Objective To investigate whether decursin(Dec) could inhibit EC109 cells proliferation by suppression of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in human esophageal squamous cell carcinoma.Methods The EC109 cells were treated with Dec(20,40,and 80 pmmol/L) for48 h.The cell viability was evaluated by MTT;the apoptotic cells was labelled by TUNEL;the mitochondrial oxidative stress level was detected by fluorescent staining;and western blotting was used to analyze the proteins of JAK2/STAT3 signaling and apoptosis in EC109 cells,respectively.After co-application of JAK2 / STAT3 antagonist(AG490),the inhibitory ability of Dec to EC109 was observed from the in vivo and in vitro levels.Results Compared to the control group,different concentrations of Dec dose-dependently down-regulated expressions of p-JAK2 [(55.89 ± 6.04) ％] and p-STAT3 [(45.27 ± 8.65) ％],repressed EC109 cell activity(0.43 ± 0.078),increased apoptotic rate[(35.31 ± 8.41)％],reduced MMP levels[(37.23 ± 6.89)％],promoted reactive oxygen species(ROS) [(231.81 ± 19.63)％],decreased glutathione (GSH) activity [(46.78 ± 6.91)％,P＜0.05].However,Dec did not significantly affect the activity of the normal esophageal epithelium HET-1A cells(P ＞0.05).Meanwhile,Dec obviously leaded to reduction of Bcl2,increment of Bax,and augment of Caspase-3 cleavage (P ＜0.05).Additionally,the inhibitory effect of Dec on EC109 was specifically intensified after co-application of AG490 in vivo and in vitro levels(P ＜0.05).Conclusion Dec can fight against human esophageal squamous cell carcinoma in vitro and in vivo via activation of mitochondrial oxidative stress-induced apoptosis which was mediated by JAK2/STAT3 pathway.

Alzheimer′s disease(AD)is a chronic progressive neurodegenerative disease in the elderly,which causes heavy burden for the society and family.The current drugs could only improve the cognitive symptoms in the short term,but could not reverse or stop the disease progression.In view of the complexity of AD,multi-targe-ted drugs could be a potential strategy for the treatment of AD.Flavonoids,widely exising in the natural world, have multiple pharmacological activities.This paper summarizes flavonoids as promising multi-targeted anti-AD candidates according to the reported references previonsly published,which could provide important evidences in the development of anti-AD durgs.

Objective To understand current situation of full-time healthcare-associated infection(HAI)manage-ment staff in hospitals in Xianyang,explore the causes of instability of HAI management team.Methods Stratified random sampling method was adopted,hospitals were divided into secondary and tertiary levels,then numbered ac-cording to different levels,surveyed hospitals were selected randomly,general condition,professionals,and causes of instability of 52 selected full-time HAI management staff members in 29 secondary and above hospitals in Xian-yang were surveyed.Results Full-time HAI management staff were mainly women,accounting for 89.13%;54.35% of staff were aged 30-50 years;47.83% had bachelor degree and above;41.30% had intermediate profes-sional titles;65.22% were nurses;91.30% engaged in HAI management for <9 years;HAI management staff were statistically different in age and education level(both P<0.05).63.04% of full-time HAI management staff engaged in nursing before engaging in HAI management work;63.04% engaged in HAI management work accord-ing to administrative arrangement,the top three causes for instability of HAI management team were heavy work-load(91.30%),lacking enough attention of leaders(78.26%),and low pay(63.04%).Conclusion Structure of HAI management full-time staff in hospitals in Xianyang is irrational,the main causes for unstable management team is heavy workload,insufficient attention paid by leaders,and low pay.

Objective To investigate the changes of cortical thickness and relative resting state functional connectivity in patients with generalized anxiety disorder (GAD).Methods The present study analyzed structural and eyes-open resting state functional MRI were performed in 21 patients with GAD and 22 matched healthy controls.Cortical thickness was estimated with FreeSurfer.The structurally altered regions were defined as region of interest (ROI) to analyze functional connectivity (FC) using resting state functional MRI data by DPABI.Results Cortical thickness of patients with GAD were increased in right rostral middle frontal gyrus (rMFG;MNI:x =27.9,y =53.4,z =-11.1;size:241.93 mm2;FDR corrected,P ＜ 0.1) and right inferior temporal gyrus (IGT;MNI:x =49.7,y =-57.8,z =-8.7;size:138.93 mm2;FDR corrected,P＜0.1) compared with healthy controls.FC between right rMFG and right superior/middle occipital gyrus as well as well as FC between rMFG and right precentral gyrus showed decreased in patients with GAD compared with healthy controls(AlphaSim corrected,P＜0.05).FC between right rMFG and right angular gyrus showed increased in patients with GAD compared with healthy control (AlphaSim corrected,P＜0.05).Conclusion The rMFG may play an important role in the pathophysiology of GAD,which can be used as an stimuli target in physicotherapeutics to improve anxiety symptoms.

Objective: To investigate blood-borne occupational exposure and related protection in the medical staff of a traditional Chinese medicine hospital, and to provide a reference for reducing the risk of blood-borne occupational exposure. Methods: Forty-eight medical workers with blood-borne occupational exposure in 2015 were selected to analyze the incidence of blood-borne occupational exposure, influencing factors, operations that caused blood-borne occupational exposure, pathogens, and occupational protection. Results: The incidence rate of blood-borne occupational exposure in the medical staff of the traditional Chinese medicine hospital in 2015 was 3.30% (48/1 455) , and the frequency was 0.04 time/person/year. The workers with blood-borne occupational exposure were mostly nurses, females, workers aged <30 years, workers with <5 working years, and workers with a junior professional title. There was a significant difference in the incidence rate of blood-borne occupational exposure between workers with different ages and working years. The main way of blood-borne occupational exposure was sharp injury (96.08%) . The main operations that caused blood-borne occupational exposure were covering or separating the syringe needle after injection and disposing used sharp instruments. The main exposure site was the hand (96.08%) , with the thumb and index finger for the left hand and the middle finger and index finger for the right hand; there was no significant difference in the exposure site distribution between the two hands (P<0.05) . The main pathogen that caused blood-borne occupational exposure was hepatitis B virus (68.96%) . The rate of correct local treatment for blood-borne occupational exposure was 88.24%. The rate of prophylactic medication was 74.51%, and hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine was the main way, followed by HBIG. In all workers with blood-borne occupational exposure, 62.74% did not wear gloves. Conclusion The medical workers with few working years have a high risk of blood-borne occupational exposure, so the training on protection against blood-borne occupational exposure should be strengthened to reduce the risk of blood-borne occupational exposure and infection.

BACKGROUND AND OBJECTIVEPhosphatase of regenerating liver-3 (PRL-3) is a newly identified protein-tyrosine phosphatase, which belongs to phosphatase of regenerating liver family, and plays a role in promoting tumor metastasis; Ras homologue C (RhoC) belongs to Rho subfamily of small-molecule G protein superfamily. However, the mechanisms of PRL-3 and RhoC are unknown. The aim of this study is to investigate the expressions of PRL-3 and RhoC proteins and their correlation to invasion and metastasis of non-small cell lung cancer (NSCLC), which may provide experiment evidence of the mechanism of PRL-3 in tumorigenesis and tumor-development.

METHODSImmunohistochemical staining was used to detect the expressions of PRL-3 and RhoC in NSCLC in 92 cases, and statistical methods were used to analyse statistical significances of their expressions in different groups and their correlation.

RESULTSThe positive rates of PRL-3 and RhoC expressions in NSCLC were 69.6% (64/92) and 73.9% (68/92), respectively, and the expressions of PRL-3 and RhoC were closely correlated with TNM stage and lymphatic metastasis and pleural metastasis (P < 0.01), and they were correlated with each other (r = 0.754, P < 0.001).

CONCLUSIONThe expressions of PRL-3 and RhoC are higher in the higher TNM stage and lymphatic metastasis and pleural metastasis cases, and closely correlate with each other in NSCLC, which suggests that PRL-3 and RhoC might be in the same signal pathway and PRL-3 might promote the distant metastasis of cancer cell by RhoC and downstream factors.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; chemistry ; pathology ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; chemistry ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Proteins ; analysis ; genetics ; physiology ; Neoplasm Staging ; Protein Tyrosine Phosphatases ; analysis ; genetics ; physiology ; rho GTP-Binding Proteins ; analysis ; genetics ; physiology ; rhoC GTP-Binding Protein

BACKGROUND AND OBJECTIVEAs a barrier to metastases, cells normally undergo apoptosis after they lose contact with their extra cellular matrix (ECM). This process has been termed "anoikis". Tumour cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site while traveling through the lymphatic and circulatory systems. This "anoikis resistance" is considered the first step to tumor metastases. The aim of this study was to screen metastasis-associated genes from anoikis resistant and adherent growth A549 lung cancer cell by Human Genome Array.

METHODSEstablish anoikis resistant A549 lung cancer cell lines by using poly-hydroxyethyl methacrylate resin processed petri dishes, which causes cell free from adherent. The different expressed gene between anoikis resistant A549 cell and adherent growth A549 cell was tested using human V2.0 whole-genome oligonucleotide microarray, a product of Capitalbio Corporation, Beijing. Screen metastasis-associated genes.

RESULTS745 different expressed genes were screened, including 63 highly metastasis-associated genes.

CONCLUSIONThe successfully established anoikis resistant A549 cell lines and screened different expressed genes provide us basis for further research on metastasis of lung cancer.

Anoikis ; genetics ; physiology ; Cell Line, Tumor ; Flow Cytometry ; Gene Expression Profiling ; Genome, Human ; genetics ; Humans ; Lung Neoplasms ; genetics ; Oligonucleotide Array Sequence Analysis