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.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.

Objective:Mycoplasma genitalium (Mg) is an opportunity pathogenic microorganism mainly transmitted through sexual contact. In recent years, scholars have paid more attention to Mg infection and pathogenicity. This study was aimed to understand the condition of Mg in the genitourinary tract of different populations in China and provide evidence for further study of its pathogenic characteristics. Methods:Cross-section studies of Mg infection in the Chinese community were searched by China National Knowledge Infrastructure (CNKI), Wanfang digital database, SinoMed, Pubmed, and Web of Science from database construction to March 10 th, 2020. Studies were sifted and screened independently by two evaluators based on inclusion and exclusion criteria, and Meta-analysis was conducted with R 1.1.463. If I 2≤50%, the fixed-effect model should be adopted, if I 2>50%, the random effect model should be adopted, and through subgroup analysis, the source of heterogeneity should be found out as far as possible. Results:A total of 47 research articles were included in this article, all of which were medium and high-quality articles. There was no obvious publication bias, and the results were more reliable. The research contained 19 provinces and Hong Kong Special administrative region, including 519 healthy people, 10 504 patients from clinics or hospitals of sexual transmitted disease (STD), 3 200 on Gynecology and 1 624 on Urology, 1 082 patients with men who have sex with men(MSM), 1 842 patients with Female sex worker(FSW), and 3 691 patients with HIV/AIDS. The infection rate of Mg in the genitourinary tract of the healthy population was 0.94% (95% CI: 0.07%-2.78%), the infection rate of Mg was 11.58% (95% CI: 8.57%-14.97%), 15.22% (95% CI: 7.99%-24.27%), 7.32% (95% CI: 4.24%-11.16%) among patients from clinics or hospitals of STD, gynecology and urology respectively. The infection rate of MSM was 9.70% (95% CI: 3.06%-19.52%),the infection rate of FSW was 13.49% (95% CI: 11.97%-15.08%). The infection rate of Mg among HIV infected patients was 20.46% (95% CI: 13.67%-28.22%). Conclusions:The infection rate of Mg in a healthy population was low. Mg infection rate in the genitourinary tract of other groups was still higher, which is worthy of further attention.

Objective:To evaluate the association of hyperuricemia with the risk for chronic kidney disease (CKD) in community adults.Methods:A community-based follow-up study comprising of 7 276 adults aged 20-74 years who attended the natural population cohort in Eastern China and had no CKD at baseline survey was performed in the Songjiang district, Shanghai. CKD was diagnosed according to the National Kidney Foundation Practice Guidelines for Chronic Kidney Disease criteria. Hyperuricemia was defined as serum uric acid level >420 μmol/L for men and >360 μmol/L for women. Cox proportional hazards model was used to examine the association of hyperuricemia with the risk for CKD.Results:During a median follow-up period of 2.65 year, 301 participants were newly diagnosed with CKD. The cumulative incidence rate and incidence density of CKD were 4.14%, and 16.01/1 000 person-years (95% CI: 14.20-17.82), respectively. A higher prevalence of hyperuricemia was observed in subjects with CKD compared with those without CKD. Multivariate Cox regression model analysis showed that hyperuricemia was associated with the increased risk for CKD, with an adjusted HR of 1.92 (95% CI: 1.46-2.53). Their positive associations remained in almost all the subgroups, including sex, age (<60, ≥60 years), BMI (<25.0, ≥25.0 kg/m 2), type 2 diabetes, and hypertension. A significant synergistic effect of the interaction between age and hyperuricemia on CKD was found, and the synergy index was 1.78 (95% CI: 1.18-2.68). Conclusion:The incidence of CKD in adults in Songjiang district was relatively high. Hyperuricemia is an independent risk factor for the development of CKD.

Objective: To assess the effect of coronary collateral circulation (CCC) on myocardial viabilityin patients with chronic total occlusion of left anterior descending (LAD) artery. Methods: A total of 101 consecutive patients with confirmed diagnosis of total LAD occlusion in our hospital were enrolled. Rest 99mTc-MIBISPECT myocardial perfusion and 18F-FDG PET were performed, in addition all patients received coronary angiography (CAG) at 3 months front and back. Both images were reconstructed in the same machine and QPS software was used to obtain the summed rest score (SRS), abnormal resting total perfusion defect (TPD), viable and non-viable myocardium, LVEDV, LVESV and LVEF in relevant patients. Based on CAG result, the patients were divided into 2 groups: CCC group, n=39 and No CCC group, n=62; according to existing old myocardial infarctionand location of LAD occlusion, the patients were further divided into 4 subgroups. The above parameters were compared among different groups. Results: There were 86 male and 15 female patients with the mean age at (59.92±11.43) years. Relevant parameters in CCC group and No CCC groupwere as in SRS: (21.23±9.68) vs (28.56±8.76), TPD: (30.03±13.69) %vs (40.37±12.50) %, viable myocardium: (21.77±13.12) % vs (13.66±9.23) %, non-viable myocardium (8.28±8.58) %vs (27.40±12.97) %, all P<0.05; in LVEDV: (109.82±30.01) ml vs (173.71±57.69) ml, LVESV: (62.82±22.39) ml vs (122.53±51.66) ml, LVEF: (43.85±8.46) % vs (31.03±8.30) %, all P<0.05. Conclusion: Our preliminary study found that CCC could maintain left ventricular rest perfusion, myocardial viability and protect cardiac function in patients with chronic total LAD occlusion.

Objective To investigate the changes and mechanisms of immune function after ischemic stroke by studying the reaction of C57BL/6mice's lung and spleen after ischemic stroke.Methods Sixteen mice C57BL/6 were randomly assigned to experiment group (n=8) and control group (n=8).The acute ischemic stroke model was established in experiment group by Middle Cerebral Artery Occlusion (MCAO) and no stroke was performed in control group.Then we observed the lung inflammation by HE staining of the lung.And we measured the spleen weight,spleen weight index,the count and the apoptosis index of spleen cells of mice in two groups.Results Compared with the control group,the count of the inflammatory cells in lung of mice in the experiment group was higher,the spleen weight,spleen weight index and spleen cells count of the experiment group were decreased and the apoptosis index of spleen cells of the experiment group was higher.Conclusion The mice in the experiment group have inflammatory reaction in lung,the spleen atrophied and the apoptosis index of spleen cells is increased,which suggest that stroke-induced apoptosis of immunocytes may cause immunodepression after ischemic stroke and easily lead to the infection.

Objective To explore the determination of nicotine in cigarettes by fluorescein and fluorimetry-basic possession of bonuses system.Methods Nicotine could interfere with fluorescence energy transfer between fluorimetry-basic possession of bonuses.A new way of energy transfer was established to determinate nicotine according to the fluorescence increment of fluorimetry.Results The linear range was 0.2-7.0 mg/L for the concentration of nicotine.The correlative coefficient was 0.9992.The detection limit was 0.18 mg/L.The recovery rates were 99.0 %-105 %,and RSDs were 1.1 %-4.8 % respectively.Conclusion This method is simple,fast,accurate and sensitive.It can be used to determinate nicotine in cigarettes.

This article summarizes the present researches on biology of human Demodex about the methods of examination,morphology of adult parasite,biological habits and characteristics,and in vitro survival.

AIM: To investigate the bio-effects of salusins on rat heart and cardiomyocytes. METHODS: The cardiac function was determined by multipurpose polygraph in isolated rat heart treated with various concentrations of salusin-? or salusin-?. [ 45Ca 2+] and [3H]-Leu incorporation were determined in cultured neonatal rat cardiomyocytes with ?-liquid scintillation counter. RESULTS: 10 -12-10 -7mol/L salusin-? and salusin-? had no effects on isolated rat cardiac function. However, salusin-? and salusin-? stimulated [ 45Ca 2+] uptake and [3H]-Leu incorporation. The [ 45Ca 2+] uptake induced by salusins were inhibited by nicardipine, and were synergistically increased by endothelin-1. The [3H]-Leu incorporation induced by salusin-? and salusin-? was inhibited by nicardipine, FK506 (a special inhibitor of carcineulin), PD 98059 (inhibitor of MAPK) and chelerthine (inhibitor of PKC). The effects of salusin-? on [ 45Ca 2+] uptake was stronger than those of salusin-?. But there were no statistical difference in [3H]-Leu incorporation between salusin-? and salusin-?. CONCLUSIONS: Salusin-? and salusin-? did not affect directly cardiac function in rat hearts. But salusins improved calcium uptake and protein synthesize in neonatal rat cardiomyocytes. Those effects of salusins were related with calcium channel, carcinuelin, MAPK and PKC signal pathways. Salusins may be the regulatory factors for myocardium growth and hypertrophy.