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.

Male primary adenocarcinoma of urethra is rare clinically. A patient with primary adenocarcinoma of posterior urethra complicated with intestinal metaplasia was admitted and underwent urethral mass resection. The tumor recurred 3 months after surgery and no further treatment was given for personal reasons. The purpose of this report is to improve clinicians' understanding of urethral cancer, so that patients can undergo more accurate diagnosis and treatment.

Humans ; COVID-19 ; Quarantine ; Renal Dialysis ; SARS-CoV-2 ; Hospitals

Objective To compare the clinical efficacy of posterior pedicle screw fixation through Wiltse paraspinal approach and posterior traditional open approach in the treatment of thoracolumbar fracture and dislocation.Methods A retrospective case control study was performed based on the clinical data of 40 patients with thoracolumbar fracture and dislocation admitted between January 2013 and January 2016.All the surgeries were performed through posterior midline incision,and they were divided into two groups according to different approaches.Patients in Group A received pedicle screw fixation through Wiltse paraspinal approach while Group B received fixed pedicle screw through open surgery.Group A was composed of 12 males and 8 females,aged 21-60 years [(41.5 ±9.6)years].Group B was composed of 13 males and 7 females,aged 18-58 years [(39.1 ± 13.1) years].The same surgical procedures were adopted in spinal decompression,reduction,and the spinal vertebral interbody bone graft and fusion surgery in the two groups.Operation duration,intraoperative blood loss,postoperative drainage volume,visual analogue scale (VAS),spinal canal patency at the last follow-up,percentage of postoperative injury of vertebral height recovery,and Cobb angle were compared.CT and MRI were used to evaluate postoperative paravertebral muscle atrophy,and American spinal injury association (ASIA) impairment scale was used to evaluate neurological function assessment.Results All patients were followed up for 9-33 months,with (19.3 ± 5.6) months for Group A and (22.5 ± 4.9) months for Group B (P ＞ 0.05).The operation duration was (240.5 ± 38.3) min in Group A and (258.5 ± 43.7) min in Group B (P ＞ 0.05).The intraoperative blood loss was (525.0 ± 168.2) ml in Group A,less than (770.0 ± 269.2) ml in Group B (P ＜ 0.05).Postoperative drainage volume was (190.1 ± 78.9) ml in Group A,less than (281.7 ± 122.3) ml in Group B (P ＜ 0.05).VAS score 24 hours after operation and at the last follow-up in Group A was (6.4 ± 1.0) points and (1.6 ± 0.5) points,respectively,better than those in Group B [(7.8 ± 0.7) points and (2.2 ± 0.4) points] (P ＜ 0.05).No significant differences were observed in terms of spinal canal patency at the last follow-up,percentage of postoperative injury of vertebral height recovery,and Cobb angle [Group A:(85.3 ± 3.7) ％,(85.5 ± 2.7) ％,and (4.7 ± 1.2)°;GroupB:(85.8±1.8)％,(88.8 ±1.3)％,and (5.3 ±1.5)°] (P＞0.05).In terms of MRI evaluation score of postoperative paravertebral muscle atrophy,Group A reported better results than Group B [(2.1 ± 0.6) points vs.(1.2 ± 0.6) points] (P ＜ 0.05).At the last follow-up,there were 7,5,6,1 and 1 patients in Group A,while 6,6,5,2 and 1 patients in Group B at ASIA grades A,B,C,D and E (P ＞ 0.05).Within the same group,significant difference was observed between the preoperative data and that at the last follow-up in terms of postoperative VAS score,spinal canal patency,percentage of injury of vertebral height,Cobb angle,and ASIA impairment scale (P ＜ 0.05).Conclusion For thoracolumbar fracture and dislocation,compared with traditional open approach,posterior pedicle screw fixation through Wiltse paraspinal approach can effectively restore the vertebral body height and spinal canal patency and can reduce the intraoperative bleeding,postoperative drainage,postoperative back pain,and paravertebral lesion.

OBJECTIVE: To establish a rapid method for EBV detection with loop-mediated isothermal amplification (LAMP), and to make it as a clue for early diagnosis of nasopharyngeal carcinoma cancer. METHOD: EBV DNA was fast extracted from samples after boiling, while the whole detection will be finished within an hour with specific amplification of EBV gene by LAMP. RESULT: High specificity was shown from EBV detection of 33 clinical samples. Comparing with PCR, LAMP is more simple and convenient to perform under isothermal conditions, and require no special apparatus, thus, it is more economical and practical. CONCLUSION LAMP analysis of EBV may be an efficient and easy way for clinical diagnosis of nasopharyngeal carcinoma.
DNA Primers ; DNA, Viral ; analysis ; Herpesvirus 4, Human ; genetics ; Humans ; Molecular Sequence Data ; Nasopharyngeal Neoplasms ; diagnosis ; Nucleic Acid Amplification Techniques ; Sensitivity and Specificity