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 comprehensively evaluate the clinical value of Elecsys serum abnormal prothrombin (PIVKA-Ⅱ) test reagent for auxiliary diagnosis of hepatocellular carcinoma (HCC) in the Chinese population.Methods:A multicenter case-control design was used in the study. Samples from patients with first-time confirmed, diagnosed, and untreated HCC, benign liver disease and interfering controls were collected continuously. Elecsys PIVKA-II and alpha-fetoprotein (AFP) were tested for analysis. Various clinical details of the subjects were collected and analyzed. The efficacy of PIVKA-II (21.29 ng/ml) and AFP (400 ng/ml) for HCC diagnosis was calculated at specific positive cut-off values. Statistical analysis was performed using the Kruskal-Wallis test or receiver operating characteristic curve.Results:A total of 448 subjects were eventually enrolled from five centers, including 185 HCC cases. PIVKA-II had a higher diagnostic sensitivity and accuracy than AFP (84.86% vs. 30.81% and 89.01% vs. 63.66%) when the benign liver disease group was used as the control group, while the specificity was slightly lower. A sensitive analysis showed that PIVKA-II had a sensitivity of >80% at this specific positive cut-off value in the subgroup of AFP-negative subjects, patients with different etiologies, and HCC patients with multiple Barcelona Clinic liver cancer stages (including early-stage HCC). At the same time, the PIVKA-II subject had a slightly higher area under the receiver operating characteristic curve than the AFP (0.920 0 vs. 0.880 9).Conclusion:The clinical efficacy of Elecsys PIVKA-Ⅱ is good and stable in the Chinese population. Additionally, it has the clinical potential to improve the current missed diagnosis status of AFP-negative HCC and HCC monitoring at an early stage, as well as the effectiveness of accuracy promotion for HCC auxiliary diagnosis in China.

Abstract In recent years, mental health issues have gradually expanded from adults and professional groups to the primary and secondary school students, and are showing a trend of younger age. The article analyzes the "Special Action Plan for Comprehensively Strengthening and Improving the Mental Health Work of Students in the New Era (2023-2025)" jointly issued by 17 departments including the Ministry of Education. It explores the current situation, overall concept, key tasks, and other aspects to further improve the "four in one" student mental health work system of health education, monitoring and warning, consulting services, intervention disposal, and improve students mental health literacy.

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

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 method which could measure tongue muscle thickness and evaluate the fasciculation of the tongue muscle by submental way ultrasonic detection , and to obtain the reference values of tongue muscle thickness in healthy volunteers , exploring its clinical application in the patients with amyotrophic lateral sclerosis (ALS).Methods In two-hundred healthy volunteers who took physical examination at the Medical Examination Center of Peking University Third Hospital , the tongue thickness was determined by measuring the distance between the upper and lower surfaces of the lingual muscles in the center of the plane perpendicular to the Frankfurt horizontal plane of the frontal section with a 3.5 MHz convex array transducer .The fasciculation of tongue muscle was evaluated using a 7.5 MHz linear array transducer in the same position .This method was used to measure the thickness of tongue muscle and to evaluate tongue muscle fasciculation in 30 patients with ALS who visited neurological clinic with the diagnosis of possible or definite ALS according to revised El Escorial criteria during the same period .We compared the tongue muscle thickness between 30 ALS patients and the same number of age-and gender-matched healthy volunteers .Results The mean value of tongue muscle thickness of males was significantly higher than that of females ((4.09 ±0.52) cm vs (3.70 ±0.56) cm, t=5.108, P<0.01), but there was no significant difference in the tongue muscle thickness between the different age groups .The mean value of tongue muscle thickness was significantly correlated with the body mass index value in healthy subjects ( r=0.412, P<0.01).No tongue muscle fibrillation was detected in healthy volunteers .In ALS group, the tongue was significantly thinner than that in healthy subjects ((3.77 ±0.58) cm vs (4.05 ±0.49) cm, t=-0.253, P<0.05).Of the total 30 ALS patients, we recognized tongue muscle fasciculation in 12 (40%).Conclusion The method to measure tongue muscle thickness and evaluate tongue musclefibrillation is reliable , and has good clinical application value in related diseases such as ALS .

Objective To observe the characteristics of midbrain hyperechogenicity of amyotrophic lateral sclerosis (ALS) patients by transcranial sonography (TCS).Methods A total of 107 ALS patients,enrolled from January to July 2015 in Beijing University Third Hospital,with the diagnosis of possible or definite ALS according to revised E1 Escorial criteria were examined by transcrinal B-mode sonography.The area of midbrain and substantia nigra and the area ratio of hyper-substantia nigra/midbrain (S/M) were measured and compared between ALS and 40 age-and gender-matched controls.Results There were 29.0％ (31/107) of ALS patients and 7.5％ (3/40) of controls who displayed abnormal midbrain hyperechogenic areas for groups comparison (x2 =22.708,P ＜ 0.01).The hyperechogenic substantia nigra area and S/M were (0.40 ± 0.14) cm2 and 9.5％ (6.0％,13.0％) in ALS group,whereas (0.20 ± 0.06) cm2 and 5.0％ (2％,6.0％) in control group respectively,the difference between the two groups being statistically significant (t =12.727,Z =16.545,both P ＜0.01).No correlations of hyperechogenic area sizes in ALS patients were found in regard to age,gender,ALS duration or ALS Functional Rating Scale score (r=0.043,-0.088,0.018,0.202;P=0.251,0.512,0.894,0.190).However,there was significant correlation between TCS severity and ALS subtype (bulbar vs spinal form,r =0.386,P ＜ 0.01).Conclusion Hyperechogenicity of the substantia nigra was found in patients with sporadic ALS with a frequency higher than in controls.

Objective To investigate the pathogenesis of cerebral infarction after non-cardiac surgeries according to imaging.Methods Retrospective analyses of clinical and imaging data of 17 patients with postoperative cerebral infarction(average 68 years old,total incidence 0.049％)from departments of orthopedics and general surgery were conducted during 52 months.Results Cerebral infarction occurred 39.1 hours after operation on average.Among the 17 patients,eight were detected with disturbance of consciousness,ten with hemiplegia,six with speech disorder and two with unilateral sensory disturbance.Six (35.3％)had blood lipids tests.Five(29.4％)had neck vascular ultrasound and one had intracranial magnetic resonance angiography(MRA).When discharged,one patient was declared death and ten had impaired neurological function in various degrees.Among six patients with previous stroke,one(16.7％)received neurological consultation before surgery.According to the image manifestation,ten cases were territory circulation infarcts,four centrum ovale infarcts and three watershed infarcts.Conclusions This study suggests that total incidence of cerebral infarction after non-cardiac surgeries is lower than previously reported and there is greater involvement of atherosclerosis.Patients' conditions should be closely observed within at least four days after surgeries.Preoperative assessment should be strengthened in order to avoid occurrence of postoperative cerebral infarction.

Based on the CT data, a medical treatment FE model of hip joint prosthesis with stepped stem was rebuilt according the anatomy of the hip joint. Under the loads of 1.5 times standard body weight (70kg), the mechanical behavior of the treatment model was calculated, and the influence of step structure and distribution for stepped stem on femur stress and stability of total hip replacement were analyzed by three-dimensional finite element analysis (3D-FEA). The results show that the step structure changs the bone stress transmission on the interface of stepped stem and femur, and benefits to reduce stress-shielding in the femur. For the same distribution of step, the reduction of stress-shielding for raised stepped stem is better than that for concave stepped stem. The raised stepped stem of which the steps is distributed one of third part of the stem is of the best effect of reduction of stress shielding in all of the analysis models, and is a beneficial mechanical design to relieves osteoporosis or osteopenia of femur caused by stress-shielding and improve the reliability of it in clinic.
Adult ; Arthroplasty, Replacement, Hip ; methods ; Biomechanical Phenomena ; Computer Simulation ; Equipment Failure Analysis ; Finite Element Analysis ; Hip Prosthesis ; Humans ; Imaging, Three-Dimensional ; Male ; Models, Biological ; Prosthesis Design ; Stress, Mechanical ; Tomography, Spiral Computed ; Weight-Bearing ; physiology

Quite a few orthopedics experts have fabricated some novel bone scaffolds with nanotechnology and have carried out some researches on nano-biological effects. The study of the biological effects about nano-biomaterials can facilitate the understanding of the interaction between the biomaterials and the organism, and provide research ideas and direction to construct new biomaterials with physiological function. To better understand the interaction of nano biomaterials with protein, cells and bio-security, this review presents recent advances of biological effects about nano scaffold for bone tissue engineering.
Biocompatible Materials ; metabolism ; Bone Substitutes ; Bone and Bones ; Humans ; Nanostructures ; Nanotechnology ; Surface Properties ; Tissue Engineering ; methods ; Tissue Scaffolds