Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.

Objective:To investigate the impact of receptor-interacting protein kinase 3 (RIPK3) on major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI), as well as the predictive performance of RIPK3 combined with traditional cardiovascular risk factors.Methods:This study was a single-center prospective cohort study. It included patients with AMI who underwent PCI at Peking Union Medical College Hospital between September 2017 and November 2017. Baseline clinical data were collected, and plasma samples were obtained 6 hours after PCI to measure RIPK3 levels. Follow-up was conducted via outpatient visits or phone calls to record the occurrence of MACE, including cardiovascular death, hospitalization for heart failure, and vascular events (recurrent AMI or stroke). The predictive performance of RIPK3, traditional cardiovascular risk factors and their combination for MACE was compared using receiver operating characteristic (ROC) curves. Patients were divided into low- and high-RIPK3 level groups based on the optimal cutoff value of RIPK3. Multivariate Cox proportional hazards regression analysis was used to assess the impact of RIPK3 levels on MACE after PCI in AMI patients. Kaplan-Meier survival curves were plotted, and the log-rank test was used to compare MACE incidence between the low-and high-RIPK3 groups.Results:A total of 103 AMI patients who underwent PCI were included, aged 63.0 (56.0, 69.0) years, and 83 (80.6%) were male. The follow-up time was 5.17 (2.81, 5.17) years, during which 44 patients (42.7%) experienced MACE. The ROC curve analysis showed that the area under the curve ( AUC) for traditional cardiovascular risk factors was 0.68 (95% CI: 0.58-0.78), while the AUC for plasma RIPK3 was 0.72 (95% CI: 0.62-0.82). The combined AUC for traditional risk factors and RIPK3 was 0.75 (95% CI: 0.65-0.85). Multivariate Cox proportional hazards regression analysis indicated that plasma RIPK3 level is greater than or equal to the optimal cutoff value of 440.9 μg/L ( HR=3.31, 95% CI: 1.53-8.30, P=0.005) was an independent risk factor for MACE in AMI patients after PCI. Kaplan-Meier survival analysis demonstrated that the high-RIPK3 group had a significantly higher risk of MACE after PCI compared to the low-RIPK3 group (log-rank P=0.006). Conclusions:Elevated plasma RIPK3 level is an independent risk factor for MACE in AMI patients after PCI. Plasma RIPK3 combined with traditional cardiovascular risk factors can more effectively predict the occurrence of MACE in AMI patients after PCI. AMI patients with RIPK3≥440.9 μg/L have a higher risk of MACE after PCI.

Knee osteoarthritis(OA)is a primary cause of joint dysfunction.Knee osteotomy has garnered significant attention due to its potential to delay the progression of knee OA and enhance joint function.As a pivotal biomechanical factor in the onset and progression of OA,the accurate correction of abnormal knee alignment is the central objective of knee osteotomy.This article systematically reviews the biomechanical research progress related to knee osteotomy,with a focus on the precision and personalized correction of force line.The development of new classification system and measurement technology of force line is summarized,the biomechanical mechanism of knee OA induced by abnormal mechanical load is analyzed,and the goal of force line and clinical application progress of knee osteotomy is discusses,so as to provide a new perspective and idea for the clinical treatment of knee OA with knee osteotomy.

Knee osteoarthritis(OA)is a primary cause of joint dysfunction.Knee osteotomy has garnered significant attention due to its potential to delay the progression of knee OA and enhance joint function.As a pivotal biomechanical factor in the onset and progression of OA,the accurate correction of abnormal knee alignment is the central objective of knee osteotomy.This article systematically reviews the biomechanical research progress related to knee osteotomy,with a focus on the precision and personalized correction of force line.The development of new classification system and measurement technology of force line is summarized,the biomechanical mechanism of knee OA induced by abnormal mechanical load is analyzed,and the goal of force line and clinical application progress of knee osteotomy is discusses,so as to provide a new perspective and idea for the clinical treatment of knee OA with knee osteotomy.

Objective:To investigate the impact of receptor-interacting protein kinase 3 (RIPK3) on major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI), as well as the predictive performance of RIPK3 combined with traditional cardiovascular risk factors.Methods:This study was a single-center prospective cohort study. It included patients with AMI who underwent PCI at Peking Union Medical College Hospital between September 2017 and November 2017. Baseline clinical data were collected, and plasma samples were obtained 6 hours after PCI to measure RIPK3 levels. Follow-up was conducted via outpatient visits or phone calls to record the occurrence of MACE, including cardiovascular death, hospitalization for heart failure, and vascular events (recurrent AMI or stroke). The predictive performance of RIPK3, traditional cardiovascular risk factors and their combination for MACE was compared using receiver operating characteristic (ROC) curves. Patients were divided into low- and high-RIPK3 level groups based on the optimal cutoff value of RIPK3. Multivariate Cox proportional hazards regression analysis was used to assess the impact of RIPK3 levels on MACE after PCI in AMI patients. Kaplan-Meier survival curves were plotted, and the log-rank test was used to compare MACE incidence between the low-and high-RIPK3 groups.Results:A total of 103 AMI patients who underwent PCI were included, aged 63.0 (56.0, 69.0) years, and 83 (80.6%) were male. The follow-up time was 5.17 (2.81, 5.17) years, during which 44 patients (42.7%) experienced MACE. The ROC curve analysis showed that the area under the curve ( AUC) for traditional cardiovascular risk factors was 0.68 (95% CI: 0.58-0.78), while the AUC for plasma RIPK3 was 0.72 (95% CI: 0.62-0.82). The combined AUC for traditional risk factors and RIPK3 was 0.75 (95% CI: 0.65-0.85). Multivariate Cox proportional hazards regression analysis indicated that plasma RIPK3 level is greater than or equal to the optimal cutoff value of 440.9 μg/L ( HR=3.31, 95% CI: 1.53-8.30, P=0.005) was an independent risk factor for MACE in AMI patients after PCI. Kaplan-Meier survival analysis demonstrated that the high-RIPK3 group had a significantly higher risk of MACE after PCI compared to the low-RIPK3 group (log-rank P=0.006). Conclusions:Elevated plasma RIPK3 level is an independent risk factor for MACE in AMI patients after PCI. Plasma RIPK3 combined with traditional cardiovascular risk factors can more effectively predict the occurrence of MACE in AMI patients after PCI. AMI patients with RIPK3≥440.9 μg/L have a higher risk of MACE after PCI.

The dynamic changes of cognitive function has been paid more and more attention by foreign scholars.Dynamic assessment based on ecological momentary assessment(EMA)can capture subtle changes in cognitive function and provide more comprehensive information for early identification and timely intervention of people with cognitive impairment, which is an effective supplement to traditional cognitive assessment.This paper reviewed the concept of ecological momentary assessment, its advantages in cognitive assessment, its feasibility and effectiveness, and its application status in the evaluation of cognitive function in the elderly, so as to provide a reference for making ecological assessment of the cognitive function for older adults that is in line with China's national conditions.

Objective:To explore the mediating role of self-perceptions of aging between frailty and cognitive function in community-dwelling older adults.Methods:From February to July 2021, a total of 528 elderly people in Xinxiang community were investigated with the frailty phenotype, the brief self-perceptions ageing questionnaire and the Mini-mental state examination(MMSE) scale.According to the MMSE total score and education level, the subjects were divided into cognitive impairment group (illiteracy≤17, primary school≤20, junior high school and above≤24, n=74) and cognitive normal group( n=454). SPSS 25.0 software was used for common method deviation test, descriptive statistics and correlation analysis, while AMOS 24.0 software was used to build structural equation model and Bootstrap method was used for intermediary effect test. Results:(1)The prevalence of cognitive impairment among the elderly in the community was 14.1%. The differences between the cognitively normal group and cognitively impaired group were statistically significant in terms of age, education, number of chronic diseases suffered and depression ( χ2=59.21, 6.53, 9.84, 25.47, all P<0.05). The differences were statistically significant in terms of frailty( χ2=75.65, P<0.001) and self-perceptions of aging ( t=77.67, P<0.001). (2)Self-perceptions of aging in the cognitively impaired group (47.39±8.66) was higher than that in the cognitively normal group (38.22±8.24) ( t=77.67, P<0.001) .Frailty score in cognitively impaired group (2.00 (1.00, 3.00)) was higher than that in the cognitively normal group (0.00 (0.00, 1.00))( Z=-8.63, P<0.001) . (3)Frailty was negatively correlated with cognitive function ( r=-0.492, P<0.01), and positively correlated with self-perceptions of aging ( r=0.540, P<0.01). Self-perceptions of aging was negatively correlated with cognitive function ( r=-0.541, P<0.01) . After controlling the influencing factors such as age, education level, chronic diseases and depression, the correlation was still significant (all P<0.01) . (4) Self-perceptions of aging played a partially mediating role in the relationship between frailty and cognitive function, the mediating effect accounted for 58.5% of the total effect. Conclusion:Frailty and self-perceptions of aging have a significant impact on the cognitive function of the elderly in the community, and self-perceptions of aging plays a partial intermediary role between the frailty and cognitive function of the elderly in the community.

Multi-Efficacy of One Drug (MEOD) refers to the traditional Chinese medicines (TCM) with diverse efficacies.MEOD,one of the important characteristics of TCM,is regarded as the basis of clinical rational drug use.However,there have been few reports on the MEOD research so far.In this paper,with rhubarb selected as a typical model drug,metabolomics and network pharmacology analysis are integrated to investigate the mechanisms of MEOD with the employment of the two animal models of constipation and jaundice.Then,the biological target network of MEOD is established for promoting the precision of the quality control and clinical use of TCM.

OBJECTIVETo explore the expression of NF-E1b in colorectal cancer tissues and its association with various clinicopathological parameters and prognosis of the patients.

METHODSClinicopathological and follow-up data of 168 colorectal cancer patients undergoing radical operation at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from 2005 to 2012 were retrospectively analyzed, including 96 males and 72 females, with mean age of (57.8±11.2) years. The expression of NF-E1b protein was detected in samples of 168 resected colorectal cancer tissues and 45 adjacent non-cancerous tissues by immunohistochemistry. The expression rates of NF-E1b were compared among different clinicopathological features. Moreover, the association between NF-E1b expression and prognosis was analyzed.

RESULTSThe expression of NF-E1b protein located mainly in cytoplasm. Positive rate of NF-E1b expression in adjacent non-cancerous tissues was 17.8% (8/45), which was obviously lower than 67.9%(114/168) of cancer tissues with significant difference (χ(2)=36.376, P=0.000). Clinicopathological parameters analysis suggested that the expression level of NF-E1b in cancer tissues was associated with age (χ(2)=4.862, P=0.030), TNM staging (χ(2)=10.969, P=0.002), lymph node metastasis (χ(2)=7.390, P=0.008) and distal metastasis (χ(2)=17.887, P=0.000). The median follow-up time was 23(1-77) months. The overall 5-year survival of this cohort was 33.3%. Colorectal cancer patients with high levels of NF-E1b expression showed a worse overall survival compared with those with low levels of NF-E1b expression (18.4% vs. 56.6%, P=0.000). Univariate Cox regression analysis showed that tumor location (P=0.034), tumor size (P=0.003), TNM staging (P=0.000), depth of tumor invasion (P=0.009), lymph node metastasis (P=0.000), distant metastasis (P=0.000) and NF-E1b expression level (P=0.001) were associated with the prognosis of colorectal cancer patients. Multivariate Cox regression analysis revealed that tumor diameter >4 cm (HR=2.193,95% CI:1.334 to 3.603, P=0.002), distant metastasis (HR=2.064, 95% CI:1.160 to 3.672, P=0.014) and high NF-E1b expression (HR=1.994,95% CI:1.068 to 3.724, P=0.030) were independent risk factors of predicting poor prognosis of colorectal cancer patients.

CONCLUSIONSNF-E1b expression up-regulates in colorectal cancer tissues. High expression of NF-E1b is associated with poor prognosis of colorectal cancer patients. NF-E1b may serve as a potential target of the treatment for colorectal cancer.

Aged ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Digestive System Surgical Procedures ; Female ; GATA2 Transcription Factor ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Up-Regulation

Object To set up the quantitative method for determining the puerarin in Gegen Qinlian Decoction (GQD) by RP-HPLC and to study the change of puerarin contents in various combinations of GQD. Methods L 8(2 7) orthogonal design and statistic analysis (SPSS 10.0) were used, the puerarin contents in the samples were determined by HPLC. Results Influence of Radix Scutellaria, Rhizoma Coptidis and Radix Glycyrrhizae Preparata on the puerarin content in GQD was insignificant. And interactions between two of three were insignificant too. In this experiment, puperarin in the sedimentation was found in the compatible decoction of Rhizoma Coptidis and Radix Puerariae. Conclusion The puerarin content is not markedly influenced by Radix Scutellaria, Rhizoma Coptidis and Radix Glycyrrhizae Preparata. Maybe, the change of pH is relevant to the sedimentation in the compatible decoction contained Rhizoma Coptidis. and Radix Puerariae