Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

Objective:To systematically integrate qualitative study on stroke patients' perception of recurrence risk, so as to providing evidence for optimizing stroke risk communication education and secondary prevention strategies.Methods:Qualitative studies related to the perception of recurrence risk in stroke patients were searched through computers on PubMed, Web of Science, Embase, CINAHL, Cochrane Library, Joanna Briggs Institute (JBI) Evidence-Based Health Care Centers Database, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Medicine Database. The search period was from the establishment of the database to September 2022. The articles quality were evaluated using the quality evaluation criteria for qualitative research of the Australian JBI Evidence-Based Health Care Center (2020) . The results were integrated by Meta-synthesis.Results:A total of 7 articles were included, 37 research results were extracted, 9 new categories were summarized, and 3 integrated results were obtained, which were respectively the perceived characteristics of recurrence risk in stroke patients, the barriers to accurate perception of recurrence risk, and the ways to actively or negatively address recurrence risk.Conclusions:In clinical practice, it is necessary to carry out early dynamic assessment of recurrence risk perception among stroke patients, attach importance to and optimize communication and education on recurrence risk, improve comprehensive support mechanisms, so as to promote stroke patients to participate in and adhere to active risk management.

Objective:To search, evaluate and summarize the best evidence on falls prevention and management in the frail elderly to provide ideas and references for clinical practice.Methods:Evidences related to falls prevention and management in the frail elderly were systematically searched on BMJ Best Practice, UpToDate, Registered Nurses' Association of Ontario, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, Medlive, Joanna Briggs Institute (JBI) Evidence Based Health Care Center Database in Australia, Scottish Intercollegiate Guideline Network, Cochrane Library, CINAHL, PubMed, Web of Science, Embase, CNKI, Wanfang Database, VIP and China Biology Medicine disc. The search period was from the establishment of the database to March 1, 2023. Three researchers independently evaluated quality of the included literature, and extracted, integrated and graded the evidence.Results:A total of 24 literatures were included, including 13 systematic reviews, 4 expert consensus, 6 guidelines and 1 evidence summary. A total of 30 evidences were summarized from 5 aspects of frailty screening, assessment, disease and medication management, exercise management and nutrition management.Conclusions:This study summarizes the best evidence for fall prevention and management in the frail elderly. It is suggested that practitioners should formulate a management plan in accordance with the actual situation in combination with the application scenario and the situation of the elderly, so as to improve the intervention level and reduce the incidence of falls in the frail elderly.

Gap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell-cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.
Cadherins ; Cell Communication ; Connexin 43 ; Osteoblasts ; Transforming Growth Factor beta1

Medical insurance payment model is transforming from project-based purchases to service bundle-based strategic purchases. The new form of bundled purchases should found on a scientifically-led design process of such bundles. The core to bundled purchase would be the payment standard, and the key to its success would be process control. Establishment of such a foundation, a core, and a key, would promote the current price standards, and lead service providers to a standardized medical service standard, so as to ensure a precise rewarding system of payment and service. The big data diagnosis-intervention packet(DIP)is able to fulfill mentioned ambitions by integrating insurance payment and supervision into one management. DIP is a full-process payment mode that encompasses pre-service estimation, in-service process control, post-service grading, and resource allocation. It is an innovative practice in line with China′s national conditions for the modern governance of medical security and medical services.

Objective:To explore the price formation method and price standard in the big data diagnosis-intervention packet.Methods:The expenditure data and income data of 95 medical institutions in Shanghai in 2018 were used for analysis, including 33 municipal hospitals and 62 district hospitals. After using the standardized data of disease score, the medical institutions in the region were divided into four quadrants with the regional average of unit price per index and cost per index as the coordinate axis. The best quadrant of income and cost was found out, namely the high quality range. The geometric center was calculated in the high quality range, and the unit price per index of the geometric center was taken as the cost standard.Results:For the district hospitals, there were 20 hospitals in the first quadrant, 8 in the second quadrant, 24 in the third quadrant and 10 in the fourth quadrant; For the municipal hospitals, there were 7 hospitals in the first quadrant, 5 in the second quadrant, 12 in the third quadrant and 9 in the fourth quadrant. In the third quadrant, the average income and cost of medical institutions were lower than the average of the city, and the income could cover the cost. The third quadrant was the high quality range. The unit price per index of the third quadrant geometric center of district hospitals was 14 115.4 yuan, and that in municipal hospitals was 15 559.1 yuan, which could be used as the corresponding cost standard.Conclusions:The price discovery mechanism based on objective data and high-quality interval geometric center method can remove the impact of unreasonable charges or unreasonable behavior on medical income, and reflect the guidance of the standard price of medical insurance payment.

One of the challenges to diagnosis-intervention packet is how to detect and avoid the institutional behavior of pursuing a higher score group. Based on the analysis method of big data, the authors analyzed the objective distribution characteristics of the treatment methods corresponding to a diagnosis, and compared the distribution of diseases with high and low scores in the region to find out the selection trend of treatment methods for the same diagnosis in various hospitals. Combined with hospital positioning, the authors found out whether there was a tendency of pursuing a higher score group. Scientific support will be provided for the reasonable payment of medical insurance expenses and the development planning of hospitals.

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by 2019 novel Coronavirus (2019-nCoV). At present, the most used method to diagnose 2019-nCoV is nucleic acid test. Suspected cases underwent real-time fluorescent RT-PCR examination, and those who were 2019-nCoV nucleic acid positive were confirmed cases. However, in the process of nucleic acid test, factors such as specimen quality, specimen transportation and storage conditions, detection reagents and methods may cause false negative or false positive results. This article reviews the factors that may affect the results of 2019-nCoV nucleic acid test, and provides a basis for the diagnosis of suspected COVID-19 cases.

Objective:To investigate the effect of Wuwei-Xiaodu Decoction in treating intra-articular calcaneal fractures after open reduction and internal fixation and its effect on hemodynamics. Methods:A total of 88 intra-articular calcaneal fractures patients admitted to Langfang People's Hospital and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from April of 2016 to February of 2019 were selected and randomly divided into the control group and the observation group (44 patients in each group) by the method of random number table. Both groups received open reduction and internal fixation for intra-articular calcaneal fractures. The control group received conventional treatment after surgery. The observation group were treated with Wuwei-Xiaodu Decoction on the basis of treatment in the control group. Both groups were treated for 12 weeks. The Gissane Angle, Bohler Angle and calcaneal height were detected by X-ray and CT. The hemodynamic analyzer was used to determine ESR, Fibrinogen (Fb), and whole blood viscosity. The recovery of foot function was evaluated by using the Ankle-posterior foot scoring system of the American Orthopaedic Association, and the fracture healing time and complications were recorded. Results:After treatment, the Gissane Angle (130.01°± 15.76° vs. 121.33°± 14.33°, t=2.793), Bohler Angle (33.04°± 5.03° vs. 28.93°± 4.31°, t=4.189) and calcaneal height (44.13 ± 6.13 mm vs. 40.06 ± 5.87 mm, t=6.556) in the observation group were significantly higher than those in the control group ( P<0.01). The fracture healing time (66.85 ± 8.17 d vs. 78.04 ± 9.44 d, t=5.945) in the observation group was significantly lower than that of the control group ( P<0.01). After treatment, serum ESR (13.65 ± 1.94 mm/h vs. 18.99 ± 2.30 mm/h, t=11.772), Fb (301.83 ± 32.04 g/L vs. 319.85 ± 33.62 g/L, t=2.536) levels and whole blood viscosity (7.04 ± 0.82 mPa?s vs. 8.34 ± 0.92 mPa?s, t=6.997) in the observation group were significantly lower than those in the control group ( P<0.01). The effective rate of foot function recovery 6 months after operation in the observation group was 97.7% (43/44) and 81.8% (36/44) in the control group, and the difference between the two groups was statistically significant ( χ2=4.456, P=0.035). The complication rate was 4.6% (2/44) in the observation group and 20.5% (9/44) in the control group, and the difference between the two groups was statistically significant ( χ2=5.091, P=0.024). Conclusions:The Wuwei-Xiaodu Decoction can promote the recovery of bone shape after open reduction and internal fixation of intra-articular calcaneal fractures, reduce the complications after operation, promote fracture healing, and improve the hemodynamics.

Once pulp necrosis or apical periodontitis occurs on immature teeth, the weak root and open root apex are challenging to clinicians. Berberine (BBR) is a potential medicine for bone disorders, therefore, we proposed to apply BBR in root canals to enhance root repair in immature teeth. An in vivo model of immature teeth with apical periodontitis was established in rats, and root canals were filled with BBR, calcium hydroxide or sterilized saline for 3 weeks. The shape of the roots was analyzed by micro-computed tomography and histological staining. In vitro, BBR was introduced into stem cells from apical papilla (SCAPs). Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity, mineralization ability, and gene expression of osteogenic makers. The signaling pathway, which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR, Western blot analysis, and immunofluorescence. In rats treated with BBR, more tissue was formed, with longer roots, thicker root walls, and smaller apex diameters. In addition, we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent manner. BBR induced the expression of β-catenin and enhanced β-catenin entering into the nucleus, to up-regulate more runt-related nuclear factor 2 downstream. BBR enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.
Animals ; Berberine ; pharmacology ; Cell Differentiation ; drug effects ; Dental Papilla ; Male ; Osteogenesis ; drug effects ; Periapical Periodontitis ; therapy ; Rats ; Stem Cells ; cytology ; drug effects ; metabolism ; Wnt Signaling Pathway ; drug effects ; Wnt3A Protein ; genetics ; metabolism ; X-Ray Microtomography