OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

Pan-vascular medicine is an emerging discipline focusing on atherosclerotic diseases,with the concept of multidisciplinary integration,emphasizing on exploring the mechanism of disease development from the whole of the organism's structure and function.At present,the basic mechanism system of pan-vascular diseases has yet to be perfected.The pan-vascular concept is highly compatible with the idea of Chinese medicine that focuses on the overall view.Deficiency of all qi is the root cause of pan-vascular diseases,while phlegm,blood stasis,and water-dampness and other tangible evils stagnate in the veins and channels as the symptoms of the disease,therefore,the disease mechanism can be highly summarized as"stagnation due to qi deficiency".Deficiency leads to the stagnation,blocking the veins and channels,and the deficiency worsens due to the stagnation and then damages the veins and channels,thus,it develops into a disease.Based on the theory of"stagnation due to qi deficiency",this paper takes endothelial cell dysfunction as the entry point of pan-vascular diseases,and considers that low endothelial cell immunity is the initiating factor of pan-vascular diseases,and that the widespread persistence of microinflammatory state is the key pathology to pan-vascular diseases.

Shared decision-making is a medical model developed in the 1970s where physicians and patients jointly participate in making healthcare decisions. It has been widely adopted in developed countries in Europe and the United States. In recent years, more and more studies have explored the localization of shared decision-making in China, but the clinical application model in Chinese context has not yet been established. This article reviews the basic concept, clinical application, advantages and disadvantages, and future development of the shared decision-making between doctor and patient, in hope of providing ideas for the construction of a shared decision-making model in China.

Objective This study aims to investigate possible hub genes,associated pathways,and transcription fac-tors between chronic periodontitis(CP)and Parkinson's disease(PD).Methods Gene expression profiles of CP(GSE16134,GSE23586,and GSE10334)and PD(GSE20141 and GSE49036)were downloaded from the gene expres-sion omnibus(GEO)database for differential expression analysis and functional clustering analysis.The protein-protein interaction(PPI)network was constructed,and hub genes were screened by four topological analysis algorithms and modular segmentation.Functional clustering analysis was performed.The hub genes were validated by external datasets of CP and PD,and causal relation was further assessed by Mendelian randomization(MR).Results After merging the data,1 211 differentially expressed genes(DEGs)were screened in the CP datasets;of which,551 were upregulated and 660 were downregulated.A total of 2 407 DEGs were screened in the PD dataset,of which,1 438 were upregulated and 969 were downregulated.The PPI network included 145 nodes and 126 edges.Four hub genes(FCGR3B,PRF1,IL18,and CD33)and three transcription factors(HSF1,HSF2,and HSF4)were finally screened.The relevant pathway was pre-dominantly natural killer(NK)cell-mediated toxic effects.The MR results suggest a possible positive causal relationship between CP and the risk of developing PD.Conclusion This study indicated the probably shared pathophysiology and possible causal relationship between CP and PD and may offer novel concepts and therapeutic targets for future mecha-nistic investigations.

OBJECTIVES: To investigate possible cross-talk genes, associated pathways, and transcription factors between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD). METHODS: The gene expression profiles of CP (GSE10334 and GSE16134) and COPD (GSE76925) were downloaded from the GEO database. Differential expression and functional clustering analyses were performed. The protein‑protein interaction (PPI) network was constructed. The core cross-talk genes were filtered using four topological analysis algorithms and modular segmentation. Then, functional clustering analysis was performed again. RESULTS: GSE10334 detected 164 differentially expressed genes (DEGs) (119 upregulated and 45 downregulated). GSE16134 identified 208 DEGs (154 upregulated and 54 downregulated). GSE76925 identified 1 408 DEGs (557 upregulated and 851 downregulated). The PPI network included 21 nodes and 20 edges. The final screening included seven cross-talk genes: CD79A, FCRLA, CD19, IRF4, CD27, SELL, and CXCL13. Relevant pathways included primary immunodeficiency, the B-cell receptor signaling pathway, and cytokine-cytokine receptor interaction. CONCLUSIONS This study indicates the probability of shared pathophysiology between CP and COPD, and their cross-talk genes, associated pathways, and transcription factors may offer novel concepts for future mechanistic investigations.
Humans ; Chronic Periodontitis/genetics* ; Gene Regulatory Networks ; Gene Expression Profiling ; Protein Interaction Maps/genetics* ; Pulmonary Disease, Chronic Obstructive/genetics*

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

Objective:To explore the status quo and influencing factors of self-management behavior of patients with diabetic retinopathy (DR) based on the ABC-X model.Methods:Totally 315 DR patients who were hospitalized in the Department of Ophthalmology of Henan Provincial People's Hospital from May to September 2022 were selected by convenience sampling and investigated with the general information questionnaire, Summary of Diabetes Self-Care Activities (SDSCA), Diabetes Distress Scale (DDS) and Social Support Rating Scale (SSRS). A total of 315 questionnaires were distributed, and 305 valid questionnaires were recovered, with an effective recovery rate of 96.8%.Results:The SDSCA, DDS and SSRS scores of 305 DR patients were (39.59±9.49), (37.44±10.53) and (37.42±3.65), respectively; self-management behavior was positively correlated with the number of hospitalizations and social support ( P<0.01), negatively correlated with psychological distress ( P<0.01). The results of multiple linear regression analysis showed that the type of residence, course of disease, number of hospitalizations, psychological distress of diabetes and social support were the influencing factors of self-management behavior of DR patients ( P<0.05) . Conclusions:The level of self-management behavior of DR patients is yet to be improved. Medical and nursing staff should provide targeted interventions to improve their quality of life and prognosis.

Objective:To investigate the knowledge, attitude and practice status of ophthalmic nurses on prevention and control of intraocular infection in grade Ⅲ class A hospitals.Methods:A self-made questionnaire was used to investigate the knowledge, attitude and practice of 236 nurses on prevention and control of intraocular infection in the ophthalmology department of 8 grade Ⅲ class A hospitals in Zhengzhou from January to June 2020. The correlation between the knowledge, attitude and practice were analyzed by Pearson correlation analysis and the influencing factors of each term were analyzed by multivariate Logistic regression.Results:The scores of knowledge, attitude, practice of all nurses were (26.08 ± 2.46), (67.45 ± 8.48), (50.31 ± 6.67) points, and the scoring rate were (87.0 ± 8.2)%, (84.3 ± 10.1)%, (83.9 ± 9.8)%, respectively. The scores of each dimension of knowledge, attitude and practice were significantly positively correlated ( r values were 0.26-0.42, all P<0.05), respectively. Multivariate Logistic regression analysis showed that education background, professional title and training experience of infection were the influencing factors of knowledge score ( P<0.05), education background, professional title, training experience of infection and demand were the influencing factors of attitude score ( P<0.05), and nursing age and work post were the influencing factors of practice score ( P<0.05). Conclusions:The level of knowledge, attitude and practice of ophthalmic nurses in grade Ⅲ class A hospitals on prevention and control of intraocular infection is overall good. Hospital management department still needs to make reasonable management countermeasures according to personnel characteristics to improve the knowledge, attitude and practice level of ophthalmic nurses and to reduce post-operative intraocular infection.