Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

ObjectiveTo improve the response capabilities to disasters and prevent major epidemics， it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises， to enhance the overall quality of the teams. MethodsFirst， a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification （IEC） standards of the national emergency medical rescue team. Then， based on the outcome based education （OBE） concept， we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally， an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023， as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators， the five core competencies in the evaluation system， including rescue skills， medical and health knowledge， disaster coping ability， team cooperation ability， and mental resilience training， were positively correlated with the cumulative number of trainings （r=0.71， r=0.76， r=0.81， r=0.84， r=0.96，all P<0.05）， indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.

As a type of experiential psychotherapy,Satir communication model can help the individual system and the family system achieve a state from dysfunction to healthy function,which can enrich the intervention connotation of family support and provide a new direction for the realization of full-life circle care.This paper aims to introduce the concept,core elements,common treatment techniques,application and effects,current challenges and relevant suggestions of Satir communication model in the nursing field from the perspective of family support,in order to provide references for the localization development and clinical integration of Satir communication model in the field of nursing in China.

Objective To investigate the intervention effect and mechanism of sinomenine(SIN)on Parkinson's disease(PD)mice based on GSK3 β/Nrf2/HO-1 and NF-κ B signaling pathways.Methods C57BL/6 mice were randomly divided into 6 groups:normal group,model group,positive drug group(Levodopa,75 mg?kg-1)and SIN low-,medium-and high-dose groups(20,40,80 mg?kg-1),with 8 mice in each group.Mice were intraperitoneally injected with 20 mg?kg-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once a day for 5 days.Intragastric administration was performed 1 hour after injection of MPTP,once a day for 12 days.On the day 11 of administration,the mice were subjected to a pole-climbing experiment,and on the day 12,a rotating rod experiment was performed to test the behavioral changes of the mice.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in brain tissue were detected by RT-qPCR.The protein expression levels of TH,Nrf2,HO-1,p-GSK3β,GSK3β,p-IκB,IκB,p-NF-κB and NF-κB in brain tissue were detected by Western Blot.Results Compared with the normal group,the automatic turning latency(T-turn)of the model group was significantly prolonged(P＜0.05),and the number of falls was significantly increased(P＜0.001).The expression level of TH protein in brain tissue was significantly decreased(P＜0.01),and the mRNA expression levels of IL-1β,TNF-α and IL-6 were significantly increased(P＜0.001).The serum levels of TNF-α,IL-1β and IL-6 were significantly increased(P＜0.05,P＜0.01).The protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly decreased(P＜0.05,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly increased(P＜0.001).Compared with the model group,the T-turn in the Sin medium-and high-dose groups was significantly shortened(P＜0.05,P＜0.001),the falling latency was significantly prolonged(P＜0.05,P＜0.01),the times of falls was significantly reduced(P＜0.001),the expression level of TH protein in brain tissue was significantly increased(P＜0.01,P＜0.001),and the level of serum TNF-α was significantly decreased(P＜0.05).The mRNA expression levels of IL-1β,TNF-α and IL-6 in brain tissue of mice in each administration group were significantly decreased(P＜0.001),the serum levels of IL-1β and IL-6 were significantly decreased(P＜0.01,P＜0.001),the protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly decreased(P＜0.001).Conclusion SIN can enhance anti-oxidative stress and inhibit neuroinflammation by regulating GSK3β/Nrf2/HO-1 and NF-κB pathways in the brain of Parkinson's disease mice,thereby exerting neuroprotective effects.

【Objective】 To investigate the correlation between perioperative zero red blood cell(RBC) transfusion and the prognosis of patients with acute Stanford type A aortic dissection. 【Methods】 A retrospective analysis was made on 96 patients who underwent one-stop Hybrid surgery for acute Stanford type A aortic dissection in our hospital from May 2021 to May 2022. The patients were divided into two groups according to whether they received perioperative RBC transfusion: zero RBC transfusion group (group A, n=26) and RBC transfusion group (group B, n=70). The preoperative general data and laboratory indexes were recorded and the propensity score matching method was used to screen the patients with the same preoperative baseline data, with comparison of operation-related indicators, intraoperative and postoperative blood component dosage and prognostic indicators. 【Results】 With BMI index, hemoglobin, platelet count, and troponin T as co variables, 48 patients were included in the study after matching according to 1∶1 propensity score: Group A (n=24) and Group B (n=24). Compared with group A, hemoglobin and hematocrit in group B decreased significantly at the end of operation and 24 h after operation, with a statistically significant difference (P<0.05). There was no significant difference between the two groups in operation-related indicators, intraoperative and postoperative blood component dosage, in-hospital mortality, continuous renal replacement therapy, incidence of infection and cerebral infarction (P>0.05). 【Conclusion】 The perioperative hemoglobin of patients with acute Stanford type A aortic dissection with zero RBC transfusion did not significantly decrease, and the postoperative complications and mortality did not increase.

Lateral canals are small branches from the main root canal, usually extending from the dentin and cementum into the periodontal ligament, mostly located at the lower 1/3 of the apical portion. Due to the complex and varied anatomical morphology as well as the high incidence, it becomes an important factor affecting the effect of root canal therapy and a difficult point in this process. It is of great clinical significance to master the treatment strategy of lateral canals during root canal therapy. This article reviews the anatomical characteristics of lateral canals, as well as the clinical identification, treatment strategy and the laboratory detection methods of lateral canals in the process of root canal preparation, disinfection, and obturation.

Objective:To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI).Methods:① In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). ② In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 μmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. Results:① The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. ② The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2 -ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT) : 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2 -ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2 -ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1β mRNA (2 -ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2 -ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2 -ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. Conclusions:Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Family physicians contracted service is an important choice to deepen the reform of China′s healthcare reform and achieve the strategic goal of " health for all" . In order to effectively promote the contracted service, the central government has successively issued a number of policy documents, which are echoed by the localities in their proactive explorations, achieving remarkable results. But there are also multiple roadblocks hindering the contracted service to progress. This article referred to the three-circle theory and studied policy implementation from the three dimensions of policy value, policy resources, and policy impetus. A thorough analysis of the problems in the implementation process revealed such main problems as insufficient family physicians, inadequacy of supporting policies and low level of policy acceptance among the young healthy age groups. The follow-up work will promote the long-term implementation of the family physicians contracted service policy by enriching the family physicians team, enriching supporting policies, and focusing on promotions to key age groups.

Objective: To investigate the usage of medical and health care APP among female college students, and to understand possible influencing factors, so as to provide reference for medical health care behaviors and personal health among college students. Methods: A stratified random sampling method was used to select 891 female college students from 3 colleges in Weifang. A questionnaire survey on their concentration on their own health, the knowledge, cognition and behavior of medical and health care APP, and Logistic regression analysis was used to analyze the influencing factors. Results: There were 55.4% female college students who had used medical and health care APP, and most of them (290) had used fitness and weight loss APP. There was statistical significance of the different usages of students of different degrees, majors and grades(χ2=26.55, 7.72, 13.96, P<0.05). Logistic regression analysis showed that educational background, annual medical costs, awareness of medical and health care APP and attitude towards APP prospect were the factors influencing the utilization of medical and health care APP (OR=0.44，0.69，1.36，1.23，P<0.05). Conclusion The usage rate of medical and health care APP is general, and sustained utilization rate is low, the APP should enrich menstrual period consumption and figure report, add video recommendation, interactive dating, and other functions, improve female students medical and health care APP cognition, female college students to change health care APP attitude.

Objective To investigate the protective role of Sestrin2 overexpression in hypoxia and re-oxygenation injury (H/R) injury of hippocampal neurons and its mechanism in rats.Methods Neurons were enzymatically isolated from hippocampi of newborn Sprague-Dawley rats (less than 24 h old) and culturedinvitro. These neurons were randomly assigned into 4 groups (n=20) using a random number table: control group, H/R group, vector group and Sestrin2 overexpression group. The hippocampal neurons were seeded in 6-well plates at a density of 2×104 cells/mL; neurons in the latter two groups were transfected with lentiviruses containing empty vector andSestrin2overexpressed genes, respectively; the hippocampal neurons in the later three groups were subjected to oxygen-glucose deprivation (OGD) for 6 h followed by restoration of O2 supply for 20 h. The reactive oxygen species (ROS) content was detected by Reactive Species Assay Kit, and the ATP concentration was detected by ATP Assay Kit. Cell apoptosis rates were measured by flow cytometry. The levels of Sestrin2, dynamin-related protein 1 (Drp1), Fis1, and apoptosis-related proteins Bcl-2, Bax and cytochrome C (Cyt C) were measured by Western blotting. The ratio of Bcl-2 to Bax was calculated. The ultrastructure of mitochondria was observed by transmission electron microscopy.Results As compared with control group, H/R group had significantly lower ATP concentration, Bcl-2 protein expression and ratio of Bcl-2 to Bax ([11.15±0.42] nmol/mg proteinvs. [5.30±0.39] nmol/mg protein; 2.20±0.26vs. 0.91±0.02; 6.46± 0.41vs. 1.04±0.05), statistically higher average fluorescence intensity of ROS and cell apoptosis rate (152.41±17.38vs. 1530.00±14.69; 3.77％±0.74％vs. 56.57％±1.35％), and significantly higher protein levels of Sestrin2, Drp1, Fis1, Bax and Cyt C (0.66±0.06vs. 1.11±0.20; 0.48±0.03vs. 1.16±0.07; 1.14± 0.09vs. 2.47±0.09; 0.34±0.03vs. 0.88±0.04; 0.17±0.03vs. 0.30±0.03,P<0.05); what's more, the structure of mitochondria was obviously destroyed in I/R group. As compared with H/R group, Sestrin2 overexpression group had significantly increased ATP concentration, Sestrin2 and Bcl-2 protein expressions and ratio of Bcl-2 to Bax ([8.95±0.27] nmol/mg protein; 2.67±0.07; 1.80±0.19; 3.95±0.28), significantly lower average fluorescence intensity of ROS and cell apoptosis rate (337.27±15.32; 10.33％±2.60％), and statistically lower protein levels of Drp1, Fis1, Bax and Cyt C (0.43±0.02; 1.11±0.08; 0.45± 0.02; 0.17±0.02,P<0.05); the structure of mitochondria was relatively completed in Sestrin2 overexpression group.Conclusion Sestrin2 overexpression can inhibit mitochondrial fission, reduce accumulation of reactive oxygen species, improve mitochondrial energy metabolism and block mitochondria mediated apoptosis pathway, thereby alleviating I/R injury of rat hippocampal neurons.