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.

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.

ObjectiveTo investigate the effect of Stemona tuberosa alkaloids （STA） on apoptosis and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase （JNK/p38 MAPK） signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups （100， 150， 200， 250， 300 mg⋅L^-1）. Thiazole blue （MTT） assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining， flow cytometry， and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2， and the expression of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， JNK， p-JNK， p38 MAPK， and p-p38 MAPK. ResultCompared with the blank group， STA groups （150， 200， 250， 300 mg⋅L^-1） demonstrated the increase in inhibition rate of cell proliferation （P<0.01） and cell clone inhibition rate， and decrease in cell clone formation rate （P<0.01）. In comparison with the blank group， STA groups showed typical characteristics of apoptosis， such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group （P<0.01）. Compared with the blank group， STA （150， 200， 250， 300 mg⋅L^-1） significantly up-regulated the protein expression of Caspase-3 and Bax （P<0.05， P<0.01） and down-regulated the expression of Bcl-2 protein （P<0.01）. Compared with the blank group， STA had no significant influence on the total protein expression of PI3K， Akt， JNK， and p38 MAPK. However， STA （150， 200， 250， 300 mg⋅L^-1） significantly decreased the levels of p-PI3K and p-Akt （P<0.05， P<0.01） and increased the level of p-p38 MAPK （P<0.05， P<0.01）. Compared with the blank group， STA （200， 250， 300 mg⋅L^-1） significantly raised the level of p-JNK （P<0.05， P<0.01）. ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.

Objective : To investigate the role of Epac1 / CaMK Ⅱ signaling pathway in myocardial ischemia reper- fusion injury (MIRI) in mice，and to investigate the protective effect of vitexin ( VT) on acute MIRI． Methods: C57 / BL mice were randomly divided into 5 groups : Sham surgery group ( Sham) ，ischemia reperfusion group ( I / R) ，and ischemia reperfusion + vitexin group ( function 3，6，12 mg / kg groups) ．Ligation of the left anterior descending coronary artery (LAD coronary artery) in mice resulted in ischemia of part of the heart tissue for 30min and reperfusion of the blood for 120min．Mouse myocardial ischemia reperfusion injury ( MIRI) model was established．In the sham operation group，only the LAD was not ligated．Serum LDH levels of mice were detected．Hema- toxylin-eosin (H＆E) staining was performed on the left ventricular myocardium of mice to observe the histopatho- logical changes．The expression level of Epac1 in myocardial tissue was observed by immunohistochemistry．The protein expressions of Epac1，Rap1，CaMK Ⅱ and ERK / p-ERK were determined by Western Blot. Results : Compared with Sham group，serum LDH level of mice in I / R group was significantly increased，protein expressions of Epac1， Rap1 and CaMK Ⅱ in myocardial tissue were significantly up-regulated，and ERK1 /2 phosphorylation level was decreased．Compared with I / R group，vitexin (3，6，12 mg / kg) pretreatment group decreased serum LDH level，inhib- ited Epac1，Rap1 and CaMK Ⅱ protein expression in mouse myocardial tissue，and promoted ERK1 /2 phosphoryla- tion(P＜0. 05 or P＜0. 01) ．The histopathological results showed that the myocardial fibers in the I / R group were disordered and broken，with increased gaps and obvious inflammatory cell infiltration．In the vitexin treatment group，the myocardial fibers were arranged more neatly and inflammatory cells were infiltrated less. Conclusion Vitexin may regulate Epac1 / CaMK Ⅱ signaling pathway，down-regulate CaMK Ⅱ protein expression，increase ERK phosphorylation，and effectively reduce MIRI.

ObjectiveTo investigate the material basis and mechanism of Arnebia euchroma against hepatocarcinoma by network pharmacology， and to verify the potential targets of A. euchroma against hepatocarcinoma by molecular docking and experiments. MethodThe main active ingredients of A. euchroma were collected by retrieving the literature through China National Knowledge Network （CNKI） and Traditional Chinese Medicine System Pharmacology Database and Analysis Platform（TCMSP）. The active ingredients were screened out by FAFDrug4 platform according to the pharmacokinetics （ADME） properties of the drugs. The screening compounds and liver cancer targets were collected by using several databases and analyzed by drawing Venn diagrams. The protein-protein interaction （PPI） network was constructed by Cytoscape and STRING database. DAVID database was used to perform Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of key targets. Autodock was used to perform molecular docking of targets on core pathways. Cell counting kit-8 （CCK-8） experiment was carried out to validate the activities of five naphthoquinones. Based on the predicted results in the H22 tumor-bearing mouse model， the key targets of isovalerylshikonin against hepatocarcinoma were verified by hematoxylin-eosin （HE） staining， enzyme-linked immunosorbent assay （ELISA）， and Western blot assay. ResultFifty-five active ingredients and 34 targets of active ingredients against hepatocarcinoma were screened out. The active molecules with high degree values in the “drug-active ingredient-target-disease” network were mainly naphthoquinones. PPI network obtained several core targets of A. euchroma against hepatocarcinoma. Twenty-two pathways were screened out by KEGG analysis， mainly involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， vascular endothelial growth factor （VEGF）， tumor necrosis factor （TNF）， and other signaling pathways. The results of molecular docking showed that the five naphthoquinones had a good affinity with the targets of the PI3K/Akt signaling pathway. The results of CCK-8 and animal experiments showed that the lipid-soluble component isovalerylshikonin had good anti-cancer potential， and the high-dose group reduced the serum levels of VEGF and alpha fetoprotein （AFP） levels and elevated interferon-γ （IFN-γ） level （P<0.05， P<0.01）. The high-dose group also down-regulated phosphorylate（p）-Akt （Ser473） and B-cell lymphoma （Bcl）-2 protein expressions and up-regulated Bcl-2-antagonist of cell death （Bad） protein expression （P<0.01）. ConclusionA. euchroma can inhibit hepatocarcinoma cell proliferation and tumor angiogenesis and induce cancer cell apoptosis through the PI3K/Akt signaling pathway， which provides ideas and clues for the subsequent in-depth investigation of its specific mechanism.

Piperine is a kind of amide alkaloids presenting in Piper nigrum L.，which has the pharmacological action such as protecting cardiovascular system ，regulating glucose and lipid metabolism ，anti-tumor，improving nervous system diseases ， anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ，as the main active ingredient of P. nigrum ，could protect the cardiovascular system by reducing inflammation and oxidative stress ；improve mitochondrial function through anti-inflammatory and antioxidant effects ，thereby regulate glucose and lipid metabolism ；play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin，NF-κB/Nrf-2/KeAP-1/HO-1， PI3K/Akt，TGF-β1/Smad2/ERK1/2；improve neurological diseases by inhibiting autophagy ，relieving inflammation ，improving antioxidant，inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ；play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However，the mechanism of action of piperine is not perfect ，and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ，without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ，the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.

ObjectiveTo study the effect of apigenin on the proliferation and apoptosis of human colon cancer CL187 cells and the underlying mechanisms. MethodHuman colorectal cancer CL187 cells were treated with different concentrations of apigenin （0， 30， 45， 60 mg·L^-1） according to the results of the preliminary experiment. The proliferation of CL187 cells was detected by methyl thiazolyl tetrazolium （MTT） and colony formation assays， and the apoptosis was observed via Hoechst 33258 staining. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of cysteine protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the CL187 cells treated with apigenin. Western blot was employed to measure the protein levels of Caspase-3， Bcl-2， and Bax associated with apoptosis， protein kinase B （Akt） and phosphorylated Akt （p-Akt） in phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway， and extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （MAPK）， and p-p38 MAPK protein in MAPK pathway. ResultCompared with the blank group， the apigenin groups had low cell survival rates and high inhibition rates on cell proliferation （P<0.01）. Apigenin decreased the cell clone number and clone formation rate， and increased the inhibition rate on clone formation （P<0.01）. After CL187 cells were treated with different concentrations of apigenin for 48 h， typical apoptosis characteristics such as nuclear pyknosis， chromatin condensation， and enhanced fluorescence reaction were observed. Compared with blank group， 45， 60 mg·L^-1 apigenin treatments down-regulated the mRNA level of anti-apoptotic gene Bcl-2 （P<0.01） and all the apigenin treatments up-regulated those of the pro-apoptotic genes Bax and Caspase-3 （P<0.05， P<0.01）. Similarly， apigenin treatments down-regulated the protein level of Bcl-2 （P<0.05， P<0.01） and up-regulated those of Caspase-3 （P<0.05， P<0.01） and Bax （P<0.01， 45， 60 mg·L^-1）. The blank group had higher protein level of Akt than the 60 mg·L^-1 apigenin group （P<0.01）， higher protein levels of p-Akt， ERK1/2， and p-ERK1/2 than the 45， 60 mg·L^-1 apigenin groups （P<0.01）， and higher protein levels of JNK and p-JNK than the apigenin groups （P<0.05， P<0.01）. Compared with blank group， 60 mg·L^-1 apigenin up-regulated the protein level of p38 MAPK （P<0.05）， and all the apigenin groups up-regulated that of p-p38 MAPK （P<0.01）. Furthermore， apigenin lowered the p-Akt/Akt ratio （P<0.05， P<0.01） and p-ERK1/2/ERK1/2 ratio （P<0.01）， while it increased the p-JNK/JNK ratio （45， 60 mg·L^-1； P<0.05， P<0.01） and p-p38 MAPK/p38 MAPK ratio （P<0.05， P<0.01）. ConclusionApigenin can inhibit the proliferation and promote the apoptosis of CL187 cells by inhibiting the PI3K/Akt signaling pathway and regulating the expression of proteins in the MAPK signaling pathway.

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.

Objective:To explore the effect of comprehensive follow-up mode in patients with chronic obstructive pulmonary disease (COPD) .Methods:From February to June 2019, a total of 80 COPD patients in The First Affiliated Hospital of Guangxi Medical University were enrolled and divided into the control group and the comprehensive follow-up group (40 cases in each group) . All patients were given home rehabilitation program guidance and health education. The control group was followed up using telephone, while the comprehensive follow-up group were followed up by telephone combined with Internet which lasted for one year. The differences of pulmonary function, motor function, compliance and recurrence between the two groups were compared.Results:One year after discharge, percentage of forced vital capacity to the predicted value (FVC%) , percentage of forced expiratory volume in one second to the predicted value (FEV1%) , 6 minutes walking distance, SF-36 quality of life and rehabilitation compliance rate in the comprehensive follow-up group were higher than those of the control group, while CAT score, mMRC score, number of patients with acute attack of COPD and recurrence rate were lower than those of the the control group, and the differences were statistically significant ( P<0.05) . Conclusions:For CPOD patients, the comprehensive follow-up mode can effectively reduce the 1-year recurrence rate, promote the recovery of respiratory and motor functions, and improve compliance and quality of life.

The disease treatment of patients with gastrointestinal cancer is accompanied by impaired bodily functions. Frailty is very common in patients with gastrointestinal cancer, and is closely related to its various adverse health outcomes, which seriously affects their prognosis. This article reviews the risk factors, correlation with adverse health outcomes and intervention methods of frailty in gastrointestinal cancer patients. It is pointed out that medical and nursing staff should identify the frailty state of patients with gastrointestinal cancer as soon as possible and make early interventions to improve the prognosis of patients.