ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage （固本防哮饮） for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group， model group， low-， medium-， and high-dose of Guben Fangxiao Beverage group and montelukast sodium group， with 6 mice in each group. Except for the normal group， ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding， the low-， medium-， and high-dose groups of Guben Fangxiao Beverage were respectively given 12， 24， and 36 g/（kg·d）， the montelukast sodium group was given montelukast sodium granule 2.6 mg/（kg·d）， and the mice in the normal group and model group were given 20 ml of double-distilled water， all by gavage， once a day for 28 days. The levels of interleukin 4 （IL-4） and interleukin 5 （IL-5） in the lung tissue of mice were detected； HE staining was used to observe the pathology of the lung tissue and to score the inflammation； DHE staining was used to observe the level of reactive oxygen species （ROS） in the lung tissue， and the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ in the lung tissue were detected； the levels of serum superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA） and adenosine triphosphate （ATP） were detected； the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， haem oxygenase 1 （HO-1） and cAMP responsive element binding protein （CREB） in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group， the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score； DHE staining showed an increase in the level of ROS， and an increase in the levels of IL-4 and IL-5 in the lung tissues； the levels of serum SOD， CAT， and ATP were reduced， and the level of MDA was elevated； the activities of the mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ of the lung tissues were reduced， and the activities of p-AMPK， Nrf2， CREB protein expression decreased （P＜0.05）. Compared with the model group， the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced； the levels of ROS， IL-4 and IL-5 in the lung tissue were reduced； the levels of CAT and ATP in the serum increased， and the content of MDA was reduced； and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ， as well as the expression of CREB protein， were elevated in the lung tissue （P＜0.05）. Compared with the high-dose group， the MDA level of the medium-dose Guben Fangxiao Beverage group decreased （P＜0.05）. The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group， and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group （P＜0.05）. ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission， and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.

The expression level of NOD-like receptors(NLRP3)inflammasome is significantly elevated in breast cancer tissues,and a high level of NLRP3 inflammasomes is closely associated with breast cancer metastasis.Activation of NLRP3 inflammasome can induce the release of inflammatory factors into the tumor microenvironment(TME).These inflammatory factors,by signaling to cancer cells,reshape the TME to promote tumor growth and invasion,ultimately facilitating the process of epithelial-mesenchymal transition.This equips cancer cells with the ability to establish distant metastases and increase the formation of metastatic lesions.This review addresses the current research status and prospects of NLRP3 inflammasomes in the breast cancer TME and their role in breast cancer metastasis.The goal is to provide new insights for the study of breast cancer metastasis mechanisms and treatment strategies.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

The essence of cirrhosis is the over-repairing reaction of liver tissue damage in the process of chronic liver disease.During repair,the liver parenchyma is gradually replaced by fibrosis tissue,resulting in changes in liver tissue morphology,followed by portal hypertension and other related manifestations.Liver failure are serious disorder of liver functions(synthesis,metabolism,transformation,regeneration,etc.)caused by various factors,often mainly manifested as jaundice,coagulation disfunction,hepatic encephalopathy,ascites,etc.The naming and typing of the two are different,and they can exist independently of each other or intersect with each other.In recent years,with the in-depth exploration of cirrhosis and liver failure,many new definitions and classification methods have been put forward in the research.However,due to the confusion of classification methods,there is still a lack of summary,so this article briefly reviews the current progress of clinical classification of liver cirrhosis and liver failure and their differences and intersections.

Objective To explore the cognitive load level and influencing factors of emergency nurses.Methods Using convenience sampling method,48 nurses in emergency department of China-Japan Friendship Hospital from April to May 2022 were selected as research objects.General data were collected and total cognitive load and three different types of cognitive load were measured.Results Regression analysis showed that nurse-patient relationship was influencing factor of total cognitive load of nurses in emergency department(β=6.202,P=0.007),the noisy working environment was the influencing factor of the internal cognitive load(β=1.042,P<0.001),and the living situation(sharing with others)was the influencing factor of the external cognitive load(β=-3.917,P=0.006).The factors of associated with cognitive load were not found.Conclusion The total cognitive load and the three types of cognitive load of nurses in emergency department are high.Nursing managers can reduce the cognitive load of nurses in emergency department by adjusting related influencing factors,so as to improve nursing work efficiency.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Objective To investigate the protective effect and mechanism of propofol on the blood-brain barrier in rats with cerebral ischemia.Methods A total of 48 10-week-old male SD rats were randomly divided into the sham group,the cerebral ischemia group,the propofol group and the propofol+LY294002 group.Twenty-four hours before the induction of the model,the rats in the propofol+LY294002 group were intracerebroventricularly injected with PI3K inhibitor LY294002(0.3 mg·kg-1),and the rats in the other groups were administrated with saline(10 μL).Rats in the cerebral ischemia group,the propofol group and the propofol+LY294002 group established cerebral ischemia models by carotid artery occlusion.Rats in the sham group only isolated the common carotid artery and ligated the external carotid artery without other treatment.During the modeling period,the rats in the propofol group and the propofol+LY294002 group were given propofol(10 mg·kg-1)via the tail vein,and the sham group and the propofol group were treated with saline.After 24 hours,the neurological function of rats was evaluated by Zea Longa method;the area of cerebral infarction was detected by TTC staining;the degree of cerebral edema was detected by the dry-wet weight method.EB tracer method was used to evaluate the integrity of the blood-brain barrier;ELISA was used to detect inflammatory cytokines in cerebrospinal fluid;Western blot was used to detect the expression of PI3K/AKT signaling pathway proteins and blood-brain barrier tight junction proteins Claudin-5 and Occludin.Results Cerebral ischemia led to the increase of neurological function scores and local infarction of brain tissues in rats.Compared with the sham group,the EB content in the brain tissue of rats in the cerebral ischemia group increased,the degree of brain edema increased,and the content of inflammatory cytokines in the cerebrospinal fluid increased.And the use of propofol could significantly decrease the neurological function scores,reduce the area of cerebral infarction,inhibit EB penetrating blood-brain barrier,reduce the degree of brain edema,reduce the release of inflammatory cytokines,and up-regulate the expression of PI3K/AKT signaling pathway proteins and tight junction proteins Claudin-5 and Occludin.LY294002 significantly reversed the above effects of propofol.Conclusion Propofol can maintain the expression of tight junction proteins Claudin-5 and Occludin through the PI3K/AKT signaling pathway,protect the structural and functional integrity of blood-brain barrier,reduce the degree of brain edema,prevent other inflammatory cytokines into the brain tissue,reduce cerebral infarction,and alleviate the neurological functional damage caused by cerebral ischemia.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.