Objective To investigate whether aberrant DNA methylation of ubiquinol-cytochrome C reductase core protein 1(UQCRC1)is related to cognitive impairment caused by neonatal sevoflurane exposure.Methods A total of 94 SPF C57 mice of either sex,aged 6 d,and weighing 4～6 g,were randomly divided into 7 groups:control group(Con,n=6),sevoflurane-6 and-24 h exposure groups(Sev-6 and-24 h,n=6),control+DMSO group(Con+DMSO,n=19),control+5-aza-2'-deoxycytidine(5-AZA,methylation inhibitor)group(Con+5-AZA,n=19),sevoflurane+DMSO group(Sev+DMSO group,n=19),and sevoflurane+5-AZA group(Sev+5-AZA group,n=19).From 6 to 8 d after birth,the mice of the Sev-6 and-24 h exposure groups were exposed to 3％sevoflurane daily(with 97％oxygen,2 L/min,2 h per day),while those from the Con groups were given exposure of 100％oxygen(2 L/min,2 h per day).For the mice of the 5-AZA and DMSO groups,1 mg/kg of 5-AZA or an equal volume of DMSO was injected intraperitoneally 30 min before daily exposure.In 6 and 24 h after the last exposure to sevoflurane,6 mice from the Con,Sev-6 h,and Sev-24 h groups were euthanized for biochemical analysis,and in 24 h post-exposure,6 mice from the Con+DMSO,Con+5-AZA,Sev+DMSO,and Sev+5-AZA groups were randomly selected for biochemical analysis,while another 3 mice from above each group were also randomly selected for morphological analysis.The remaining 10 mice in these groups underwent behavioral testing(open field test,novel object test,and Y-maze test)at 30～33 d after birth to assess cognitive function,and were euthanized in 24 h after the final behavioral test.RT-qPCR and Western blotting were used to detect the hippocampal expression of UQCRC1,DNA methyltransferases(Dnmts),and methyl CpG binding protein 2(Mecp2)at mRNA and protein levels,respectively.Immunofluorescence assay was employed to observe the distribution and expression of UQCRC1 in the hippocampus.Bisulfite sequencing PCR(BSP)was applied to measure the methylation in the UQCRC1 promoter region.Results Compared with the Con group,the mRNA and protein levels of UQCRC1 were down-regulated(P<0.05),and the mRNA level of Dnmts was up-regulated(P<0.05)in both the Sev-6 h and Sev-24 h exposure groups,while the methylation level in the UQCRC1 promoter region was enhanced in the Sev-24 h exposure group(P<0.05).Additionally,the Sev+5-AZA group had obviously increased mRNA and protein levels of UQCRC1(P<0.05),and notable improvement in cognitive impairment(P<0.05)when compared with the Sev+DMSO group.Conclusion Hypermethylation of UQCRC1 promoter region and thus down-regulating its mRNA and protein expression might be the main mechanism by which repeated neonatal sevoflurane exposure induces cognitive impairment later in life.

ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

Objective To detect the expression of p-ERK5 and WT-1 in cancer tissues of the patients with high-grade serous ovarian cancer(HSOC),and to analyze their relationship with the prognosis of the pa-tients to provide a basis for judging the prognosis of HSOC patients.Methods Fifty-four patients with HSOC visiting in the gynecology and obstetrics department of the Affiliated Hospital of North China University of Technology from January 2008 to December 2019 were selected as the study subjects.The age,clinical stage,lymph node metastasis,complicating ascites,recurrence within 3 years,platinum sensitive,interval debulking surgery(IDS)and CA125 level at first visit were collected.The ovarian cancer tissue samples were collected.The expression levels of p-ERK5 and WT-1 protein in ovarian cancer tissues were detected by immunohisto-chemistry.The expression situation of the two kinds of factors were compared among different clinicopatho-logical features.The Kaplan-Meier method and COX regression analysis were used to evaluate the prognosis of the patients with HSOC.Results The median progress free survival(PFS)in the p-ERK5 and WT-1 protein low-expression groups was 36.0 months and 37.0 months respectively,which in the high-expression groups was 17.0 months and 15.0 months respectively.The median overall survival(OS)in the p-ERK5 and WT-1 protein low expression group was 90.0 months,which in the high expression group was 40.0 months,and the difference was statistically significant(P＜0.001).Conclusion The high expression of p-ERK5 and WT-1 protein is associated with PFS time and OS time.

Objective To investigate the current status of frailty in patients on maintenance hemodialysis(MHD),and explore the correlation of frailty with anxiety and depression.Methods General information,clinical data and blood biochemical data of 101 cases who underwent MHD in Department of Nephrology,Shunde Hospital Affiliated to Jinan University from January 2023 to January 2024 were collected.FRAIL scale was applied to evaluate the frailty of the patients,and they were accordingly classified into frailty group and non-frailty group(including pre-frail and non-frail participants).Anxiety and depression were evaluated by GAD-7 and PHQ-9 scale.Univariate analysis and logistic regression were used to explore the association of frailty with anxiety,depression and other possible influencing factors.Results Among the 101 cases,29 cases(28.71%)were includedin frailty group and 72 cases(71.29%)in non-frailty group.There were 42 patients with depression(41.58%)and 25 with anxiety(24.75%).In the frailty group,the prevalence of depression was 65.52%and that of anxiety 55.17%.There were significant differences in age,grip strength,exercise,stroke and coronary heart disease,anxiety and depression,ferritin and CRP between the two groups(P＜0.01).Multivariate regression analysis showed that depression,anxi-ety,no exercise,stroke and high ferritin concentration were independent risk factors for frailty in MHD patients(P＜0.05).Conclusion In patients on MHD,frailty is closely associated with depression,anxiety,and lack of exercise,and stroke as well as high ferritin concentration are independent risk factors for frailty.

OBJECTIVE To explore the intracellular expression changes of p38 and Erk1/2 under three phototoxic conditions, compare three detection methods, and further investigate their molecular mechanisms. METHODS The methods involved using three testing approaches to assess the phototoxicity of chlorpromazine(CPZ) and tiaprofenic acid(TA). Subsequently, whole-cell lysates from the biological samples used in the three testing methods were collected, and the changes in the expression levels of intracellular p38 and Erk1/2 were evaluated using Western blotting. RESULTS All three testing methods accurately identified CPZ and TA as phototoxic compounds. In the 3T3 NRU phototoxicity assay, compared to the control group, the expression of p38 significantly increased under phototoxic doses of TA and CPZ(P<0.05), a phenomenon not observed in other testing methods. In phototoxicity assays using guinea pig and artificial skin models, similar expression pattern changes were observed for p38 and Erk1/2. CONCLUSION p38 and Erk1/2 have obvious dose dependence and high sensitivity in the 3T3 NRU phototoxicity test, and can be considered as potential molecular markers for evaluating the phototoxicity of 3T3 NRU. However, they have not been feasible in guinea pig tests and EpiKutis artificial skin tests. Guinea pigs and EpiKutis artificial skin exhibit more similar changes in p38 and Erk1/2 expression, suggesting that the EpiKutis artificial skin model test method may be a better alternative to animal testing than the 3T3 NRU method.

Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative IL-34 gene expression in BALF for 28-day mortality in patients with severe pneumonia, as well as the predictive power of serum IL-34 for severe pneumonia. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare cumulative survival rates. Cox regression analysis was conducted to explore risk factors for 28-day mortality in patients with severe pneumonia. Pearson correlation analysis was used to assess the correlation between serum IL-34 levels and relative IL-34 gene expression in BALF of patients with severe pneumonia. Results Serum IL-34 levels were higher in the severe pneumonia group than those in the non-severe pneumonia group, and were higher in the non-severe pneumonia group than in the control group (P < 0.05). Serum IL-34 levels and relative IL-34 gene expression in BALF were higher in the non-survival group than in the survival group (P < 0.05). ROC curve analysis showed that the areas under the curve for predicting 28-day mortality in patients with severe pneumonia were 0.908 for serum IL-34 levels and 0.878 for relative IL-34 gene expression in BALF. The optimal cutoff value for serum IL-34 levels in predicting severe pneumonia was 129.9 pg/mL. Multivariate Cox regression analysis showed that increased serum IL-34 levels and increased relative IL-34 gene expression in BALF were independent risk factors for 28-day mortality in patients with severe pneumonia (P < 0.05). The Kaplan-Meier survival analysis results indicate that, with a cutoff value of 129.9 pg/mL, patients with severe pneumonia who had high serum levels of IL-34 exhibited a lower cumulative survival rate compared to those with low IL-34 level(Log-rank P < 0.001). Conclusion Serum IL-34 levels are significantly increased in patients with severe pneumonia, and relative IL-34 gene expression in BALF is positively correlated with serum IL-34 levels. Both can be used as indicators for predicting the prognosis of 28-day mortality in patients with severe pneumonia.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Objective:To analyze the expression and significance of circ-BCAR3 in gastric cancer tissues, and to explore the effect and molecular mechanism of silencing circ-BCAR3 on the proliferation and invasion of gastric cancer cells. Methods:The expression of circ-BCAR3 in gastric cancer tissues and adjacent normal tissues was analyzed using the UCSC database. The relationship between circ-BCAR3 expression and the survival rate of gastric cancer patients was analyzed by Kaplan-Meier method. Small interfering RNA (siRNA)-negative control (si-NC) and si-circ-BCAR3 were transfected into gastric cancer BGC823 cells, and recorded as si-circ-BCAR3 group and si-NC group, respectively. Real-time reverse transcription-PCR (RT-qPCR) was used to detect the expression of circ-BCAR3 gene in gastric cancer NCI-N87, AGS, BGC823, HS-746T, SGC7901 cells, and immortalized gastric mucosal epithelial GES-1 cells. The proliferation and invasion abilities of BGC823 cells were detected by clone formation assay and Transwell assay, respectively. The binding sites of circ-BCAR3 and miR-145-5p were predicted using the online Circinteractome platform, and their targeting relationship was verified by a dual luciferase reporter gene assay. The relationship between the expression of circ-BCAR3 and miR-145-5p in gastric cancer tissues was analyzed using the UCSC database. The expression levels of vascular endothelial growth factor receptor-2 (VEGFR-2) signaling pathway proteins, including phosphorylated VEGFR-2 (p-VEGFR-2), phosphorylated phospholipase C-λ (p-PLC-λ), phosphorylated extracellular signal-regulated kinase (p-Erk), and phosphorylated P38 (p-P38), were detected in BGC823 cells using Western blotting analysis. Results:The relative expression level of circ-BCAR3 in gastric cancer tissues (8.04±2.34) was significantly higher than that in adjacent normal tissues (2.53±1.74), and the difference was statistically significant ( P<0.01). The survival rate of gastric cancer patients with low circ-BCAR3 expression was higher than that of gastric cancer patients with high circ-BCAR3 expression, and the difference was statistically significant ( P<0.05). The relative expression levels of circ-BCAR3 in NCI-N87, HS-746T, AGS, BGC823, and SGC7901 cells (5.05±0.36, 3.50±0.21, 2.87±0.38, 6.80±0.29, and 3.77±0.53) were all higher than those in GES-1 cells (1.02±0.21), and the differences were statistically significant (all P<0.01). The number of clones formed in the si-NC group and si-circ-BCAR3 group were [(126.70±21.78) and (44.89±8.33) unit], respectively, and the number of invasive cells were [(53.81±5.92) and (24.91±4.56) unit], respectively, with statistically significant differences ( P<0.01). The AACUGGA sequence in circ-BCAR3 was found to have the capacity to bind to the UUGACCU sequence in miR-145-5p. The luciferase activity of wild type circ-BCAR3 (WT- circ-BCAR3)+ miR-145-5p group (0.26±0.03) was lower than that of WT- circ-BCAR3+miR-NC group (1.00±0.05), and the difference was statistically significant ( P<0.01). In contrast, for the miR-NC, the luciferase activities of the mutant- circ-BCAR3 (MUT- circ-BCAR3)+ miR-145-5p and MUT- circ-BCAR3+ miR-NC groups were (1.07±0.12) and (1.00±0.09), and the differences were not statistically significant ( P>0.05). The expression of circ-BCAR3 and miR-145-5p showed a negative correlation in gastric cancer tissues ( R=0.82, P<0.01). The relative expression levels of VEGFR-2 signaling pathway proteins p-VEGFR-2, p-PLC-λ, p-Erk, and p-P38 in BGC823 cells in the si-circ-BCAR3 group (1.08±0.21, 1.50±0.21, 3.01±0.25, and 0.46±0.10) were lower than those in the si-NC group (5.22±0.17, 5.56±0.19, 6.63±0.31, and 4.24±0.16), and the differences were statistically significant (all P<0.05). Conclusions:The expression of circ-BCAR3 is elevated in gastric cancer tissues and cells. Furthermore, silencing of circ-BCAR3 may inhibit the proliferation and invasion of BGC823 cells by regulating the miR-145-5p/VEGFR-2 signaling pathway.

In recent years, the application of complex interventions in fields such as public health, clinical research, and education has become a trend. Due to the complexity of interventions, target populations, or implementation contexts, complex intervention research can help clarify the mechanism of interventions, determine factors such as contexts related to outcome changes, and evaluate the feasibility and scalability of intervention plans. Based on the update of the complex intervention guidelines and research examples, this article summarizes the complex interventions' characteristics and core elements of the update, combs the development of the complex interventions research framework, and explains the specific content of the research phase, with a view to providing reference for the rational development of complex intervention research in the domestic nursing field.

Purpose: Anxiety, depression, and poor quality of life (QOL) were considered important concerns that hindered the rehabilitation of breast cancer survivors. A number of studies have investigated the effects of physical activity, but they have not reached the same conclusions. This review aimed to identify the effects of physical activity on QOL, anxiety, and depression in breast cancer survivors. Methods: PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, SinoMed, CNKI, Vip, and WanFang databases were searched for the time period between January 1, 2012, and April 30, 2022. Studies were included if they were randomized controlled trials of the effects of physical activity on QOL, anxiety, or depression in breast cancer survivors. The tools of the Joanna Briggs Institute were used to assess the quality of the included studies. R software version 4.3.1 was used for meta-analysis. Results: A total of 26 studies, involving 2105 participants, were included in the systematic review. Among these, 20 studies involving 1228 participants were included in the meta-analysis. Compared with the control group, the results indicated that physical activity can significantly improve QOL(Hedges' g = 0.67; 95% CI 0.41–0.92) and reduce anxiety (Hedges' g = −0.28; 95% CI −0.46 to −0.10) in breast cancer survivors. However, the effect of physical activity on depression (Hedges' g = −0.46; 95% CI −0.99 to 0.06) was not statistically significant. Conclusions Physical activity was an effective intervention to improve QOL and reduce anxiety in breast cancer survivors, as well as showed positive trends in depression, although without statistical significance. More well-designed studies are required to clarify the effects of different types of physical activities on the QOL, anxiety, and depression among breast cancer survivors.