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 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 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 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.

ObjectiveTo compare and observe the effect of Reduning injection （mainly clearing heat）， Shenfu injection （mainly warming Yang） combined with gefitinib on the proliferation， apoptosis， stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer （NSCLC） cell lines were selected and intervened with gefitinib （5， 10， 20 μmol·L^-1）， Reduning injection （0.6%， 0.9%）， Shenfu injection （0.6%， 0.9%）， gefitinib combined with Reduning injection， and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 （CCK-8） assay， and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 （Sox2） and aldehyde dehydrogenase family 1 member A1 （ALDH1A1） were determind by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging （FLI） and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group， Reduning injection reduced the survival rate of lung cancer cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， and up-regulated the redox ratio of cells （P<0.05）， while Shenfu injection exerted no remarkable effect on the above indexes. In addition， compared with gefitinib alone， Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells （P<0.05）， promoted the cell apoptosis （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， up-regulated the redox ratio of cells （P<0.05）， and lowered the proton efflux rate of glycolysis （P<0.05）， while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells， while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） should be used in combination with heat-clearing Chinese medicines.

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.

Objective:To investigate the risk factors of infection with polymyxin resistant and carbapenemase-resistant Klebsiella pneumoniae（PR-CRKP）. Methods:A total of 170 patients with CRKP infection admitted in the Third Affiliated Hospital of Soochow University from July 2020 to October 2023 were enrolled，including 123 cases of CRKP infection and 47 cases of PR-CRKP infection. The general conditions，exposure of antibacterial drugs 6 months before admission，laboratory test indicators at admission，antibacterial drug use when target bacteria were detected，length of hospital stay and time of invasive procedures in two groups were retrospectively analyzed. The risk factors of PR-CRKP infection were analyzed with univariate and multivariate logistic regression. SPSS 26.0 software was used to analyze the data.Results:Univariate analysis showed that compared with the CRKP group，the average age of patients in PR-CRKP group was older（ Z = -2.186， P = 0.029），the proportion of patients with exposure history to semisynthetic penicillins，carbapenems，polymyxins，and quinolones 6 months before admission was higher（ χ 2= 3.930，5.414，11.939，8.478，all P < 0.05），the proportion of infections diagnosed at admission and blood urea nitrogen levels（ χ 2= 7.268， Z = -2.406， P = 0.007 and 0.016）was higher，the hemoglobin level（ t = 2.641， P = 0.009）was lower，the length of hospital stay was longer，the rates of tracheal intubation，urinary catheter，and deep vein catheterization were higher（ Z = -4.243，-4.660，-5.341，-4.583，all P < 0.001），the duration of carbapenem and polymyxin B use was longer（ Z = -4.757，-7.554，both P < 0.001），the proportion of combined quinolone-resistant Escherichia coli（QREC）and carbapenem-resistant organism（CRO）infections and bloodstream infections，and the rate of admission to intensive care units was higher（ χ 2 = 33.737，42.041，5.426，12.991， P < 0.05 or < 0.01）. Multivariate analysis showed that time to polymyxin B use（ OR = 1.179， 95%CI 1.059-1.312， P = 0.003），combined QREC infection（ OR = 5.357， 95%CI 2.100-13.669， P < 0.001）and combined CRO infection（ OR = 3.302， 95%CI 1.146-9.514， P= 0.027）were independent risk factors for PR-CRKP. Conclusion:Prolonged use of polymyxin B is an independent risk factor for PR-CRKP，and mixed QREC and CRO infection can increase the risk of PR-CRKP.

Objective:To optimize the strategy of Nuss procedure with open approach via median sternotomy for pectus excavatum(PE) with congenital heart disease(CHD).Methods:25 PE patients with CHD treated in our center from January 2017 to November 2021 were reviewed and divided into two groups. The CHD surgery and open Nuss procedure with median sternotomy were performed concomitantly in 9 cases(group A), whose height of(121.7±28.0)cm, weight of(22.2±14.0)kg, age of(7.65±4.08) years old, and Haller index of 3.99±1.37. 16 cases underwent open Nuss procedure via median re-sternotomy after congenital heart surgery(group B), whose height of(130.9±27.2)cm, weight of(26.5±14.3)kg, age of(8.82±4.09) years old, and Haller index of 4.18 ± 0.97. The cardiac anatomy, cardiac function and the severity of PE of all patients were evaluated by echocardiography and computed tomography preoperatively. The preoperative gender, appearance of PE, types of associated CHD, retrosternal adhesion and the interval between open Nuss procedure and CHD surgery were collected. The details of operation, hospital stay, intraoperative adverse events, postoperative complications and follow-up were collected.Results:All the operations were accomplished successfully in 25 children. No intraoperative complications occurred. One had a postoperative wound infection in group A. The operation time of group A was significantly longer than that of group B[(3.78±1.54) h vs.(2.19±0.94) h, P<0.05]. There was no significant difference in the mechanical ventilation time between the two groups[(22.50±45.64) h vs.(4.18±1.41) h, P=0.263]. The ICU stay of group A was significantly longer than that of group B[(4.00±6.42) days vs.(1.13±0.34) days, P<0.05]. There was no significant difference in the length of hospital stay between the two groups[(16.00±15.18) days vs.(9.19±2.31) days, P=0.419]. The Nuss bar was removed in 14 cases of the two groups, with a interval of(27.9±11.25) months after open Nuss procedure, the postoperative Haller Index was 2.48±0.49. There was no difference of LVEF in postoperative and preoperative echocardiography(0.663±0.028 vs. 0.659±0.038, P=0.533). The FVC and FEV1 were significantly improved compared with before operation[(87.2±3.9)% vs.(84.1±8.2)%]. The outcome was good. Conclusion:For PE patients with CHD, one-stage or staged individualized Nuss procedure with open approach via median sternotomy can be performed after careful preoperative evaluation. A skillful median re-sternotomy and widely dissecting retrosternal adhesion between sternum and anterior wall of heart are necessary to avoid serious intraoperative complications such as massive heart bleeding and ensure good sternal elevation.