Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

Objective To evaluate the effect of extracorporeal membrane oxygenation combined with intra-aortic balloon pump mechanical circulatory support for patients with cardiogenic shock complicating acute myocar-dial infarction during PCI process.Methods Patients with cardiogenic shock complicating myocardial infarction who underwent PCI in the hospital from January 2015 to December 2019 were selected.Those who were under support of extracorporeal membrane oxygenation combined with intra-aortic balloon pump were enrolled in the observation group,the patients under support of only intra-aortic balloon pump were selectedin the control group.The differ-ences of clinical features and prognosis were compared.Results A total of 40 patients were enrolled,11 were in the observation group and 29 in the control group.Compared with control group,more patients were complicated with old myocardial infarction(5/11 vs.2/29,P=0.016),more patients were diagnosed as non-ST elevated myocardial infarction(8/11 vs.11/29,P=0.049)and left ventricular ejecting fraction was lower[(38.5±10.10)vs.(48.55±8.86),P=0.01]in observation group.Moreover,the proportion of patients with EF＜35％was higher in the observation group(5/11 vs.3/29,P=0.01).The observation group has significantly higher rates of multi-vessel disease and Syntax scores compared to the control group(multi-vessel disease:10/11 vs.11/29,P=0.02;Syntax score:[(33.36±13.37)vs.(25.74±5.75),P=0.015];the observation group exhibited a higher proportion of patients achieving complete revascularization(9/11 vs.8/29,P=0.002).Mechanical complications were higher in observation group(6/11 vs.5/29,P=0.02),The survive rate in observation group is higher than that in control group(91.00％vs.55.17％,P=0.03)at one-year follow-up.Conclusion Compared with only IABP,ECMO com-bined with IABP hemodynamic support during PCI process for patients with cardiogenic shock complicating acute myocardial infarction enjoys more complete revascularization and better mortality outcome,although it has rela-tively higher mechanical complications.

Objective·To use single-cell RNA sequencing(scRNA-Seq)technology to interpret the cellular communication landscape of coronary atherosclerosis(CA),and to explore the dominant cell subsets and their key genes.Methods·The GSE131778 data set was downloaded and preprocessed,and quality controlling,dimension reduction clustering and annotation were carried out.Then cell communication analysis was conducted by using CellChat package to identify dominant cell subsets.The FindAllMarker function was used to screen differentially expressed genes(DEGs)between the dominant cell subpopulation and other cell subpopulations,and its protein-protein interaction(PPI)network was constructed.The DEGs ranked in the top five of the Degree algorithm were taken as key genes.Then,the key genes were matched and mined with the cell communication network analyzed by CellChat to obtain the ligand-receptor pairs(L-R)and the signal pathways mediated by the key genes,and the results were visualized.At the same time,the atherosclerosis mouse model was constructed and RT-PCR was used to detect the expression of key genes in carotid atherosclerosis lesions.Results·A total of 11 cell subsets were identified in CA lesions,including smooth muscle cells,endothelial cells,macrophages,monocytes,etc.Cell communication results showed that CellChat detected 70 significant L-R and 26 related signal pathways in 11 cell subsets.Smooth muscle cell was the dominant cell subgroup with the most significant interaction frequency and intensity with other cell subgroups in the active state of communication.The results of DEGs screening showed that there were 206 DEGs between smooth muscle cell subsets and other cell subsets,among which ITGB2,PTPRC,CCL2,DCN and IGF1 were identified as key genes.The results of cell communication mediated by key genes showed that CCL2 and ACKR1 formed L-R and participated in the communication network between smooth muscle cells and endothelial cells through mediating CCL signaling pathway.ITGB2 formed receptor complexes with ITGAM and ITGAX respectively,and then formed L-R with C3 to mediate the complement signal pathway,participating in the communication network among smooth muscle cells,macrophages and monocytes.The validation results of hub genes in animal experiments were consistent with the results of bioinformatics analysis.Conclusion·Smooth muscle cells are the dominant cells in the pathological process of CA,and have extensive communication networks with other cells.They can construct cellular communication networks with endothelial cells,macrophages and monocytes through CCL and complement signaling pathways mediated by CCL2-ACKR1,C3-(ITGAM+ITGB2)and C3-(ITGAX+ITGB2).

Objective:By analyzing the cost change trend,internal structure change and main influencing factors of diabetes inpatients'hospitalization expenses,it provides empirical basis for promoting the reform of medical service prices,optimizing the internal structure of hospitalization expenses,effectively controlling hospitalization expenses,and reducing the economic burden of diabetes inpatients.Methods:Using the first page data of medical records of 13 426 diabetes inpatients in the target hospital from 2017 to 2021,it analyzes the structural change of diabetes inpatients'hospitalization expenses by using structural change degree and grey correlation degree methods,and analyzes the influencing factors of hospitalization expenses by using linear regression and BP neural network model.Results:Drug expenses and medical technology expenses are the top two in the proportion of total hospitalization expenses of discharged patients with diabetes,and they account for a large proportion in the total hospitalization expenses.The results of structural change and grey correlation show that drug expenses and medical technology expenses are these two factors that cause changes in the total hospitalization cost structure and have a high correlation with the total hospitalization cost,with a cumulative contribution rate of 90.50％.According to the results of linear regression and neural network model,the length of stay is the most important factor affecting the total cost of hospitalization of diabetes patients,followed by the number of operations/procedures and diagnoses.Conclusion:The internal composition of hospitalization expenses for diabetes patients is unreasonable.The proportion of drug expenses and medical technology expenses is too high.The proportion of medical and nursing expenses reflecting the technical labor value of medical personnel is relatively low.The structure of medical income needs to be further optimized.The length of stay is the most critical factor affecting the hospitalization expenses of diabetes patients.Reasonable control of the length of stay can effectively control the unreasonable growth of medical expenses and reduce the economic burden of diabetes patients.

Objective To evaluate the effect of extracorporeal membrane oxygenation combined with intra-aortic balloon pump mechanical circulatory support for patients with cardiogenic shock complicating acute myocar-dial infarction during PCI process.Methods Patients with cardiogenic shock complicating myocardial infarction who underwent PCI in the hospital from January 2015 to December 2019 were selected.Those who were under support of extracorporeal membrane oxygenation combined with intra-aortic balloon pump were enrolled in the observation group,the patients under support of only intra-aortic balloon pump were selectedin the control group.The differ-ences of clinical features and prognosis were compared.Results A total of 40 patients were enrolled,11 were in the observation group and 29 in the control group.Compared with control group,more patients were complicated with old myocardial infarction(5/11 vs.2/29,P=0.016),more patients were diagnosed as non-ST elevated myocardial infarction(8/11 vs.11/29,P=0.049)and left ventricular ejecting fraction was lower[(38.5±10.10)vs.(48.55±8.86),P=0.01]in observation group.Moreover,the proportion of patients with EF＜35％was higher in the observation group(5/11 vs.3/29,P=0.01).The observation group has significantly higher rates of multi-vessel disease and Syntax scores compared to the control group(multi-vessel disease:10/11 vs.11/29,P=0.02;Syntax score:[(33.36±13.37)vs.(25.74±5.75),P=0.015];the observation group exhibited a higher proportion of patients achieving complete revascularization(9/11 vs.8/29,P=0.002).Mechanical complications were higher in observation group(6/11 vs.5/29,P=0.02),The survive rate in observation group is higher than that in control group(91.00％vs.55.17％,P=0.03)at one-year follow-up.Conclusion Compared with only IABP,ECMO com-bined with IABP hemodynamic support during PCI process for patients with cardiogenic shock complicating acute myocardial infarction enjoys more complete revascularization and better mortality outcome,although it has rela-tively higher mechanical complications.

Objective:To investigate the expression profile of IL-36 family members in patients with coronary atherosclerotic heart disease (CAHD) and to assess the regulatory effects of exogenous IL-36 on CD8 + T cell function in CAHD patients. Methods:Twenty controls and 82 CAHD patients including 31 with stable angina pectoris (SAP), 27 with unstable angina pectoris (UAP) and 24 with acute myocardial infarction (AMI) were enrolled in this study. Anti-coagulant peripheral blood samples were collected. Plasma and peripheral blood mononuclear cells were isolated. The levels of IL-36α, IL-36β, IL-36γ and IL-36 receptor antagonist (IL-36RA) in plasma were measured by ELISA. CD8 + T cells were enriched. The expression of IL-36 receptor subunits at mRNA level was semi-quantified by real time PCR. Flow cytometry was used to detect the expression of programmed death-1 (PD-1), cytotoxic T lymphocytes associated protein-4(CTLA-4) and lymphocyte-activation gene-3 (LAG-3) in CD8 + T cells. Levels of periforin, granzyme B, granulysin, IFN-γ and TNF-α in the culture supernatants of CD8 + T cells were measured by ELISA. Purified CD8 + T cells from controls and AMI patients were stimulated with recombinant human IL-36RA. Changes in the expression of immune checkpoint molecules and the secretion of cytotoxic molecules and cytokines after IL-36RA stimulation were analyzed. One-way analysis of variance or paired t-test was used for statistical analysis. Results:There were no significant differences in plasma IL-36α, IL-36β or IL-36γ level between the control, SAP, UAP and AMI groups ( P>0.05). Plasma IL-36RA level was significantly down-regulated in the AMI group as compared with that in the control, SAP and UAP groups[(1 159.57±297.83) pg/ml vs (1 773.47±754.29) pg/ml, (1 600.12±740.48) pg/ml and (1 578.72±720.42) pg/ml; P<0.05]. The expression of IL-1 receptor 6 (IL-1R6) and IL-1 receptor accessory protein (IL-1RAcP) at mRNA level, the expression of PD-1 and CTLA-4, and the secretion of IFN-γ and TNF-α by CD8 + T cells showed no significant differences between the four groups ( P>0.05). Periforin, granzyme B and granulysin levels secreted by CD8 + T cells of the AMI group were significantly higherthan those of the control, SAP and UAP groups ( P<0.05). In the control group, recombinant human IL-36RA stimulation did not affect the expression of immune checkpoint molecule or the secretion of cytotoxic molecules and cytokines by CD8 + T cells ( P>0.05). In the AMI group, the percentage of PD-1 + CD8 + T cells increased after recombinant human IL-36RA stimulation ( P=0.033), but no significant change in the percentage of CTLA-4 + CD8 + T cells was observed ( P=0.288). Moreover, recombinant human IL-36RA stimulation suppressed the CD8 + T cells of AMI patients to secrete periforin, granzyme B and granulysin ( P<0.05), but not affect the secretion of IFN-γ and TNF-α ( P>0.05). Conclusions:The reduced IL-36RA level in AMI patients might induce the enhancement of CD8 + T cell activity by promoting CD8 + T cells to secrete cytotoxic molecules, which was involved in the immunopathogenesis of AMI.

Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.

Objective:To document the clinical efficacy of supplementing intra-articular injection of sodium hyaluronate with Baduanjin exercise in the treatment of knee osteoarthritis (KOA).Methods:Forty patients with KOA were randomly divided into an observation group and a control group, each of 20. Both groups received health education and intra-articular injection of sodium hyaluronate once a week for 5 consecutive weeks. The observation group additionally underwent Baduanjin exercise 3 times a week for the 5 weeks. Before and after the treatment, knee joint function, pain and surface integrated electromyography (iEMG) values of the affected quadriceps were assessed using the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index Scale, and a visual analogue scale (VAS).Results:After the treatment the average VAS and WOMAC scores of both groups had decreased significantly, while the average iEMG value of the quadriceps on the affected side had increased significantly. The average VAS and WOMAC scores of the observation group were significantly lower than the control group′s averages after the treatment, while the average iEMG value of the quadriceps on the affected side was significantly higher.Conclusion:Combining Baduanjin exercise with sodium hyaluronate joint injection in the treatment of KOA has a synergistic effect which can better relieve knee pain, improve knee functioning, and delay the progression of KOA. The combined treatment is worthy of clinical promotion and application.

Objective? To investigate the effects of nursing quality improvement in chest pain center on patients with ST-segment elevation myocardial infarction (STEMI). Methods? A total of 93 patients with STEMI who received routine nursing care from July to December 2016 (n=30) and optimized quality nursing care from January to July 2017 (n=63) in the First Affiliated Hospital of He＇nan University of Traditional Chinese Medicine were enrolled to the study. The patients＇ gender, age, and 18-lead ECG completion time, Door-To-Balloon time (D2B), myocardial injury marker report time, and their hospitalization days (d), were compared between the two groups. Results? The differences in the indicators including sex,age and 18-leads ECG completion time were not statistically different (P＞0.05). However, the differences in hospitalization time, D2B time, and myocardial injury marker report time had statistical significance (P＜ 0.05). Conclusions? The optimizing project of nursing quality management, including the optimization of nursing document writing, specialized instrument operation process and ward management index, can reduce patients＇ hospital stay, D2B time, and myocardial injury marker report time, hence improve the overall treatment quality for the patients.