1.Molecular Mechanism of Danshen Tongluo Formula in Intervention of Coronary Artery Disease-dominated Panvascular Disease
Jiawen CHENG ; Chao LIU ; Jie WANG ; Yongmei LIU ; Wenjing LIAN ; Chengzhi HOU ; Chenyang ZHU ; Cheng MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):86-93
ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group, a model group, and a Danshen Tongluo formula (28 mg·kg-1·d-1) group. The efficacy was evaluated by examining the cardiac ultrasound, determination of the plasma level of N-terminal pro-brain natriuretic peptide, and pathological staining. After single-cell sequencing, SingleR package, public datasets, and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis, and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide ( NT-proBNP ) level (P<0.05), ameliorated myocardial cell damage and fibrosis, and increase left ventricular ejection fractions (LVEF) in the rat model of heart failure after myocardial infarction(P<0.05). Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells, venous endothelial cells, and capillary-arterial endothelial cells, while reducing the proportion of capillary-venous endothelial cells. In addition, this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells, while downregulating Mif-(CD74+CXCR44) signaling in endothelium-M1 macrophages and Mif-(CD74+CD44) signaling in endothelium-M2 macrophages. It reduced the citric acid cycle, oxidative phosphorylation, and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells, venous endothelial cells, and venous capillary endothelial cells can all regulate oxidative phosphorylation, cell adhesion molecules, and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.
2.Effects of modified Xuanfuhua Decoction on pain behavior and p38MAPK signaling pathway-mediated spinal cord neuroinflammation in rats with sciatic nerve injury
Yuanyuan HOU ; Yalun FENG ; Dou WANG ; Wenying XUE ; Yongmei YAN
International Journal of Traditional Chinese Medicine 2024;46(4):451-457
Objective:To observe the effects of modified Xuanfuhua Decoction on pain behaviour and spinal cord neuroinflammation mediated by phosphorylated mitogen-activated protein kinase p38 (p38MAPK) signaling pathway in rats with sciatic nerve injury; To analyse the mechanism of its effects.Methods:Totally 108 SD rats were randomly divided into sham-operation group, model group, pregabalin group, decoction low-, medium- and high-dosage groups, with 18 rats in each group. The CCI model was established by ligation of sciatic nerve in other groups except sham-operation group. On the postoperative day, the decoction low-, medium-, high-dosage groups were gavaged with 2.5, 5.0 and 10.0 g/kg of modified Xuanfuhua Decoction concentrate, respectively. The pregabalin group was gavaged with 15 mg/kg of pregabalin. The sham-operation group and the model group were gavaged with equal amounts of saline once/d for 15 days. Pain behavioural assays were performed before, on the 3rd, 7th, 11th and 15th day of administration respectively. The levels of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α), IL-10 were detected by ELISA method. The expressions of Toll-like receptor 4 (TLR4), nuclear factor-κB p65 (NF-κB p65) were detected by immunohistochemistry staining. The phosphorylated p38MAPK (p-p38MAPK) were measured in the spinal cord by Western blot.Results:Compared with the model group, the scores of spontaneous pain in decoction high-dosage group decreased ( P<0.05), the thermal foot shrinkage latency (TWL) was prolonged ( P<0.05), and the mechanical foot shrinkage reflex threshold (MWT) increased ( P<0.05); the levels of IL-1β and TNF-α in spinal cord tissue of decoction low-, medium- and high-dosage groups decreased ( P<0.05), the level of IL-10 increased ( P<0.05), the average gray values of TLR4 and NF-κB p65 in spinal cord decreased ( P<0.05), and the expression of P-P38MAPK protein decreased ( P<0.05). Conclusion:Modified Xuanfuhua Decoction can effectively improve neurogenic pain in CCI rats, and the mechanism may be related to inhibition of p38MAPK-TLR4 signaling pathway activation-mediated spinal cord neuroinflammation.
3.Differential metabolites of bronchoalveolar lavage fluid from coal worker's pneumoconiosis patients
Chaoyi MA ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Gang CHEN ; Guoxuan MA ; Yongmei ZHAO ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xiaolu LIU ; Xinyu LI
Journal of Environmental and Occupational Medicine 2024;41(6):617-624
Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.
4.Changes in intestinal flora of coal workers' pneumoconiosis patients after tetrandrine intervention
Xiaolu LIU ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Yongmei ZHAO ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xinyu LI ; Chaoyi MA
Journal of Environmental and Occupational Medicine 2024;41(6):625-631
Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P<0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P<0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P<0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P<0.05), but the differences in Chao1 index were not statistically significant (P>0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P>0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P<0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P<0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.
5.Targeting histone deacetylases for cancer therapy: Trends and challenges.
Tao LIANG ; Fengli WANG ; Reham M ELHASSAN ; Yongmei CHENG ; Xiaolei TANG ; Wengang CHEN ; Hao FANG ; Xuben HOU
Acta Pharmaceutica Sinica B 2023;13(6):2425-2463
Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.
6.Relationship between different types of helicobacter pylori infection and metabolic syndrome in healthy people
Junyuan LIU ; Yongmei HE ; Xiaolin HOU ; Meihua CUI
Clinical Medicine of China 2021;37(6):555-559
Objective:To explore the relationship between different types of helicobacter pylori (Hp) infection and metabolic Syndrome (MS) in healthy population.Methods:The data of 4 602 adults who underwent physical examination in the Space Center Hospital from January to December 2019 were collected for research, the serum Hp antibody typing was detected by immunoblotting, and the results of liver ultrasound and blood biochemical examination were collected for statistical analysis.Results:Among the physical examination population,there were 2 018 cases with positive serum Hp antibody and 2 584 cases with negative serum Hp antibody.According to the expression of cytotoxin-associated gene A protein (CagA) and vacuolar toxin, 2 018 patients with positive serum Hp antibody were divided into 1 088 cases in type Ⅰ group (53.9%(1 088/2 018)) and 930 cases in type Ⅱ Group (46.1%(930/2 018)). There were significant differences in age, systolic blood pressure and prevalence of nonalcoholic fatty liver disease (NAFLD) between type Ⅰ group and type Ⅱ Group ( P<0.05). There was no significant difference in gender, fasting blood glucose, triglyceride,high-density lipoprotein cholesterol (HDL-C), diastolic blood pressure, body mass index (BMI) and waist circumference between the two groups ( P>0.05). There was no significant difference in the prevalence of ms between the two groups (18.3% (199/1 088)) and 19.0%(177/930), P=0.670). Multivariate logistic regression analysis showed that there was no correlation. between different serum Hp antibody typing and MS ( OR=1.194,95% CI 0.842-1.693, P=0.319). Conclusion:Different subtypes of type Ⅰ and type Ⅱ Hp infection are not distinctly associated with metabolic syndrome.
7.Effect of scenario simulation nursing in fundus fluorescein angiography of preschool children
Jian WANG ; Junjun HOU ; Juan XIE ; Xin CHANG ; Jia HOU ; Yongmei WANG
Chinese Journal of Modern Nursing 2021;27(33):4601-4603
Objective:To explore the effect of scenario simulation nursing in fundus fluorescein angiography (FFA) examination of preschool children.Methods:From January 2017 to March 2021, 98 preschool children who underwent FFA examination in the Fluorescence Contrast Room of Shanxi Eye Hospital were selected as the research object. Children from 2017 to December 2018 were in the control group with routine nursing, and children from January 2019 to March 2021 were in the experimental group with scenario simulation nursing. The incidence of adverse reactions and satisfaction with cooperation were compared between the two groups of children.Results:The incidence of adverse reactions in children in the experimental group was 2.00%, which was lower than 16.67% in children in the control group. The satisfaction with cooperation in the experimental group was 94.0%, which was higher than 79.2% in the control group. The differences were all statistically significant ( P<0.05) . Conclusions:The application of scenario simulation nursing in FFA examination of preschool children can effectively reduce the incidence of adverse reactions in children and improve the satisfaction of children with cooperation during the examination.
8.Construction of a clinical nursing standard of shoulder-hand syndrome after stroke based on Delphi expert consultation
Heli ZHANG ; Yongmei LUO ; Shuxiao HOU ; Zhiying HAN ; Baohua LI
Chinese Journal of Modern Nursing 2021;27(1):24-30
Objective:To form a nursing standard for shoulder-hand syndrome (SHS) after stroke in accordance with the clinical situation by expert argumentation in the best evidence systematically retrieved and screened for SHS after stroke with the method of Delphi expert consultation.Methods:According to the level of evidence, we systematically retrieved and screened relevant guidelines, evidence summary, systematic reviews, original studies and expert consensus. Two researchers who had received Joanna Briggs Institute (JBI) evidence-based training used the Appraisal of Guidelines for Research & Evaluation (AGREE) Ⅱ, JBI quality evaluation tools for systematic reviews, randomized controlled trials/experimental studies and expert consensus to evaluate the included guidelines, systematic reviews, original studies and expert consensus. The included literature was classified and summarized, and recommendations and conclusions related to SHS after stroke were screened and extracted. According to the results of the literature summary, the first draft of the clinical nursing standard for SHS after stroke was formed. Using the Delphi method, 25 experts in related fields were selected for two rounds of expert consultation to demonstrate the contents of the first draft.Results:This study included 8 guidelines including 1 evidence summary, 2 systematic reviews, 7 original studies and 2 expert consensus. The overall quality of the guidelines was Grade B; one piece of evidence summary was of good quality and was Grade B; the overall quality of two systematic reviews was low, and the overall quality of seven original studies was average. The first draft of the clinical nursing standard for SHS after stroke included 6 content frameworks and 29 recommendations. Two rounds of expert consultation were conducted, the questionnaire response rates were 89.28% and 100%, and the expert authority coefficients were 0.864 and 0.894, respectively. The Kendell's W of important content framework and recommended in the second round of expert consultation were 0.118 ( P<0.05) and 0.188 ( P<0.001) . According to the results of the expert consultation, the clinical nursing standard for SHS after stroke was formed, including 6 content frameworks and a total of 31 recommendations. Conclusions:The clinical nursing standard for SHS after stroke is based on the best available evidence and expert argumentation, which is in line with the clinical situation in my country and can be sed in clinical nursing work.
10.Research status and progress of shift work sleep disorders in nurses
Siwei ZHANG ; Shuxiao HOU ; Yongmei LUO ; Baohua LI
Chinese Journal of Modern Nursing 2020;26(28):3995-4000
Nurse is one of the most common occupations in shift work. Due to the particularity of nursing work, shift work often causes nurses to suffer from shift work sleep disorders. It will not only lead to an increase in the risk of accidents in work, but also increase the incidence of nursing errors, and even seriously harm the physical and mental health of individual nurses. This paper reviews the prevalence, serious harm, related influencing factors and intervention measures of shift work sleep disorders among nurses at home and abroad, in order to expect nursing managers and nurses to raise their awareness and pay attention to shift work sleep disorders, thereby improving professional identity and happiness of nurses.

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