BACKGROUND: Naoxinqing capsule has been used for treating cerebral ischemia/reperfusion injury for a long time. However, there are relatively few in-depth studies on its mechanism. OBJECTIVE: To investigate the therapeutic effect of Naoxinqing Capsule on gerbil model of cerebral ischemia/reperfusion injury by molecular biological means. METHODS: The study was approved by the Laboratory Animal Ethical Committee of Liaoning University of Chinese Medicine, approval No. 21000092017072. Eighty male Mongolian gerbils were randomly divided into sham, model, Naoxinqing and Naoluotong groups, and the latter three groups underwent bilateral common carotid artery clip for 5 minutes, to establish the model of cerebral ischemia/reperfusion injury. The sham group received no common carotid artery clip. Next day, the sham group fed normally, the model group was given normal saline, Naoxinqing group was given the 100 mg/(kg•d) Naoxinqing via gavage, and Naoluotong group given 100 mg/(kg•d) Naoluotong via gavage, respectively, for 21 consecutive days. The water maze test was conducted at 1 week before experiment ended. The brain tissue was removed after experiment. The learning and memory function, hippocampal neurons, cerebrovascular and corresponding molecular changes were detected. RESULTS AND CONCLUSION: (1) Compared with the sham group, the learning ability in the model group was decreased significantly. Naoxinqing and Naoluotong groups could effectively improve the learning ability after surgery. (2) Compared with the model group, the numbers of neurons in the Naoxinqing and Naoluotong groups were increased significantly, arranged regularly with clear contour and complete structure. (3) Compared with the model group, in the Naoxinqing and Naoluotong groups, the activities of superoxide dismutase and lactate dehydrogenase, and glutathione content were significantly increased, and the content of malonaldehyde was significantly decreased (P < 0.01). (4) The expression levels of ASC, NLRP3 and Caspase-1 in the hippocampus in the Naoxinqing and Naoluotong groups were significantly lower than those in the model group (P < 0.05). (5) The levels of interleukin-18 and interleukin-1β in the Naoxinqing and Naoluotong groups were significantly lower than those in the model group (P < 0.01). (6) Compared with the model group, the cells positive for platelet endothelial cell adhesion molecule-1 in the Naoxinqing and Naoluotong groups were significantly increased, the cells contacted closely each other. (7) Compared with the model group, in the Naoxinqing and Naoluotong groups, the expression levels of platelet endothelial cell adhesion molecule-1 and phosphorylated endothelial nitric oxide synthase were significantly up-regulated, and the content of nitric oxide was significantly increased (P < 0.01). (8) These results indicate that Naoxinqing and Naoluotong can effectively protect the morphology of hippocampal CA1 region in gerbils. Cerebral ischemia/reperfusion injury is accompanied by cerebral vascular dysfunction. Naoxinqing Capsule can protect cerebral vascular function and inhibit cerebral ischemia/reperfusion injury.

Objective To investigate the effect of a decoction to nourish qi and invigorate the spleen on mitochondrial respiratory chain enzyme complex activity in cardiomyocytes of rats with spleen qi deficiency syndrome. Methods Rats were randomly divided into normal,model,and treatment groups. The model and treatment groups were treated by diet intervention combined with the limit swim method. The general condition and spleen qi deficiency syndrome were assessed on day 15. After the success of the model,the normal and model groups were treated with a con?ventional feeding method combined with normal saline ,and the treatment group was treated by diet intervention combined with a decoction to nour?ish qi and invigorate the spleen for 9 weeks. The activity of two mitochondrial respiratory chain enzyme complexes was observed. Results The ac?tivity of mitochondrial respiratory chain enzyme complexⅡand complexⅣin the model group was significantly lower than the activity in the nor?mal and treatment groups(P<0.05). The activity levels of complexⅡand complexⅣwere significantly different between the model group and the treatment group(P<0.05). Conclusion Spleen qi deficiency can cause decreased activity of mitochondrial respiratory chain enzyme com?plexes in myocardial cells. The decoction to nourish qi and invigorate the spleen can modulate the activity of myocardial mitochondrial respiratory chain enzyme complexesⅡandⅣ.

Objective To explore the effects of astragalus (AST),total flavone of astragalus (TFA),total saponins of astragalus (TSA) and astragalus polysaccharides (APS) on ischemia/reperfusion (40 min/60 min) injury in isolated guinea-pig heart.Methods Isolated guinea-pig hearts underwent ischemia,then followed by K-H perfusion (I/R group),AST (60 mg/L),AST (60 mg/L),TFA (60mg/L),TSA (60 mg/L) and APS (60 mg/L) perfusion (n =6 each).Isolated hearts without ischemia serve as control group (n =6).Activity of lactate dehydrogenas (LDH) and creatine kinase (CK) in effluent were measured.Infarct size,myocardial superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were also determined.Results Compared to control hearts,heart rate,coronary flow and myocardial superoxide dismutase (SOD) activity were significantly reduced,while LDH and CK in effluent as well as myocardial MDA were significantly increased in the I/R hearts during reperfusion (all P ＜ 0.05),these changes could be partly reversed by AST and TFA perfusion.Infarct size was also significantly reduced in AST (11.9 ± 2.03) ％ and TFA (13.31 ± 1.17) ％ treated hearts compared to that in I/R group(18.9 ±2.27) ％ (all P ＜ 0.01).Conclusions The findings indicate that AST and TFA could attenuate I/R injury in isolated guinea-pig heart possibly through enhancing the activity of SOD and reducing lipid peroxidation.

PURPOSE: Tuberculous pleurisy is the most frequent extrapulmonary manifestation of tuberculosis. In spite of adequate treatment, pleural fibrosis is a common complication, but the mechanism has not been elucidated. This study is to determine whether epithelial to mesenchymal transition (EMT) of mesothelial cells occurs in tuberculous pleurisy. MATERIALS AND METHODS: Normal pleural mesothelial cells, isolated from irrigation fluids during operations for primary spontaneous pneumothorax, were characterized by immunofluorescence and reverse transcription polymerase chain reaction (RT-PCR). These cells were treated in vitro with various cytokines, which were produced in the effluents of tuberculous pleurisy. The isolated cells from the effluents of tuberculous pleurisy were analyzed by immunofluorescence and RT-PCR analysis. RESULTS: The isolated cells from the irrigation fluid of primary spontaneous pneumothorax had epithelial characteristics. These cells, with transforming growth factor-beta1 and/or interleukin-1beta treatment, underwent phenotypic transition from epithelial to mesenchymal cells, with the loss of epithelial morphology and reduction in cytokeratin and E-cadherin expression. Effluent analysis from tuberculous pleurisy using immunofluorescence and RT-PCR demonstrated two phenotypes that showed mesenchymal characteristics and both epithelial & mesencymal characteristics. CONCLUSION: Our results suggest that pleural mesothelial cells in tuberculous pleurisy have been implicated in pleural fibrosis through EMT.
Cells, Cultured ; Epithelial Cells/*pathology ; Epithelial-Mesenchymal Transition/*physiology ; Fluorescent Antibody Technique ; Humans ; Pleura/*pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Tuberculosis, Pleural/*pathology

Objective To analyse the differential metabolites and related metabolic pathways in stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome by serum metabolomics.Methods This study observed 60 patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome and 60 healthy volunteers in the same period.Liquid chromatography-mass spectrometry(LC-MS)was performed on the serum metabonomics.The differential metabolites were identified by multivariate statistical analysis of the original spectrogram and original data,and enrichment analysis of KEGG metabolic pathway was analyzed.Results A total of 60 patients in the group of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome participated in the study,and a total of 60 healthy volunteers in the control group participated in the study.There was no statistical difference in general information and biochemical indicators between the two groups(P>0.05);Eighteen differential metabolites were found respectively,including phenylacetaldehyde,orthophosphate,guanosine,diethyl phosphate,2-dehydro-d-gluconate,guanine and 5-(2-hydroxyethyl)-4-methylthiazole down-regulated expression,taurocholate,2-propylglutaric acid,8-amino-7-oxononanoate,l-tyrosine,s-sulfo-l-cysteine,cyclohexanecarboxylic acid,porphobilinogen,(r)-acetoin,octanoylglucuronide,melatonin and solanine up-regulated expression,involving phenylalanine metabolism,thiamine metabolism,purine metabolism.Conclusion The differential metabolites reveal the metabolic essence of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome from the micro level,and can provide clues for clinical early warning of patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndromet.

BACKGROUND/AIMS: We investigated the incidence and prognosis of disseminated intravascular coagulation (DIC) using DIC scoring system in patients with severe sepsis or septic shock. METHODS: Patients admitted to the intensive care unit (ICU) in a tertiary hospital for severe sepsis or septic shock were enrolled from Mar. 2008 to Feb. 2009. Using the International Society on Thrombosis and Haemostasis (ISTH) criteria, we calculated DIC score at three time points (Day 0, Day 1, and Day 2). RESULTS: Among 111 patients with severe sepsis or septic shock, 89 (severe sepsis, 8; septic shock, 81) were enrolled. Mean DIC score at ICU admission was 3.3+/-1.3 and the incidence of overt DIC (DIC score > or = 5) during the first 48 hours was 33.8% (27/89). Sequential Organ Failure Assessment (SOFA) score was well correlated with DIC score and was higher in patients with overt DIC than in those without. The ICU, hospital and 28-day death rates in patients with overt DIC were 63.0%, 66.7%, and 63.0%, respectively, which were significantly higher than in those without overt DIC. In multivariate analysis, Simplified Acute Physiology Score (SAPS) II was significantly associated with hospital death (p=0.002), and the occurrence of overt DIC showed a borderline significance (p=0.053). CONCLUSIONS: Using the ISTH criteria for DIC, the incidence of overt DIC was 33.8% in patients with severe sepsis or septic shock. The occurrence of overt DIC was associated with a higher organ failure score and hospital outcomes.
Dacarbazine ; Disseminated Intravascular Coagulation ; Humans ; Incidence ; Intensive Care Units ; Multivariate Analysis ; Organ Dysfunction Scores ; Prognosis ; Sepsis ; Shock, Septic ; Tertiary Care Centers ; Thrombosis

Sarcoidosis is a systemic granulomatous disease that primarily affects the lung and lymphatic system of the body. Since Brincker first noted a statistically significant increase of malignant tumors among sarcoidosis patients, there have been several reports on simultaneously developed sarcoidosis and malignancy. A 30-year-old man was admitted to our hospital because of multiple enlarged mediastinal lymph nodes. The patient had been well until approximately 10 days before admission, when he developed a cough. Chest X-ray and computed tomography (CT) of the chest that were performed at the outpatient department revealed multiple enlarged mediastinal lymph nodes. Cervical lymph node biopsy revealed both non-caseating granuloma and metastatic papillary carcinoma, whereas the mediastinal lymph node showed only non-caseating granuloma. The thyroid gland surgical specimen showed papillary carcinoma. We report here on a case of a 30-year-old man who had sarcoidosis and thyroid cancer, and we include a review of the literature.
Adult ; Biopsy ; Carcinoma, Papillary ; Cough ; Granuloma ; Humans ; Lung ; Lymph Nodes ; Lymphatic System ; Outpatients ; Sarcoidosis ; Sarcoidosis, Pulmonary ; Thorax ; Thyroid Gland ; Thyroid Neoplasms

Objective This study used high-throughput sequencing technology to detect the regulation of JianPiHuaTan Prescription(JPHT)on the ApoE-/-mouse miRNA related to vascular smooth muscle cells proliferation and migration,verify the expression of related proteins,and explore the therapeutic effect of JPHT on atherosclerosis.Methods Ten of C57BL/6J mice were used as control group,and 30 ApoE-/-mice were randomly divided into model group,western medicine group and JPHT group.Sequencing technology was performed on aortic sample to select the differentially expressed miRNA.We screened out the tagetted miRNA related to VSMCs proliferation and migration.RT-qPCR and Western blot technology were used to test the differentially expressed miRNA and tagetted protein.Results Compared with model group,a total of 9 miRNAs were changed in JPHT group,among which 7 were up-regulated and 2 were down-regulated.The expression of miRNA-34a was up-regulated in JPHT group.The miRNA-34a and α-SMA protein expression in aorta of JPHT group were significantly different with model group by RT-qPCR and Western blot experiment(P<0.01).Conclusion Jianpi Huatan Prescription may improve ApoE-/-mice atherosclerosis through inhibitting the proliferation of vascular smooth muscle cells by regulating miRNA-34a.

Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinfor-matic tool for researchers to specifically identify such feature pairs. Here, we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3306 feature pairs in 16 human cell types, we reveal a dual role of CCCTC-binding factor (CTCF) in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, CTCF is required for the active marker H3K27ac in cell types requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity. The code for MACMIC is available at https://github.com/bxia888/MACMIC.

OBJECTIVES: To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology. METHODS: Six ApoE^－/－ mice were fed with a high-fat diet for 16 weeks as a comorbid model of NAFLD and AS (model group). Normal diet was given to 6 wildtype C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify differential metabolites. Network pharmacology was applied to explore the possible mechanistic effects of differential metabolites on AS and NAFLD. An in vitro comorbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. Cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively. RESULTS: A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1 and SCD. The Kyoto Encyclopedia of Genes and Genomes showed the top 10 signaling pathways were PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway, IL-17 signaling pathway and NAFLD. Experimental validation showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1 and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while the formation of foam cells aggravated mitochondrial damage. CONCLUSIONS Abnormal lipid metabolism and inflammatory response are distinctive features of comorbid AS and NAFLD. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of macrophage inflammatory response, resulting in the acceleration of AS development.
Animals ; Mice ; Non-alcoholic Fatty Liver Disease/metabolism* ; Cyclooxygenase 2/metabolism* ; PPAR gamma/metabolism* ; Reactive Oxygen Species/metabolism* ; Mice, Inbred C57BL ; Hepatocytes ; Macrophages/metabolism* ; Liver