Discussion on the Scientific Connotation of Fortifying Spleen， Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein / 中医杂志

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Effects of Shenqi Gualou Xiebai Banxia Decoction （参芪瓜蒌薤白半夏汤） on PPARγ， Bile Acids， and Blood Lipids in Mouse Models of Atherosclerosis / 中医杂志

ObjectiveTo explore the mechanism of Shenqi Gualou Xiebai Banxia Decoction （参芪瓜蒌薤白半夏汤， SGXBD） in the treatment of atherosclerosis. MethodsThirty Apolipoprotein E gene knockout （ApoE-/-） mice were randomly divided into five groups： model group， rosuvastatin group， low-， moderate-， and high-dose SGXBD， with six mice in each group. They were fed a high-fat diet to prepare for atherosclerosis model. Another six C57BL/6J wild-type mice were set as the blank group. After modeling， the low-， moderate-， and high-dose SGXBD groups were gavaged with 6.46， 12.92， and 25.84 g/（kg·d） of SGXBD， respectively. The rosuvastatin group was given 1.55 mg/（kg·d） of rosuvastatin tablets by gavage. The blank group and model group were given 0.5 ml saline by gavage. After four weeks， the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum of each group were detected， as well as TC and TG in the liver. The serum bile acid level was detected by enzyme cycling colorimetry. The mRNA and protein expression of peroxisome proliferator-activated receptor γ （PPARγ）， sterol regulatory element-binding protein 2 （SREBP2）， 3-hydroxy-3-methylglutaryl-CoA reductase （HMGCR）， and cholesterol 7α-hydroxylase （CYP7A1） in the liver were detected by real-time RT-PCR and Western blot. ResultsCompared with the blank group， the model group showed significant increases in serum TG， TC， and LDL-C levels， and significant decreases in HDL-C and bile acid levels； the levels of TG and TC in the liver， as well as the expression of SREBP2 and HMGCR proteins and mRNA in the liver significantly increased， while the expression of PPARγ and CYP7A1 proteins and mRNA significantly decreased （all P＜0.01）. Compared with the model group， the rosuvastatin group and high-dose SGXBD group showed significant decreases in serum TG， TC， and LDL-C levels and liver TG and TC levels， and significant increases in bile acid levels； the expression of PPARγ and CYP7A1 proteins and mRNA increased， while the expression of SREBP2 and HMGCR proteins and mRNA decreased； the low-dose SGXBD group showed significant decreases in serum TC and LDL-C levels and liver TC level （P＜0.05 or P＜0.01）. Compared with the rosuvastatin group， the low-dose SGXBD group had a significantly higher liver TC level， while the high-dose SGXBD group had a significantly lower liver TC level， CYP7A1 mRNA level， and PPARγ protein expression level， and a significantly higher SREBP2 protein expression level （P＜0.05 or P＜0.01）. Compared with the low- and moderate-dose groups， the high-dose SGXBD group had significantly lower serum TG and liver TC levels （P＜0.05）. ConclusionSGXBD may improve blood lipid levels and exhibit anti-atherosclerotic effects by regulating the protein level of PPARγ and simultaneously affecting the synthesis of liver cholesterol and the conversion of cholesterol to bile acids.

Synergistic effects of Linggui zhugan decoction regulating autophagy on doxorubicin against non-alcoholic fatty liver disease-hepatocellular carcinoma / 中国药房

OBJECTIVE To explore the enhancement effect of Linggui zhugan decoction （LGZG） regulating autophagy on doxorubicin （DOX） against non-alcoholic fatty liver disease-hepatocellular carcinoma （NAFLD-HCC）. METHODS C57BL/6 mice were randomly divided into blank group， NAFLD-HCC group， LGZG group， DOX group and DOX+LGZG group， with 10 mice in each group. The NAFLD-HCC model was established by intraperitoneal injection of diethylnitrosamine （50 mg/kg） and high-fat diet. The blank group was injected with the same amount of normal saline and fed with ordinary diet. After modeling， administration groups were given LGZG aqueous extract （20 g/kg） intragastrically and/or DOX solution intraperitoneally （8 mg/kg）； the blank group and NAFLD-HCC group were given a constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. The general condition of mice （No.2022-BS-197） was monitored during modeling and drug intervention. After drug intervention， body weight， liver weight and liver coefficient of mice were detected. The histopathologic morphology and fibrosis degree of liver tissue in mice were observed； the levels of blood lipid [the levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C）]， the serum contents of alpha fetoprotein （AFP） and carcinoembryonic antigen （CEA）， and the expressions of marker of proliferation Ki-67， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X （Bax） in liver tissue were all detected as well as protein expressions of microtubule-associated proteins 1A and 1B （LC3）， Beclin1 and selective autophagy adopt proteins P62. RESULTS Compared with the blank group， the activity of mice decreased gradually as time in the NAFLD-HCC group； mental fatigue， disheveled and matte hair were observed， and body weight decreased significantly （P＜0.05）； liver weight had an upward trend， and liver coefficient increased significantly （P＜0.05）. The inflammatory cells of liver tissue were infiltrated， with some cells showing ballooning and small cell hyperplasia， and the degree of liver fibrosis was worsened； serum levels of TC， TG and LDL-C， AFP and CEA contents increased significantly， while HDL-C level decreased significantly （P＜0.05）. The protein expressions of Ki-67 and Bcl-2 in liver tissue were increased significantly （P＜0.05）， while the protein expression of Bax decreased. The protein expression of Beclin1 in liver tissue decreased significantly （P＜0.05）； LC3Ⅱ/ LC3Ⅰ decreased， while the expression of P62 protein increased. Compared with the NAFLD-HCC group， the above indexes of mice were improved to different extents in the DOX group， LGZG group and DOX+LGZG group， and the intervention effect of DOX combined with LGZG were better than those of DOX. CONCLUSIONS LGZG combined with DOX can synergically promote the apoptosis of tumor cells， enhance the sensitivity of NAFLD-HCC chemotherapy， and effectively slow down the occurrence and development of NAFLD-HCC. The mechanism may be related to the regulation of autophagy in tumor cells.

Study on the mechanism of Gynostemma pentaphyllum intervention on atherosclerosis based on network pharmacology / 国际中医中药杂志

Objective:To explore the mechanism of Gynostemma pentaphyllum in the treatment of atherosclerosis (AS) based on network pharmacology. Methods:TCMSP was used to analyze the chemical components and targeted effect of Gynostemma pentaphyllum, through the database like OMIM, TTD, drugbank and digsee to predict and screen the targeted effect of AS. The genes corresponding to the target were queried by UniProt database, and then the compound target (gene) network and protein-protein interaction network (PPI) were constructed by using Cytoscape 3.2.1 to screen out the core target. Finally, the function enrichment analysis of Gene Ontology (GO) and the pathway enrichment analysis based on Kyoto Encyclopedia of genes and genomes (KEGG) were carried out by David, and the mechanism of action was studied. Results:The compound-target network consisted of 13 compounds and 150 corresponding targets. The key targets were PGR, NR3C2, NCOA2, PPARG, PTGS1, PTGS2, etc. PPI network contains 131 proteins and 46 core proteins. There are 480 GO item in GO function enrichment analysis, including 403 entries in biological process (BP), 35 entries in cell composition (CC), and 42 entries in molecular function (MF). 25 signaling pathways related to AS were obtained by enrichment and screening of KEGG pathway, involving PI3K-AKT, TNF, HIF-1, MAPK, toll like receptor and other signaling pathways.Conclusions:This paper discussed the mechanism of Gynostemma pentaphyllum in the treatment of AS through network pharmacology, which provides new ideas and methods for further research and exploration of the mechanism of Gynostemma pentaphyllum in the treatment of AS.

Effects of Fear of Malpractice and Organizational Support on Job Burnout among Doctors / 中国医科大学学报

Objective To explore the relationship between fear of malpractice and job burnout and investigate the mediating role of organizational support in order to provide a theoretical basis for improving doctors'mental health. Methods A total of 1 800 doctors were selected from 8 hospitals of 5 cities in Liaoning province from June to July 2015. Questionnaires included those on personal information, fear of malpractice, organizational support, and job burnout. Additionally, the effective response rate was 1 399. The effects of fear of malpractice and organizational support on job burnout was explored using multiple hierarchical regression analysis. Asymptotic and resampling strategies were used to examine the mediating role of psychological capital between fear of malpractice and job burnout. Results Fear of malpractice was positively associated with emotional exhaustion and depersonalization, and organizational support was negatively associated with emotional exhaustion and depersonalization. Organizational support mediated the relationships between fear of malpractice and emotional exhaustion (0. 2, 95％CI: 0. 15-0. 25) and depersonalization (0. 1, 95％CI:0. 07-0. 13). Conclusion Fear of malpractice and organizational support may have an effect on doctors ' job burnout. In addition, organizational support may have a mediating effect on the relationship between fear of malpractice and job burnout.

Correlation between autophagy and polarization of macrophages in atherosclerosis plaque in arteriosclerosis obliterans amputees / 药学学报

This study was designed to investigate the correlation between autophagy and polarization of macrophages in atherosclerosis (AS) plaque in arteriosclerosis obliterans amputees. Femoral artery specimens from arteriosclerosis obliterans amputees were performed hematoxylin and eosin (HE) staining, oil red O and immunofluorescence staining to observe the morphology of atherosclerotic plaque, phenotype of macrophages and autophagy in plaque; using real-time quantitative RT-PCR technology to detect the mRNA level of M1 and M2 type markers in arterial tissue; to analyze polarized signal pathway and autophagy protein levels in macrophages by Western blotting. Arterial specimens staining showed obvious lipid deposition and obvious infiltration of amount of foam cells and inflammatory cells. Macrophages were mainly expression M1 type in percentage in fibrous plaque. Although both M1 and M2 macrophages were upregulated in atheromatous plaque, the increase was dominant in M2 type in percentage. The level of autophagy was significantly higher in the atheromatous plaque than that of fibrous plaque. The expression of tumor necrosis factor- α (TNF-α), monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and interleukin-12 (IL-12) mRNA was significantly higher in fibrous plaque than that of atheromatous plaque (P < 0.01 or 0.05), and arginase-1 (Arg-1), transforming growth factor-β (TGF-β), CD163 and interleukin-10 (IL-10) mRNA was significantly lower than that in atheromatous plaque (P < 0.01). The levels of p-STAT1 and NF-κB were significantly increased in fibrous plaque (P < 0.01), while p-STAT6 expression was significantly increased in atheromatous plaque (P < 0.01). The level of LC3-II was significantly higher in atheromatous plaque than that in fibrous plaque (P < 0.01). Macrophages in early atherosclerotic plaque were induced to M1 type through p-STAT1/NF-κB pathway and expressed moderate levels of autophagy; while macrophages in advanced plaques were induced to polarization of M2 type through p-STAT6 pathway. M2 macrophages expressed a higher level of autophagy than M1 macrophages.

Study on Anti-tumor Effects of Vinblastine Hydrophilic Group Modified Cationic Liposomes in Tumor-bearing Mice / 中国药房

OBJECTIVE:To study the anti-tumor effects of Vinblastine (VLB) hydrophilic group modified cationic liposomes in tumor-bearing mice. METHODS:Tumor-bearing model were induced by inoculating yellow ascites of S180 ascites tumor mice. Tumor-bearing mice were randomly divided into model group,VLB sulfate injection group,VLB liposomes group,VLB hydrophil-ic group modified liposomes group,VLB cationic liposomes group and VLB hydrophilic group modified cationic liposomes group, i.e. group A,B,C,D,E and F,with 18 mice in each group. Group A was given normal saline intravenously via mice tail,other groups were given VLB 1.5 mg/kg every 2 days for consecutive 5 times. The anti-tumor effects of different VLB preparations were compared,using living conditions,survival time,tumor volume and weight,and tissue pathological section as indexes. RE-SULTS:Compared with group A,B,C,D and E,the mice of group F were more active,and had longer survival time,smaller tumor volume and lighter tumor weight,with statistical significance(P<0.05). The tissue pathological section of mice in group F indicated that coagulation necrosis,disintegration,and dissolution of tumor cell nucleus. CONCLUSIONS:VLB hydrophilic group modified cationic liposomes have obvious anti-tumor effect,which are better than other VLB preparations.

Fundamental Research on Antiatherosclerotic Effect of Tanshinone ⅡA / 中国中医药信息杂志

Tanshinone ⅡA is one of the main effective components in Salviae Miltiorrhizae Radix et Rhizoma. It plays a role in the resistance to atherosclerosis by participating in anti-inflammatory in vascular wall, such as the regulating endothelial cell apoptosis and correcting lipid metabolism disorder. This article summarized recent researches of the basic role of tanshinone ⅡA in the resistance to atherosclerosis and provided references for clinical application of antiatherosclerotic effect of tanshinone ⅡA.

Application of hepatic stem cell transplantation to liver disease treatment / 中国组织工程研究

BACKGROUND:At present,the problems such as serious shortage of donor liver organs for transplantation,surgical injury,high incidence of surgical complications,as well as the high costs limit the development of liver transplantation,while the hepatic stem cell(HSC)transplantation provides a new pathway for the treatment of end-stage liver disease.OBJECTIVE:To introduce the source and classification of HSCs,research progress and problems of HSC transplantation for treatment of end-stage liver disease,and the clinical application prospects of HSC transplantation.METHODS:Articles were collected from CNKI and Medline database with the keywords of "hepatic stem cells,liver disease,transplantation" in both Chinese and English from 1999 to 2009.Among 87 articles,30 were included according to inclusion and exclusion criteria.Following reading titles and abstracts,original articles,and articles closely related to HSC transplantation with reliable argument and evidence and general analysis were included.Articles of repetitive studies and poor quality were excluded.RESULTS AND CONCLUSION:The HSC can be divided into liver-derived stem cells and non-liver-derived stem cells.Liver-derived stem cells include hepatic oval cells,mature liver cells and small hepatocyte-like progenitor cell.Non-liver-derived stem cells were mainly derived from embryonic stem cells,bone marrow hematopoietic stem cells and pancreatic stem cells.Currently,the research for the treatment of liver disease by HSC is still in its early stages.There are many difficult issues to be studied and solved in the discovery,separation,purification,comprehensive identification,cultivation,directed differentiation as well as clinical trials.However,as a new source of seed cells,HSC can not only replace the damaged tissue but can stimulate the receptor in tissue regeneration.Hence,compared with the clinical liver transplantation and bio-artificial liver,there are very bright future for the treatment of liver diseases by transplating HSC.

Relationship of subclasses of serum HDL and Apo A-Ⅰ gene polymorphism in hyperlipidemia / 中国病理生理杂志

AIM: To investigate apolipoprotein A-Ⅰ gene (Apo A-Ⅰ) polymorphism and its relationship with serum HDL subclasses in patients with hyperlipidemia (HL). METHODS: Apo A-Ⅰ genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 118 patients with hyperlipidemia and 109 healthy subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: Both in HL group and the control group, G/G and C/C genotypes were the most frequent at -78 bp and +83 bp of Apo A-Ⅰ gene, respectively. The frequency of rare A allele at -78 bp in HL group was significantly higher than that in control group. In HL group, subjects with G/A mutation had higher serum levels of TG, Apo C-Ⅲ, pre ?_1-HDL and HDL_ 3a , and lower levels of HDL_ 2a and HDL_ 2b compared to the subjects with G/G genotype. CONCLUSION: The G/A transition in the -78 bp position of the Apo A-Ⅰ gene promoter in patients with hyperlipidemia is associated with HDL subclasses. There is a general shift toward smaller sized HDL, which, in turn, indicates that HDL maturation might be abnormal.

Relationship between HDL subclasses and TC/HDL-C, TG/HDL-C ratio / 中国病理生理杂志

2.2 in serum, the particle size of HDL shifted towards smaller sizes, which indicates that reverse cholesterol transport might be weakened and HDL maturation might be abnormal.