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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.
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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.
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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.
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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.