Mechanism of Qizhu Kang'ai Prescription for Inhibiting Proliferation of Hepatocellular Carcinoma by Regulating Tumor Metabolic Reprogramming via PCK1/Akt/p21 Signal Axis / 中国实验方剂学杂志

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl4） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G0/G1 phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G0/G1 phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Survey and strategies on the job stressors and burnout of senior nurses / 中国实用护理杂志

Objective To investigate the job stressors and burnout of senior nurses, and explore the possible strategies for alleviating stress and reduction of demission rate of senior nurses. Methods Two hundred and thirty head nurses and senior nurses were included in this study. Nurse Job Stressors Inventory (NJSI) and Maslach Burnout Inventory (MBI) were applied to evaluate the burnout and work-related stress of nurses with the combination of convenience sampling and cluster sampling. Results The NJSI scores of senior nurses and head nurses were (2.62 ± 0.56) points, (2.45 ± 0.47) points, the two scores were significantly different (t=-2.465,P<0.05); the scores of three dimensions of MBI in senior nurses were (30.01±11.86) points, (8.01±5.74) points, (35.35±9.57) points, while the scores in head nurses were (21.65±10.39) points, (5.14±3.37) points, (38.81±8.45) points. Statistically significant difference was seen between the two groups (t=-5.261,-4.705, 2.691,P<0.05). There was a higher positive correlation between job stressors and burnout of senior nurses (r=0.521) than head nurses (r=0.432). Conclusions The level of job burnout is higher in senior nurses than head nurses, attributing to the higher controllability of head nurses. It is suggested to reduce the job burnout of senior nurses and to keep senior nurses in the profession fields, based on the theory of magnetic hospital.

Effects of Sheng Mai San on the level of cell factors induced by lipopolysaccharide in chronic liver failure rats / 中国医师杂志

Objective To study the Sheng Mai San on the levels of cell factors induced by lipopolysaccharide in acute liver failure rats. Methods The models of chronic liver failure were constructed by injecting CCl4 in the abdomen of rats. The serum levels of lipopolysaccharide and cell factors were determined after treating with LPS and Sheng Mai San for 2 hours. Results The serum level of IL-6［(64.50±18.79)pg/ml vs (4.79±0.57)pg/ml］, ICAM-1［(25100.00±5258.85)pg/ml vs (4215.50±942.79)pg/ml］ and TNF-α［(17.55±2.39)pg/ml vs (10.92±5.02)pg/ml］ was increased by CCl4 (P＜0.05), but there is no effect on the serum level of LPS in rats ［(0.058±0.007)EU/ml vs (0.040±0.002)EU/ml,P＞0.05］. Sheng Mai San can significantly reduce the serum level of IL-6, ICAM-1 and TNF-α in rats with acute liver failure induced by CCl4 ［(17.20±3.12)pg/ml,(9490.00±2725.78)pg/ml,(3.00±1.00)pg/ml,P＜0.05］. After treating with LPS for 2 hours, the serum level of LPS, TNF-α, IL-6, ICAM-1 markedly increased ［(0.501±0.019)EU/ml,(19750.00±9655.17)pg/ml,(5615.00±490.50)pg/ml,(41000.00±589.88)pg/ml,P＜0.01］. Sheng Mai San could reduce the serum levels of LPS, TNF-α, IL-6, ICAM-1 and in rats with chronic liver failure (P＜0.01). Conclusions SD Rats in the state of chronic liver fail-ure, existing serious serum endotoxin, can induce the levels of cell factors by diversification inflammation reaction and. ShengMaiSan can regulating the levels of cell factors in rats with chronic liver failure.