Objective To investigate the effect of sufentanil(SUF)on interleukin-1β(IL-1β)-induced chondrocyte damage and its regulatory relationship on the Janus activated kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods Rat chondrocytes were randomly separated into control group(NC group),IL-1β group,SUF low concentration(SUF-L)+IL-1β group(SUF-L+IL-1β group),SUF high concentration(SUF-H)+IL-1β group(SUF-H+IL-1β group),and SUF-H+IL-1β+STAT3 activator Colivelin group(SUF-H+IL-1β+Colivelin group).CCK-8 method and clonal formation assay were applied to detect the proliferation of chondrocytes,while flow cytometry was used to detect the apoptosis;qRT-PCR method was applied to detect the relative mRNA expression levels of JAK2 and STAT3;Western blot was used to detect the expression level of JAK2/STAT3 signaling pathway related proteins;ELISA was applied to determine the expression levels of IFN-γ,IL-6 and IL-8 in cell culture media of each group.Results Compared with the NC group,the cell survival rate and the clones formation number of the IL-1β group decreased,while the apoptosis rate,relative expression levels of JAK2 and STAT3 mRNA,the values of p-JAK2/JAK2 and p-STAT3/STAT3,and the expression levels of IFN-γ,IL-6 and IL-8 in the cell culture medium all increased(P<0.05);compared with the IL-1β group,the changes in corresponding indicators of chondrocytes in the SUF-L+IL-1β group and SUF-H+IL-1β group were opposite to the above(P<0.05);Colivelin reversed the protective effects of high-dose SUF on IL-1β-induced chondrocyte damage(P<0.05).Conclusion SUF can protect chondrocytes from IL-1β-induced damage by down-regulating the JAK2/STAT3 signaling pathway.

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.

Objective To investigate the effect of sufentanil(SUF)on interleukin-1β(IL-1β)-induced chondrocyte damage and its regulatory relationship on the Janus activated kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods Rat chondrocytes were randomly separated into control group(NC group),IL-1β group,SUF low concentration(SUF-L)+IL-1β group(SUF-L+IL-1β group),SUF high concentration(SUF-H)+IL-1β group(SUF-H+IL-1β group),and SUF-H+IL-1β+STAT3 activator Colivelin group(SUF-H+IL-1β+Colivelin group).CCK-8 method and clonal formation assay were applied to detect the proliferation of chondrocytes,while flow cytometry was used to detect the apoptosis;qRT-PCR method was applied to detect the relative mRNA expression levels of JAK2 and STAT3;Western blot was used to detect the expression level of JAK2/STAT3 signaling pathway related proteins;ELISA was applied to determine the expression levels of IFN-γ,IL-6 and IL-8 in cell culture media of each group.Results Compared with the NC group,the cell survival rate and the clones formation number of the IL-1β group decreased,while the apoptosis rate,relative expression levels of JAK2 and STAT3 mRNA,the values of p-JAK2/JAK2 and p-STAT3/STAT3,and the expression levels of IFN-γ,IL-6 and IL-8 in the cell culture medium all increased(P<0.05);compared with the IL-1β group,the changes in corresponding indicators of chondrocytes in the SUF-L+IL-1β group and SUF-H+IL-1β group were opposite to the above(P<0.05);Colivelin reversed the protective effects of high-dose SUF on IL-1β-induced chondrocyte damage(P<0.05).Conclusion SUF can protect chondrocytes from IL-1β-induced damage by down-regulating the JAK2/STAT3 signaling pathway.

Objective: To investigate the prevalence and influencing factors of comorbidity of chronic diseases among hypertensive patients with uncontrolled blood pressure in Huzhou City, so as to provide insights into community hypertension control. Methods: Hypertensive patients with uncontrolled blood pressure at ages of 35 to 74 years were sampled using a cluster random sampling method from 5 districts (counties) of Huzhou City. Participants' demographics, living behaviors, and development of chronic diseases were collected using questionnaires, and the height, body weight, waist circumference and blood pressure were measured. Blood glucose, blood lipid and other biochemical parameters were detected, and the number and combination of comorbidity of chronic diseases were descriptively analyzed. Factors affecting the comorbidity of chronic diseases were identified using a multivariable ordinal logistic regression model. Results: A total of 1 215 respondents were included, with a mean age of (60.83±7.76) years, and including 652 men (53.66%) and 563 women (46.34%). The prevalence of dyslipidemia, diabetes, hyperuricemia and cardiac encephalopathy was 45.10%, 30.95%, 23.05% and 5.10%, respectively. The prevalence of comorbidity of chronic diseases was 69.22% among respondents, and there were 497 respondents with one comorbidity (40.91%), 272 with two comorbidities (22.39%) and 72 with three and more comorbidities (5.93%). Hypertension+dyslipidemia (20.74%), hypertension+diabetes+dyslipidemia (9.96%) and hypertension+diabetes+dyslipidemia+hyperuricemia (4.36%) were predominant comorbid combinations. Multivariable ordinal logistic regression analysis showed that participants with overweight (OR=1.782, 95%CI: 1.390-2.286), obesity (OR=2.411, 95%CI: 1.802-3.222), grade 2 hypertension (OR=1.438, 95%CI: 1.077-1.919) had a higher risk of multiple comorbidities than those with normal body mass index and controlled blood pressure, and women (OR=0.563, 95%CI: 0.456-0.696) had a lower risk of multiple comorbidities than men. Conclusions The prevalence of comorbidity of chronic diseases was 69.22% among community hypertensive patients with uncontrolled blood pressure in Huzhou City, and the comorbidity of chronic diseases mainly included dyslipidemia and diabetes. Men, overweight, obesity and hypertension resulted in a high risk of comorbidity of chronic diseases.

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