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Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P＜0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P＜0.05).However,no significant changes were observed in absolute liver weight(P＞0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P＜0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P＜0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.

Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P＜0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P＜0.05).However,no significant changes were observed in absolute liver weight(P＞0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P＜0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P＜0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.

Protein polypeptides are a class of bioactive substances that play a crucial role in maintaining the stability of various functions of the organism.Rapid and accurate detection of their levels could help in the diagnosis of diseases,the monitoring of drug therapy and the research and development of medicines,which is of great significance in the fields of clinical medicine,biology and pharmacy.Conventional protein polypeptides detection methods,such as Western blotting and enzyme-linked immunosorbent assay,still have problems like low sensitivity or difficulty in determining more than 1 analyte simultaneously.Liquid chromatography-mass spectrometry(LC-MS)has the advantages of specificity,sensitivity and high throughput.However,low ionization efficiency of macromolecules and strong biological matrix effects limit the feasibility of direct detection of protein polypeptides by LC-MS,which has led to the development of signal conversion and amplification strategies based on LC-MS technology.In this review,we summarized the research progress of sample pretreatment methods and signal conversion and amplification strategies for quantification of protein polypeptides in vivo based on LC-MS in recent years,providing a reference for developing specific high-sensitivity detection methods for low-abundance protein polypeptides in complex samples based on LC-MS technology.

Myocarditis has diverse clinical manifestations,which might develop into acute heart failure,cardiogenic shock and chronic dilated cardiomyopathy.Early diagnosis of myocarditis is crucial for improving prognosis.Cardiac MRI(CMRI)can display myocardial necrosis,fibrosis and edema,having become the best imaging method for evaluating myocarditis.The progresses in multi-parameter CMRI researches of acute myocarditis were reviewed in this article.

Purpose: This study investigated whether professional identity predicts learning burnout among Chinese nursing students, and whether resilience moderates this relationship. Methods: This cross-sectional study recruited 635 students from a nursing college at a medical university in Hefei, China. Data were collected using the professional identity questionnaire, learning burnout scale for college students, and 10-item Connor-Davidson Resilience Scale. Pearson’s correlation analysis was used to investigate the relationships between variables. The mediation effect was evaluated using linear regression and the bootstrap method in SPSS. Results: Nursing students exhibited intermediate learning burnout levels (score: 54.95 ± 10.42). Professional identity was positively correlated with psychological resilience (r = .42, p < .001), whereas learning burnout was negatively correlated with professional identity (r = - .54, p < .001) and psychological resilience (r = -.57, p < .001). Psychological resilience mediated the relationship between professional identity and learning burntout to the tune of 32.8%. Conclusion Psychological resilience mediates the relationship between professional identity and learning burnout. Thus, nursing educators can mitigate student burnout by developing their students' professional identities and psychological resilience.

Purpose: This study investigated whether professional identity predicts learning burnout among Chinese nursing students, and whether resilience moderates this relationship. Methods: This cross-sectional study recruited 635 students from a nursing college at a medical university in Hefei, China. Data were collected using the professional identity questionnaire, learning burnout scale for college students, and 10-item Connor-Davidson Resilience Scale. Pearson’s correlation analysis was used to investigate the relationships between variables. The mediation effect was evaluated using linear regression and the bootstrap method in SPSS. Results: Nursing students exhibited intermediate learning burnout levels (score: 54.95 ± 10.42). Professional identity was positively correlated with psychological resilience (r = .42, p < .001), whereas learning burnout was negatively correlated with professional identity (r = - .54, p < .001) and psychological resilience (r = -.57, p < .001). Psychological resilience mediated the relationship between professional identity and learning burntout to the tune of 32.8%. Conclusion Psychological resilience mediates the relationship between professional identity and learning burnout. Thus, nursing educators can mitigate student burnout by developing their students' professional identities and psychological resilience.

Purpose: This study investigated whether professional identity predicts learning burnout among Chinese nursing students, and whether resilience moderates this relationship. Methods: This cross-sectional study recruited 635 students from a nursing college at a medical university in Hefei, China. Data were collected using the professional identity questionnaire, learning burnout scale for college students, and 10-item Connor-Davidson Resilience Scale. Pearson’s correlation analysis was used to investigate the relationships between variables. The mediation effect was evaluated using linear regression and the bootstrap method in SPSS. Results: Nursing students exhibited intermediate learning burnout levels (score: 54.95 ± 10.42). Professional identity was positively correlated with psychological resilience (r = .42, p < .001), whereas learning burnout was negatively correlated with professional identity (r = - .54, p < .001) and psychological resilience (r = -.57, p < .001). Psychological resilience mediated the relationship between professional identity and learning burntout to the tune of 32.8%. Conclusion Psychological resilience mediates the relationship between professional identity and learning burnout. Thus, nursing educators can mitigate student burnout by developing their students' professional identities and psychological resilience.

Purpose: This study investigated whether professional identity predicts learning burnout among Chinese nursing students, and whether resilience moderates this relationship. Methods: This cross-sectional study recruited 635 students from a nursing college at a medical university in Hefei, China. Data were collected using the professional identity questionnaire, learning burnout scale for college students, and 10-item Connor-Davidson Resilience Scale. Pearson’s correlation analysis was used to investigate the relationships between variables. The mediation effect was evaluated using linear regression and the bootstrap method in SPSS. Results: Nursing students exhibited intermediate learning burnout levels (score: 54.95 ± 10.42). Professional identity was positively correlated with psychological resilience (r = .42, p < .001), whereas learning burnout was negatively correlated with professional identity (r = - .54, p < .001) and psychological resilience (r = -.57, p < .001). Psychological resilience mediated the relationship between professional identity and learning burntout to the tune of 32.8%. Conclusion Psychological resilience mediates the relationship between professional identity and learning burnout. Thus, nursing educators can mitigate student burnout by developing their students' professional identities and psychological resilience.