Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective:To analyze the epidemic trend of influenza-like illness（ILI）cases，etiological detection results，and the evolution of the hemagglutinin（HA）gene of the predominant strains in Hanzhong City，Shaanxi Province during the 2018-2024 influenza seasons.Methods:ILI sentinel surveillance data and network laboratory test results during the 2018-2024 influenza seasons in Hanzhong City，Shaanxi Province were collected for descriptive analysis. The HA gene sequences of 25 predominant strains were obtained through whole-genome deep sequencing method，and then compared with the vaccine strains recommended by the World Health Organization in the same period to analyze the evolution of the virus.Results:A total of 37 770 cases of ILI were reported in Hanzhong City during the 2018-2024 influenza seasons，and the proportion of total ILI cases（ILI%）was 2.87%（37 770/1 316 009）. The epidemic trend of ILI showed an obvious epidemic peak in winter and spring（from December of the current year to March of the following year）. The specimens with the highest positive rate were of type A（H3N2）（39.12%，365/933），and the predominant epidemic strains in each influenza season alternated among A（H1N1）pdm09（in the 2018-2019 and 2022-2023 influenza seasons），A（H3N2）（in the 2019-2020 and 2023-2024 influenza seasons）and B（Victoria）（in the 2021-2022 influenza season）. The phylogenetic relationship gradually became more distant over time across different influenza seasons. Among them，the epidemic strains of A（H1N1）pdm09 belonged to the 6B.1 clade，and the evolution mainly occurred in the Sa and Sb regions of the HA epitope. Meanwhile，the epidemic strains of A（H3N2）belonged to the 3C clade，and the evolution mainly took place in the A，B and C regions of the HA epitope. The strains of the B（Victoria）lineage belonged to the V1a.3a.2 clade，and the evolution mainly occurred in the 120-loop，150-loop，and 190-helix regions of the HA epitope.Conclusions:The influenza epidemic in Hanzhong City has obvious seasonality，and the amino acids of the epidemic strains have shown a certain degree of variation over the years. In future prevention and control work，influenza surveillance should be continuously strengthened，and the change trend of the predominant circulating strains should be closely monitored.

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Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective:To investigate the risk factors of post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke, to establish a nomogram predictive model to help clinicians predict and intervene in the people who are prone to PSCI in advance, and to improve the recognition, intervention and prevention of the disease at an early stage, so as to provide a new way of thinking for the diagnosis and treatment of PSCI.Methods:Totally 330 patients with acute ischemic stroke hospitalized in the Department of Neurology, the First Bethune Hospital of Jilin University from January 2021 to June 2023 were collected. Their general clinical data, laboratory examination, imaging examination, and neuropsychological assessment data were collected. Neuropsychological scales assessment was completed within 7 days of the onset of acute ischemic stroke as a baseline value. The patients were followed up with neuropsychological scales assessment 6 months after the onset of stroke, and according to the results of the Montreal Cognitive Assessment (MoCA) scale assessment 6 months later, the patients were divided into PSCI group (143 patients) and post-stroke non-cognitive impairment (PSNCI) group (147 patients) (40 patients were removed from the study after 6 months, and a total of 290 patients were finally included in the study). Comparisons of general clinical information between the PSCI and PSNCI groups were first performed using statistical methods; then more influential predictors were selected using least absolute shrinkage and selection operator (LASSO) regression method and included in multifactor Logistic regression analyses to create a nomogram predictive model. Internal validation was performed by repeating the sampling 1 000 times using the bootstrap method; receiver operating characteristic (ROC) curve and area under the curve (AUC) were plotted to analyze the discrimination of the predictive model; the accuracy of the model was assessed using calibration curves; and a decision curve analysis (DCA) diagram was plotted to assess the clinical utility of the model.Results:Age, education level, critical area cerebral infarction, low-density lipoprotein-cholesterol (LDL-C), cerebral white matter hyperintensity (WMH), and cerebral atrophy were selected as the predictors of the nomogram predictive model by LASSO regression, and the results of multifactor Logistic regression analysis showed that these predictors were independent risk factors for PSCI in patients with acute ischemic stroke; the risk predictive model established was validated, and the results showed that the AUC of the present predictive model was 0.890, and the AUC of the internally validated predictive model was 0.940, suggesting that the model had a good degree of differentiation; the good fit between the calibration curve and the actual prediction results indicated that the model had good accuracy; the DCA results showed that the model can be well applied in clinical practice.Conclusion:The nomogram predictive model consisting of age, education level, critical area cerebral infarction, LDL-C, WMH, and cerebral atrophy has good differentiation, accuracy, and clinical utility, and can be used in practical clinical practice, which can help clinicians screen patients who are prone to PSCI, and intervene in a timely manner to achieve better clinical outcomes.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective:To analyze the epidemic trend of influenza-like illness（ILI）cases，etiological detection results，and the evolution of the hemagglutinin（HA）gene of the predominant strains in Hanzhong City，Shaanxi Province during the 2018-2024 influenza seasons.Methods:ILI sentinel surveillance data and network laboratory test results during the 2018-2024 influenza seasons in Hanzhong City，Shaanxi Province were collected for descriptive analysis. The HA gene sequences of 25 predominant strains were obtained through whole-genome deep sequencing method，and then compared with the vaccine strains recommended by the World Health Organization in the same period to analyze the evolution of the virus.Results:A total of 37 770 cases of ILI were reported in Hanzhong City during the 2018-2024 influenza seasons，and the proportion of total ILI cases（ILI%）was 2.87%（37 770/1 316 009）. The epidemic trend of ILI showed an obvious epidemic peak in winter and spring（from December of the current year to March of the following year）. The specimens with the highest positive rate were of type A（H3N2）（39.12%，365/933），and the predominant epidemic strains in each influenza season alternated among A（H1N1）pdm09（in the 2018-2019 and 2022-2023 influenza seasons），A（H3N2）（in the 2019-2020 and 2023-2024 influenza seasons）and B（Victoria）（in the 2021-2022 influenza season）. The phylogenetic relationship gradually became more distant over time across different influenza seasons. Among them，the epidemic strains of A（H1N1）pdm09 belonged to the 6B.1 clade，and the evolution mainly occurred in the Sa and Sb regions of the HA epitope. Meanwhile，the epidemic strains of A（H3N2）belonged to the 3C clade，and the evolution mainly took place in the A，B and C regions of the HA epitope. The strains of the B（Victoria）lineage belonged to the V1a.3a.2 clade，and the evolution mainly occurred in the 120-loop，150-loop，and 190-helix regions of the HA epitope.Conclusions:The influenza epidemic in Hanzhong City has obvious seasonality，and the amino acids of the epidemic strains have shown a certain degree of variation over the years. In future prevention and control work，influenza surveillance should be continuously strengthened，and the change trend of the predominant circulating strains should be closely monitored.

Objective:To investigate the risk factors of post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke, to establish a nomogram predictive model to help clinicians predict and intervene in the people who are prone to PSCI in advance, and to improve the recognition, intervention and prevention of the disease at an early stage, so as to provide a new way of thinking for the diagnosis and treatment of PSCI.Methods:Totally 330 patients with acute ischemic stroke hospitalized in the Department of Neurology, the First Bethune Hospital of Jilin University from January 2021 to June 2023 were collected. Their general clinical data, laboratory examination, imaging examination, and neuropsychological assessment data were collected. Neuropsychological scales assessment was completed within 7 days of the onset of acute ischemic stroke as a baseline value. The patients were followed up with neuropsychological scales assessment 6 months after the onset of stroke, and according to the results of the Montreal Cognitive Assessment (MoCA) scale assessment 6 months later, the patients were divided into PSCI group (143 patients) and post-stroke non-cognitive impairment (PSNCI) group (147 patients) (40 patients were removed from the study after 6 months, and a total of 290 patients were finally included in the study). Comparisons of general clinical information between the PSCI and PSNCI groups were first performed using statistical methods; then more influential predictors were selected using least absolute shrinkage and selection operator (LASSO) regression method and included in multifactor Logistic regression analyses to create a nomogram predictive model. Internal validation was performed by repeating the sampling 1 000 times using the bootstrap method; receiver operating characteristic (ROC) curve and area under the curve (AUC) were plotted to analyze the discrimination of the predictive model; the accuracy of the model was assessed using calibration curves; and a decision curve analysis (DCA) diagram was plotted to assess the clinical utility of the model.Results:Age, education level, critical area cerebral infarction, low-density lipoprotein-cholesterol (LDL-C), cerebral white matter hyperintensity (WMH), and cerebral atrophy were selected as the predictors of the nomogram predictive model by LASSO regression, and the results of multifactor Logistic regression analysis showed that these predictors were independent risk factors for PSCI in patients with acute ischemic stroke; the risk predictive model established was validated, and the results showed that the AUC of the present predictive model was 0.890, and the AUC of the internally validated predictive model was 0.940, suggesting that the model had a good degree of differentiation; the good fit between the calibration curve and the actual prediction results indicated that the model had good accuracy; the DCA results showed that the model can be well applied in clinical practice.Conclusion:The nomogram predictive model consisting of age, education level, critical area cerebral infarction, LDL-C, WMH, and cerebral atrophy has good differentiation, accuracy, and clinical utility, and can be used in practical clinical practice, which can help clinicians screen patients who are prone to PSCI, and intervene in a timely manner to achieve better clinical outcomes.

Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P＜0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P＜0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P＜0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P＜0.05).There was no significant difference between Fer-1 group and con-trol group(P＜0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P＜0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.

BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.