Objective To investigate the effects of electroacupuncture at Baihui(GV20)point and Dazhui(GV14)point on cognitive function and potential mechanisms in Alzheimer's disease(AD)mice.Methods Forty-eight male five-transgenic familial Alzheimer's disease(5xFAD)mice were divided into four groups:empty vector group,knockdown group,empty vector+electroacupuncture group,and knockdown+electroacupuncture group.The knockdown group received Rho-associated coiled-coil containing protein kinase 2(ROCK2)knockdown via adeno-associated virus(AAV)microinjection technology.Knockdown efficiency was verified by polymerase chain reaction(PCR),and gene expression levels were confirmed by Western Blot.After 4 weeks of viral expression and transfection,electroacupuncture intervention at Baihui and Dazhui acupoints was administered for 4 weeks.Cognitive function was assessed using behavioral tests.Pathological products,inflammatory markers[interleukin 6(IL-6),tumor necrosis factor α(TNF-α)],and changes in the PI3K/AKT signaling pathway were detected using immunofluorescence staining,enzyme-linked immunosorbent assay(ELISA),and Western Blot techniques.Results Compared with the empty vector group,the ROCK2 knockdown group showed significantly improved spatial and contextual memory(P＜0.05 or P＜0.01),reduced amyloid deposition and inflammatory indicators(P＜0.05 or P＜0.01),and increased expression levels of phosphorylated protein kinase B(P-AKT)and phosphorylated phosphatidylinositol-3-kinase(P-PI3K)(P＜0.01),while the knockdown+electroacupuncture group exhibited more pronounced effects than knockdown group(P＜0.05 orP＜0.01).Conclusion Electroacupuncture at Baihui point and Dazhui point can regulate ROCK2 to activate the PI3K/AKT signaling pathway,improve cognitive impairment in AD mice,reduce Aβ deposition,and alleviate inflammatory responses.

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.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.