Objective To systematically evaluate the risk factors for postoperative delirium (POD) in patients undergoing pneumonectomy. Methods PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases were searched from the inception to November 7, 2024 for cross-sectional studies, case-control studies, and cohort studies on POD in patients undergoing pneumonectomy. Two researchers independently screened the literature, extracted data, and evaluated the quality of the literature. RevMan 5.4.1 software was used for meta-analysis. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature. Results A total of 12 studies were included, with 5 574 patients. The NOS scores of the literature were all≥6 points. Meta-analysis results showed that age (≥60 years) [OR=2.43, 95%CI (2.01, 2.93), P<0.01], American Society of Anesthesiologists (ASA) classification (Ⅳ) [OR=8.74, 95%CI (5.23, 14.61), P<0.01], history of diabetes [OR=12.81, 95%CI (10.45, 15.71), P<0.01], history of cerebrovascular disease [OR=3.00, 95%CI (2.46, 3.67), P<0.01], depression [OR=7.27, 95%CI (5.46, 9.67), P<0.01], squamous cell carcinoma [OR=4.79, 95%CI (1.83, 12.51), P<0.01], malnutrition [OR=5.25, 95%CI (3.35, 8.25), P<0.01], sleep disorders [OR=2.79, 95%CI (2.28, 3.42), P<0.01], and duration of one-lung ventilation during surgery [OR=1.32, 95%CI (1.11, 1.57), P<0.01] were all risk factors for POD, while high body mass index (BMI) [OR=0.96, 95%CI (0.95, 0.97), P<0.01] was a protective factor for POD. Conclusion Age (≥60 years), ASA classification (Ⅳ), history of diabetes, history of cerebrovascular disease, depression, squamous cell carcinoma, malnutrition, sleep disorders, and duration of one-lung ventilation during surgery are independent risk factors for POD, while high BMI is a protective factor.

ObjectiveTo investigate the effects of three-dimensional foot-ankle exercises (3DFAE) on mild-to-moderate hallux valgus in young women. MethodsFrom October to December, 2024, 45 female patients aged 18 to 26 years with hallux valgus were recruited from Capital University of Physical Education and Sports. They were randomly divided into control group (n = 15), toe-spread-out (TSO) group (n = 15) and 3DFAE group (n = 15). The control group only received foot health education, while the two intervention groups performed corresponding exercise training, for four weeks. Hallux valgus angle (HVA) was measured with photographic method, abductor hallucis activation was detected with surface electromyography, cross-sectional area of abductor hallucis was measured with Doppler ultrasound, and active ankle dorsiflexion range of motion (ROM) was assessed with a goniometer, before intervention, immediately after intervention, and four weeks after training cessation. A perceived difficulty scale was adopted to evaluate the training difficulty of TSO group and 3DFAE group at the first training session and upon completion of intervention. ResultsThe effects of time and interaction were significant for bilateral HVA, abductor hallucis activation, cross-sectional area of abductor hallucis and ankle dorsiflexion ROM (F > 2.728, P < 0.05), and the effect of group of left ankle dorsiflexion ROM was also significant (F = 4.995, P < 0.05). After intervention, bilateral HVA, abductor hallucis activation, cross-sectional area of abductor hallucis and ankle dorsiflexion ROM were all better than those before intervention (P < 0.05), and most indicators were superior to those measured at the 4-week follow-up (P < 0.05). The left ankle dorsiflexion ROM was better in 3DFAE group than in the control group and TSO group (P < 0.05). At the first intervention session, the perceived training difficulty was lower in 3DFAE group than in TSO group (t = 3.334, P = 0.002), and it decreased (t = 5.292, P < 0.001) after four weeks of training in TSO group, with no significant difference compared with 3DFAE group (P > 0.05). Conclusion3DFAE can improve ankle dorsiflexion ROM in young female patients with hallux valgus, with no more difficulty than TSO, and lower initial operation difficulty.

BACKGROUND:Ossification of the ligamentum flavum was previously considered to be rare in the population.As research has progressed,its incidence rate is increasing gradually,which has aroused the interest of a large number of researchers. OBJECTIVE:To visualize and analyze the research results on ossification of the ligamentum flavum from the Web of Science Core Collection since 1999 using bibliometric methods,and to review the research history of ossification of the ligamentum flavum,highlighting important literature,summarizing research hotspots,and providing ideas for researchers to find research directions. METHODS:Using the Web of Science Core Collection as the data source,relevant papers on ossification of the ligamentum flavum were searched and screened.VOSviewer 1.6.19 and CiteSpace 6.2.R6 were used to conduct the visual analysis of annual publication volume,research countries,institutions,citations,journals,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 347 papers were included.Since 1999,the number of published papers has increased in a spiral pattern.China's research started later than Japan's,but the number of publications has come up later,with Peking University being the institution with the most publications,and Prof.Chen Zhongqiang from Peking University being the scholar with the most publications.(2)Five of the 10 most frequently cited publications were related to the surgical treatment of the disease.(3)Excluding keywords directly related to the research topic and synthetically analyzing frequencies and betweenness centralities of key words,terms such as"thoracic myelopathy,""dural ossification,""minimally invasive surgery,"and"ossification of the posterior longitudinal ligament"occupied a central position in this field.(4)Keywords clustering analysis showed that clinical manifestations and surgical treatment of ossification of the ligamentum flavum accounted for a large proportion of study.(5)The timeline and burst analysis of keywords revealed that"minimally invasive surgery"appeared as a keyword around 2015,with the highest burst strength and the latest burst start time,and began to receive extensive attention from researchers in 2019.The burst of the keyword"dural ossification"has not yet ended.(6)Surgical treatment for ossification of the ligamentum flavum has been at the forefront of research.Development and research of minimally invasive surgery and research on dural ossification secondary to ossification of the ligamentum flavum are both current research hotspots and possible future research trends.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

Objective To investigate the application value of spectral CT multi-quantitative parameters combined with clinical characteristics in predicting high-risk gastroesophageal varices(GOV)in patients with liver cirrhosis.Methods The results of upper abdominal spectral CT enhancement and electronic gastroscopy in 112 patients diagnosed with liver cirrhosis were analyzed retrospec-tively,and the clinical data were collected.According to the gastroscopic manifestations,the patients were divided into high-risk GOV group(n=74)and low-risk GOV group(n=38).Univariate analysis was used to compare the spectral CT quantitative parameters and clinical characteristics between the two groups.Multivariate logistic regression analysis was used to screen the independent risk factors for high-risk GOV.R software was used to construct a nomogram model for predicting high-risk GOV,and the differentia-tion,calibration and clinical practicability of the prediction model were evaluated.Results The normalized iodine concentration(NIC)of liver left lobe,prothrombin time(PT),albumin(ALB)and liver function grading were independent risk factors for high-risk GOV(P＜0.05).The area under the curve(AUC)of receiver operating characteristic(ROC)curve of predicting high-risk GOV in nomo-gram model was 0.893.Calibration curve showed that the predicted results were basically consistent with the actual results.Decision curve analysis(DCA)showed that the prediction model had good clinical practicability.Conclusion The nomogram model based on NIC of liver left lobe,PT,ALB and liver function grading is helpful to predict patients with high-risk GOV in liver cirrhosis,and pro-vides a reference for clinical prevention and treatment of esophagogastric variceal bleeding(EVB).

Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.