Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Objective To observe the effects of acupuncture at"Jiaji"on angiogenesis in rats with lumbar muscle aging based on AMPK/SIRT1/PGC-1α signaling pathway;To explore its possible mechanism of improving lumbar muscle aging atrophy.Methods Totally 30 SPF male SD rats were randomly divided into model group,acupuncture group and non-acupoint group,with 10 rats in each group.Subcutaneous injection of D-galactose(300 mg/kg)into the neck and back of rats was used to prepare a subacute lumbar muscle aging rat model.Another 10 rats were selected as the blank group,and an equal amount of normal saline was subcutaneously injected into the neck and back.Intervention began in the 9th week of modeling.The acupuncture group received acupuncture at bilateral L3-L5"Jiaji",while the non-acupoint group received bilateral non-meridian and non-acupoint acupuncture,each time for 30 minutes,once a day,6 times a week,for 4 consecutive weeks.β-galactosidase staining was used to observe the morphology of rat lumbar muscle tissue;TUNEL staining was used to detect apoptosis of lumbar muscle tissue cells;ELISA was used to detect the contents of nitric oxide(NO)and endothelin-1(ET-1)in lumbar muscle tissue;immunofluorescence staining was used to detect CD31 expression and microvascular density in lumbar muscle tissue;Western blot was used to detect protein expressions of p-AMP activated protein kinase(AMPK),silencing information regulatory factor 1(SIRT1)and peroxisome proliferator activated receptor gamma co activator factor 1α(PGC-1α)in lumbar muscle tissue.Results Compared with the blank group,the positive cells of β-galactosidase staining in lumbar muscle tissue of the model group increased significantly,the apoptosis rate significantly increased(P<0.001),the NO content in lumbar muscle tissue significantly decreased(P<0.001),the ET-1 content significantly increased(P<0.001),the expression of CD31 and microvascular density significantly decreased(P<0.001),and the protein expressions of p-AMPK,SIRT1 and PGC-1α significantly decreased(P<0.01,P<0.001).Compared with the model group,the positive cells of β-galactosidase staining in lumbar muscle tissue of rats in the acupuncture group was significantly reduced,the apoptosis rate was significantly decreased(P<0.001),NO content significantly increased(P<0.001),ET-1 content was significantly reduced(P<0.01),CD31 expression and microvascular density significantly increased(P<0.01,P<0.001),and the protein expressions of p-AMPK,SIRT1,PGC-1α significantly increased(P<0.05,P<0.01).Conclusion Acupuncture at"Jiaji"can promote angiogenesis in lumbar skeletal muscle,and then improve the aging atrophy of lumbar muscle,and its mechanism may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway.

Objective:To identify the key differentially expressed gene, BTF3, in cutaneous squamous cell carcinoma(cSCC)using bioinformatics methods and to preliminarily explore the potential mechanisms of BTF3 and its co-expressed genes in cSCC development. Methods:The cSCC-related datasets(GSE98767, GSE42677, GSE45164)were obtained from the Gene Expression Omnibus(GEO)database.Differential expression analysis revealed BTF3 as a significantly differentially expressed gene in cSCC.A BTF3-related co-expressed gene network was constructed and subjected to gene ontology(GO)enrichment analysis to investigate the biological processes, molecular functions, and cellular components that were significantly enriched.The study selected 60 paraffin-embedded tissue samples from the First Affiliated Hospital of Jinzhou Medical University, collected between 2020 and 2024.This cohort included 30 samples from cSCC patients and 30 samples from patients who underwent excision of melanocytic nevi.Immunohistochemical experiments were conducted to assess the expression of BTF3 in cSCC tissues.Additionally, single-sample gene set enrichment analysis(ssGSEA)was performed to assess the relevance of BTF3 to immune cells, and protein-protein interaction(PPI)analysis was employed to identify critical gene networks. Results:BTF3 was significantly overexpressed in cSCC, as confirmed by immunohistochemistry.The receiver operating characteristic(ROC)curve indicated that BTF3 exhibited moderate classification accuracy.Co-expression analysis revealed that positively correlated genes with BTF3 included EIF3E and HSPA14, while negatively correlated genes included SZRD1 and ARHGEF2.GO analysis demonstrated that BTF3 was enriched in biological processes such as glucose metabolism, signaling in response to deoxyribonucleic acid (DNA)damage, endogenous apoptotic signaling pathways, platelet morphogenesis, and platelet formation.Additionally, ssGSEA indicated a significant association of BTF3 with memory B cells and a notable correlation with low CD56-expressing natural killer cells. Conclusions:BTF3 is significantly overexpressed in cSCC and may represent a promising diagnostic and therapeutic target by influencing key gene networks and modulating the immune microenvironment.

Objective To investigate the expression level and diagnostic value of serum cysteine protease inhibitor S(CST4)in patients with gastric cancer.Methods Clinical data of 115 patients with suspected gastric cancer who complained of gastric discomfort were retrospectively analyzed,and they were divided into benign disease group(n=50),precancerous disease group(n=26)and gas-tric cancer group(n=39).The levels of serum CST4,carcinoembryonic antigen(CEA),carbohy-drate antigen 19-9(CA19-9)and carbohydrate antigen 72-4(CA72-4)were analyzed in the three groups.The positive rates of CST4 among the three groups were compared.Binary Logistic regression analysis was used to screen for independent risk factors for gastric cancer occurrence.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of CST4 in gastric cancer.Results The positive rate of CST4 was 6.00％(3/50)in the benign gastric disease group,30.77％(8/26)in the gastric precancerous lesion group,and 66.67％(26/39)in the gastric canc-er group.The positive rate of CST4 in the gastric cancer group was higher than that in the gastric pre-cancerous lesion group and the benign gastric disease group(P＜0.05).The results of binary Logistic regression analysis showed that advanced age,high levels of serum CST4 and high levels of CEA were independent risk factors for gastric cancer occurrence(P＜0.05).The area under the curve(AUC)for CST4 alone in diagnosing gastric cancer was 0.847(95％CI,0.760 to 0.934),with an optimal cut-off value of 94.6 U/mL,the Youden index of 0.638,sensitivity of 71.8％,and specificity of 92.0％.The AUC for the combined diagnosis of gastric cancer using CST4,age and CEA was 0.959(95％CI,0.919 to 0.992),with sensitivity of 94.9％and specificity of 86.0％.Conclusion As a novel se-rum marker,CST4 has high predictive value in the auxiliary diagnosis of gastric cancer.

Objective To observe the effects of acupuncture at"Jiaji"on angiogenesis in rats with lumbar muscle aging based on AMPK/SIRT1/PGC-1α signaling pathway;To explore its possible mechanism of improving lumbar muscle aging atrophy.Methods Totally 30 SPF male SD rats were randomly divided into model group,acupuncture group and non-acupoint group,with 10 rats in each group.Subcutaneous injection of D-galactose(300 mg/kg)into the neck and back of rats was used to prepare a subacute lumbar muscle aging rat model.Another 10 rats were selected as the blank group,and an equal amount of normal saline was subcutaneously injected into the neck and back.Intervention began in the 9th week of modeling.The acupuncture group received acupuncture at bilateral L3-L5"Jiaji",while the non-acupoint group received bilateral non-meridian and non-acupoint acupuncture,each time for 30 minutes,once a day,6 times a week,for 4 consecutive weeks.β-galactosidase staining was used to observe the morphology of rat lumbar muscle tissue;TUNEL staining was used to detect apoptosis of lumbar muscle tissue cells;ELISA was used to detect the contents of nitric oxide(NO)and endothelin-1(ET-1)in lumbar muscle tissue;immunofluorescence staining was used to detect CD31 expression and microvascular density in lumbar muscle tissue;Western blot was used to detect protein expressions of p-AMP activated protein kinase(AMPK),silencing information regulatory factor 1(SIRT1)and peroxisome proliferator activated receptor gamma co activator factor 1α(PGC-1α)in lumbar muscle tissue.Results Compared with the blank group,the positive cells of β-galactosidase staining in lumbar muscle tissue of the model group increased significantly,the apoptosis rate significantly increased(P<0.001),the NO content in lumbar muscle tissue significantly decreased(P<0.001),the ET-1 content significantly increased(P<0.001),the expression of CD31 and microvascular density significantly decreased(P<0.001),and the protein expressions of p-AMPK,SIRT1 and PGC-1α significantly decreased(P<0.01,P<0.001).Compared with the model group,the positive cells of β-galactosidase staining in lumbar muscle tissue of rats in the acupuncture group was significantly reduced,the apoptosis rate was significantly decreased(P<0.001),NO content significantly increased(P<0.001),ET-1 content was significantly reduced(P<0.01),CD31 expression and microvascular density significantly increased(P<0.01,P<0.001),and the protein expressions of p-AMPK,SIRT1,PGC-1α significantly increased(P<0.05,P<0.01).Conclusion Acupuncture at"Jiaji"can promote angiogenesis in lumbar skeletal muscle,and then improve the aging atrophy of lumbar muscle,and its mechanism may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway.

Objective:To identify the key differentially expressed gene, BTF3, in cutaneous squamous cell carcinoma(cSCC)using bioinformatics methods and to preliminarily explore the potential mechanisms of BTF3 and its co-expressed genes in cSCC development. Methods:The cSCC-related datasets(GSE98767, GSE42677, GSE45164)were obtained from the Gene Expression Omnibus(GEO)database.Differential expression analysis revealed BTF3 as a significantly differentially expressed gene in cSCC.A BTF3-related co-expressed gene network was constructed and subjected to gene ontology(GO)enrichment analysis to investigate the biological processes, molecular functions, and cellular components that were significantly enriched.The study selected 60 paraffin-embedded tissue samples from the First Affiliated Hospital of Jinzhou Medical University, collected between 2020 and 2024.This cohort included 30 samples from cSCC patients and 30 samples from patients who underwent excision of melanocytic nevi.Immunohistochemical experiments were conducted to assess the expression of BTF3 in cSCC tissues.Additionally, single-sample gene set enrichment analysis(ssGSEA)was performed to assess the relevance of BTF3 to immune cells, and protein-protein interaction(PPI)analysis was employed to identify critical gene networks. Results:BTF3 was significantly overexpressed in cSCC, as confirmed by immunohistochemistry.The receiver operating characteristic(ROC)curve indicated that BTF3 exhibited moderate classification accuracy.Co-expression analysis revealed that positively correlated genes with BTF3 included EIF3E and HSPA14, while negatively correlated genes included SZRD1 and ARHGEF2.GO analysis demonstrated that BTF3 was enriched in biological processes such as glucose metabolism, signaling in response to deoxyribonucleic acid (DNA)damage, endogenous apoptotic signaling pathways, platelet morphogenesis, and platelet formation.Additionally, ssGSEA indicated a significant association of BTF3 with memory B cells and a notable correlation with low CD56-expressing natural killer cells. Conclusions:BTF3 is significantly overexpressed in cSCC and may represent a promising diagnostic and therapeutic target by influencing key gene networks and modulating the immune microenvironment.

Objective To explore the mechanism of malignant behavior of cervical cancer(CC)cells based on AMP-activated protein kinase(AMPK)/rapamycin target protein(mTOR)signaling pathway mediated by nucleo-tide-binding oligomerization domain receptor 2(NOD2).Methods Bioinformatics analysis was performed to deter-mine the expression of NOD2 in CC tissue.Plasmids targeting NOD2(shNOD2)and shRNAs negative control(shNC),NOD2 overexpression(NOD2)and vectors(Vec)were transfected into CC cells.The effect of NOD2 on the growth of CC cells was determined by cell counting kit-8 assay,colony formation and Transwell cell invasion as-say.Transcriptome analysis was performed by high throughput RNA sequencing(RNA-Seq).Western blot was used to detect the expression of NOD2,AMPK/mTOR signaling pathway and autophagy protein in the cell line.24 female BALB/c nude mice were randomly divided into four groups,with 6 mice in each group:vector group(Vec group),NOD2 overexpression group(NOD2 group),shNC group and shNOD2 group.The distant metastasis mod-el was established in mice,and the fluorescence intensity of lung metastasis was monitored and the number of lung metastasis nodules was counted.Results On-line database analysis showed that the expression of NOD2 in CC tis-sues was significantly higher than that in normal tissues,and there were significant differences in the mRNA expres-sion of NOD2 in different stages of CC(P＜0.05).In addition,the high expression of NOD2 was associated with poor overall survival and disease-free survival(P＜0.05).NOD2 overexpression promoted the proliferation,colony formation,migration and invasion of CC cells,while NOD2 knock-down was the opposite.Consistent with the re-sults in vitro,the lung colonization and lung metastasis of CC cells in NOD2 group were significantly higher than those in Vec group(P＜0.05),while those in shNOD2 group were significantly lower than those in shNC group(P＜0.05).RNA-Seq results showed that the expression of NOD2 was significantly related to AMPK signal activa-tion,mTOR signal inhibition,autophagy regulation pathway activation and autophagy formation.Compared with shNC group,the expression of phosphorylated AMPK and LC3 protein decreased significantly in shNOD2 group(P＜0.05),and the expression levels of phosphorylated mTOR and p62 protein increased significantly(P＜0.05).Compared with Vec group,the expression levels of LC3 and AMPK protein in NOD2 group increased significantly(P＜0.05),and the expression levels of phosphorylated mTOR and p62 protein decreased significantly(P＜0.05).Compared with shNC group,the point accumulation of GFP-mRFP-LC3 in shNOD2 group decreased signifi-cantly(P＜0.05).Compared with Vec group,the point accumulation of GFP-mRFP-LC3 increased significantly(P＜0.05).Conclusion NOD2 may promote the proliferation,migration and invasion of CC through AMPK/mTOR signal,and its mechanism partly involves autophagy activation.

Objective To evaluate the apparent diffusion coefficient(ADC)values of different bone marrow infiltration patterns in multiple myeloma(MM)patients with MR whole-body diffusion weighted imaging(WB-DWI)and to determine the ADC thresholds for different bone marrow infiltration patterns.Methods Nineteen MM patients diagnosed for the first time were selected.The lesions types of each site(cervical spine,ribs,sternum,humerus,scapula,sacral spine,ilium,femur,thoracic spine,and lumbar spine)after the WB-DWI images were visually evaluated,which were divided into focal group(including focal lesion in combined focal and diffuse infiltration)[region of interest(ROI)=141],pure diffuse infiltration group(ROI=150),diffuse lesion in combined focal and diffuse infiltration group(ROI=127),"salt-and-pepper"group(ROI=54),and normal appearance group(ROI=68).ADC values were measured and compared between each group and the receiver operating characteristic(ROC)curve was drawn to distinguish different patterns of bone marrow infiltration.Results There was no statistically significant difference in ADC values between the diffuse lesion in combined focal and diffuse infiltration group and the"salt-and-pepper"group(P＞0.99),and there was statistically significant difference in ADC values between the other groups(P＜0.05).The ROC curve showed that the area under the curve(AUC)for identifying focal group and the"salt-and-pepper"group was 0.889[95％confidence interval(CI)0.844-0.934],the AUC for identifying pure diffuse infiltration group and the normal appearance group was 0.968(95％CI 0.949-0.987).ADC values were able to accurately and visually differentiate between the different patterns of bone marrow infiltration.Conclusion The ADC values can be used as a quantitative tool to objectively distinguish different bone marrow infiltration patterns in MM patients.

Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.