ObjectiveTo explore the mechanism by which exosomes derived from gastric cancer cells MGC-803 promote tumor progression through the upregulation of ABCG8 expression. MethodsUltra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） lipidomics， quantitative real-time PCR （qPCR） and Western blot were used to verify the role of ABCG8 in gastric cancer progression. Exosomes derived from gastric cancer cells were introduced， and a series of in vitro experiments were conducted to evaluate their effect on ABCG8 expression， as well as on cell proliferation， migration， and clonogenic ability in normal gastric mucosal epithelial GES-1 cells. ResultsUPLC-MS/MS lipidomics analysis revealed significant changes in triacylglycerol （TG） among the differential lipids. qPCR and Western blot analysis showed that the mRNA and protein expression levels of ABCG8 in the GC-Exo-treated group were higher than those in the GES-1 cell group （P<0.05）. Colony formation and Transwell migration assays revealed that， compared with the GES-1 cell group， the GC-Exo-treated group exhibited a greater number of colonies （P<0.05） and migrated cells （P<0.05） after 48 h of treatment. CCK-8 assay results showed that the proliferation rate in the GC-Exo-treated group （50 μg/mL） was higher than that in the GES-1 cell group （P<0.001）. Lipidomics analysis revealed that， compared with the GES-1 cell group， TG levels were upregulated in the GC-Exo-treated group， accompanied by decreased levels of phosphatidylcholine （PC） PC（38：2e）. ConclusionExosomes derived from gastric cancer cells MGC-803 may promote tumor progression by upregulating ABCG8 expression to mediate cholesterol efflux， thereby triggering pro-carcinogenic lipid metabolic reprogramming in normal gastric mucosal epithelial cells.

OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

Objective:To investigate the reliability and validity of different measurement methods under 30° arthroscopy for quantifying the proportion of glenoid bone defect in bony Bankart lesions of the shoulder joint and validate its preliminary application effect.Methods:Eight intact shoulder glenoid specimens were selected, with no existing defects or deformities, from donors of 4 females and 4 males, with their age at death of 43-67 years [(54.4±8.0)years]. Bone defects of 12.5% and 25% were created in the glenoid at 0° and 45° relative to the longitudinal axis, with two specimens per defect category. The defect proportion in each specimen was quantified using direct measurement and CT-based digital reconstruction and these values served as reference standards for subsequent statistical analysis. Using a combined approach of arthroscopic simulation equipment and cadaveric study, five investigators performed simulated examinations through the standard posterior portal (2 cm medial and 1.5 cm inferior to the posterolateral acromial corner) and the modified posteroinferior portal (2 cm medial and 3 cm inferior to the posterolateral acromial corner) separately. Under 30° arthroscopy, the glenoid bone loss percentage was measured using the bare spot method and secant chord method. The reliability was analyzed for these measurements. Furthermore, using direct physical measurements and CT-based three-dimensional reconstruction data from the same specimens as reference standards, the comprehensive validity of four measurement methods was evaluated (standard posterior portal-bare spot method, standard posterior portal-secant chord method, modified posteroinferior portal-bare spot method, and modified posteroinferior portal-secant chord method). The independent validity of each method was assessed according to bone defect morphology classification to determine differences in measurement accuracy across defect types. In an arthroscopic procedure for a patient with Bigliani type IIIB bony Bankart lesion, the standard posterior portal-secant chord method was applied to quantify the proportion of glenoid bone defects.Results:The mean reference values from direct measurement and CT measurement of glenoid bone defect proportion in eight bony Bankart lesion specimens were 12.71%/12.37%, 13.17%/13.10%, 25.71%/24.9%, 26.6%/26.95%, 13.41%/13.10%, 12.90%/12.59%, 26.42%/25.94%, and 26.73%/27.06%, respectively. Measurements obtained by the five investigators showed intraclass correlation coefficients (ICCs) all greater than 0.90, indicating excellent interobserver agreement. In the validity analysis, the standard posterior portal-secant chord method demonstrated the highest overall validity. Using direct measurement and CT-based measurement as reference standards, the overall validity was (0.90±0.38)% and (1.07±0.53)% for the standard posterior portal-bare spot method, (1.33±0.40)% and (1.51±0.54)% for the modified posteroinferior portal-bare spot method, and (0.53±0.17)% and (0.70±0.38)% ( P<0.05) for the modified posteroinferior portal-secant chord method. In contrast, the standard posterior portal-secant chord method showed an overall validity of (0.10±0.10)% and (0.28±0.39)% ( P>0.05). In subsequent independent validity analyses, the standard posterior portal-secant chord method also demonstrated superior validity across all bone defect subtypes over the other three methods. In a patient with a Bigliani type IIIB bony Bankart lesion, we used the standard posterior portal-secant chord method to quantify the glenoid bone loss in 2 minutes, revealing a defect proportion of 26.6%. An arthroscopic autologous iliac bone graft procedure with single-tunnel elastic fixation guided by this measurement achieved favorable outcomes, with stable reduction, secure internal fixation and favorable recovery of shoulder function at 2 months postoperatively. Conclusion:For various types of bony Bankart lesions, the 30° arthroscopic standard posterior portal-secant chord method provides the most accurate quantification of glenoid bone loss and its preliminary clinical application yields satisfactory results.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

BACKGROUND:With the continuous advancement of medical technology,the combination of oblique lumbar interbody fusion and percutaneous pedicle screw fixation has become a common method for treating lumbar degenerative diseases;however,there is still a lack of in-depth research on the relationship between changes in anterior convexity angles at different postoperative segments and fusion device settlement.OBJECTIVE:To explore the relationship between changes in anterior convexity angle of different segments and Cage subsidence after oblique lumbar interbody fusion combined with percutaneous pedicle screw fixation surgery.METHODS:Patients(93 cases)with lumbar degenerative diseases who underwent oblique lumbar interbody fusion combined with percutaneous pedicle screw fixation surgery in Weifang Hospital of Traditional Chinese Medicine from February 2019 to April 2023 were selected as the research subjects.According to the postoperative disc height loss value,they were divided into Cage subsidence group(25 cases,＞2 mm)and non-Cage subsidence group(68 cases,＜2 mm).Multiple Logistic regression analysis was used to analyze the risk factors for cage subsidence.Stepwise regression was utilized to evaluate the relationship of each risk factor and Cage subsidence.Risk prediction model was built and evaluated.RESULTS AND CONCLUSION:(1)After adjusting for confounding factors,there was still independent correlation between lumbar lordosis loss value and segmental lordosis improvement value and Cage subsidence risk(P＜0.05).(2)Age,oswestry disability index,disc height improvement value,segmental lordosis improvement value,and lumbar lordosis loss value were all independent influencing factors for the occurrence of Cage subsidence(P＜0.05).Among them,age,lumbar lordosis loss value,disc height improvement value,and segmental lordosis improvement value were most closely related to Cage subsidence.(3)The results of multivariate Logistic regression model analysis showed that when P=0.80,the Jordan index was the highest and the prediction effect was the best,with accuracy of 89.27％,sensitivity of 86.67％,and specificity of 89.89％.The model evaluation results showed that it had good discrimination and high accuracy.(4)As the lumbar lordosis loss value and segmental lordosis improvement value increase,the risk of Cage subsidence increases,which affects clinical efficacy.(5)It is indicated that age,lumbar lordosis loss value,disc height improvement value,and segmental lordosis improvement value are most closely related to Cage subsidence,and clinical doctors should pay more attention.

Objective:To investigate the reliability and validity of different measurement methods under 30° arthroscopy for quantifying the proportion of glenoid bone defect in bony Bankart lesions of the shoulder joint and validate its preliminary application effect.Methods:Eight intact shoulder glenoid specimens were selected, with no existing defects or deformities, from donors of 4 females and 4 males, with their age at death of 43-67 years [(54.4±8.0)years]. Bone defects of 12.5% and 25% were created in the glenoid at 0° and 45° relative to the longitudinal axis, with two specimens per defect category. The defect proportion in each specimen was quantified using direct measurement and CT-based digital reconstruction and these values served as reference standards for subsequent statistical analysis. Using a combined approach of arthroscopic simulation equipment and cadaveric study, five investigators performed simulated examinations through the standard posterior portal (2 cm medial and 1.5 cm inferior to the posterolateral acromial corner) and the modified posteroinferior portal (2 cm medial and 3 cm inferior to the posterolateral acromial corner) separately. Under 30° arthroscopy, the glenoid bone loss percentage was measured using the bare spot method and secant chord method. The reliability was analyzed for these measurements. Furthermore, using direct physical measurements and CT-based three-dimensional reconstruction data from the same specimens as reference standards, the comprehensive validity of four measurement methods was evaluated (standard posterior portal-bare spot method, standard posterior portal-secant chord method, modified posteroinferior portal-bare spot method, and modified posteroinferior portal-secant chord method). The independent validity of each method was assessed according to bone defect morphology classification to determine differences in measurement accuracy across defect types. In an arthroscopic procedure for a patient with Bigliani type IIIB bony Bankart lesion, the standard posterior portal-secant chord method was applied to quantify the proportion of glenoid bone defects.Results:The mean reference values from direct measurement and CT measurement of glenoid bone defect proportion in eight bony Bankart lesion specimens were 12.71%/12.37%, 13.17%/13.10%, 25.71%/24.9%, 26.6%/26.95%, 13.41%/13.10%, 12.90%/12.59%, 26.42%/25.94%, and 26.73%/27.06%, respectively. Measurements obtained by the five investigators showed intraclass correlation coefficients (ICCs) all greater than 0.90, indicating excellent interobserver agreement. In the validity analysis, the standard posterior portal-secant chord method demonstrated the highest overall validity. Using direct measurement and CT-based measurement as reference standards, the overall validity was (0.90±0.38)% and (1.07±0.53)% for the standard posterior portal-bare spot method, (1.33±0.40)% and (1.51±0.54)% for the modified posteroinferior portal-bare spot method, and (0.53±0.17)% and (0.70±0.38)% ( P<0.05) for the modified posteroinferior portal-secant chord method. In contrast, the standard posterior portal-secant chord method showed an overall validity of (0.10±0.10)% and (0.28±0.39)% ( P>0.05). In subsequent independent validity analyses, the standard posterior portal-secant chord method also demonstrated superior validity across all bone defect subtypes over the other three methods. In a patient with a Bigliani type IIIB bony Bankart lesion, we used the standard posterior portal-secant chord method to quantify the glenoid bone loss in 2 minutes, revealing a defect proportion of 26.6%. An arthroscopic autologous iliac bone graft procedure with single-tunnel elastic fixation guided by this measurement achieved favorable outcomes, with stable reduction, secure internal fixation and favorable recovery of shoulder function at 2 months postoperatively. Conclusion:For various types of bony Bankart lesions, the 30° arthroscopic standard posterior portal-secant chord method provides the most accurate quantification of glenoid bone loss and its preliminary clinical application yields satisfactory results.

Objective To analyze the expression and clinical significance of stimulator of interfer-on genes(STING),C-C motif chemokine ligand 5(CCL5),interferon regulatory factor 3(IRF3)and programmed death ligand-1(PDL1)in squamous cell lung cancer.Methods A total of 56 pa-tients with squamous cell lung cancer were enrolled.Resected tumor tissues and adjacent non-tumor tissues(located more than 5 cm from the tumor margin)were collected.Immunohistochemical staining was performed to detect the expression of STING,CCL5,IRF3 and PDL1.The correlations of STING,CCL5,IRF3 and PDL1 with clinical data were analyzed.The relationship between the expression of STING,CCL5,IRF3 and PDL1 in lung squamous cell carcinoma tissues and prognosis was also evalua-ted.The prognostic factors of patients with lung squamous cell carcinoma were analyzed.Results The positive rate of STING expression in lung squamous cell carcinoma tissues was significantly lower than that in adjacent non-tumor tissues,whereas the positive rates of CCL5,IRF3 and PDL1 were significantly higher(P＜0.05).The expression levels of STING,CCL5,IRF3 and PDL1 were associated with tumor diameter,TNM stage,lymph node metastasis and differentiation degree(P＜0.05).The 3-year survival rate of STING positive expression patients was significantly higher than that of STING negative expression patients(P＜0.05).The 3-year survival rate of CCL5 positive,IRF3 positive and PDL1 positive expression patients was significantly lower than that of CCL5 negative,IRF3 negative and PDL1 negative expression patients(P＜0.05).STING,CCL5,IRF3 and PDL1 were identified as prognostic factors for patients with squamous cell lung cancer(P＜0.05).Conclusion In squamous cell lung cancer tissues,STING is expressed at low levels,while CCL5,IRF3 and PDL1 are ex-pressed at high levels.These findings have significant clinical value in assessing the prognosis of pa-tients with squamous cell lung cancer.

Objective To develop an ultra high performance liquid chromatography-mass spectrometry(UPLC-MS)method for quantifying serum levels of norepinephrine(NE)and 5-hydroxytryptamine(5-HT),and to monitor the dynamic changes in these neurotransmitters during the process of establishing a model of acute reserpine-induced depression-like mice.Methods By evaluating matrix effect,recovery,precision,and accuracy efficiency,an UPLC-MS method for determining the concentrations of NE and 5-HT in serum was established.Forty-eight C57 mice were randomly divided into normal control and model groups,which were intraperitoneally injected with physiological saline(10 mL/kg)and reserpine(2.5 mg/kg),respectively.At various time points after intraperitoneal injection,the degree of ptosis and decreases in body temperature of the mice were observed before orbital blood was sample for the determination of NE and 5-HT levels.Results The concentrations of NE and 5-HT showed good linearity within the range of 15.63 to 2000.00 ng/mL,with R2 values greater than 0.999.The results of methodological validation met the requirements for the analysis of biological samples,with a lower limit of quantification of 15.63 ng/mg.After intraperitoneal injection of reserpine,the model mice exhibited varying body temperature decreases and ptosis.At 1 and 2 h post-administration,the depression-like symptoms in the model group were significantly different from those of the normal control group(P＜0.01).The body temperature of mice in the model group was significantly lower than that of mice in the normal control group(P＜0.01),while the score of the eyelid ptosis was significantly higher(P＜0.001).The levels of NE and 5-HT in the serum of model mice were also significantly depleted,and were significantly different from those of the normal control group at 0.5,1 and 2 h(P＜0.05).Conclusion The study process of established a rapid and accurate method for dynamically observing the changes in NE and 5-HT levels during the process of establishing a model of acute reserpine-induced depression-like mice,which might contribute to the study of the pathogenesis of depression and the development of new antidepressant drugs.

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.