OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1（SLC25A25-AS1）. METHODS Using BALB/c nude mice as the subjects， the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin （20 and 40 mg/kg） on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group， isorhamnetin group （70 μmol/L， similarly hereinafter）， isorhamnetin+knocking down negative control group， isorhamnetin+knocking down SLC25A25-AS1 group， isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability， apoptosis， migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p （miR-212-3p） and SLC25A25-AS1， as well as phosphatase and tensin homologue deleted on chromosome 10 （PTEN）， the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p， PTEN mRNA， and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group， tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly， and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group （P＜0.05）. miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group， the cell viability （intervened for 24， 48 h）， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin group， isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly increased or up-regulated （P＜0.05）. Compared with isorhamnetin group and isorhamnetin+knocking down negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly reduced or down-regulated （P＜ 0.05）. Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated， while the apoptosis rate， PTEN mRNA and protein expressions were significantly increased or up-regulated （P＜0.05）. CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1， down-regulating miR-212-3p， and up-regulating the expression of PTEN， which is a downstream target of miR-212-3p.

OBJECTIVE To explore the effects of limonin on renal lesions， glucose metabolism， inflammation， and oxidative stress in gestational diabetic rats and its possible mechanisms. METHODS The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group （intragastrical administration and tail vein injection of equal volume of normal saline）， limonin low-， medium-， and high-dose groups （intragastrical administration of limonin， at doses of 12.5， 25.0 and 50.0 mg/kg， and equal volume of normal saline into the tail vein）， and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun N-terminal kinase （JNK） activator Anisomycin 2 mg/kg ]， with 12 rats in each group. In addition， 12 pregnant rats were selected as the control group （intragastrical administration and tail vein injection of equal volume of normal saline）. They were given relevant medicine， once a day， for 14 consecutive days. After the last administration， fasting blood glucose （FBG）， the levels of fasting insulin （FINS）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum were detected； the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， blood urea nitrogen （BUN）， and creatinine （Cr） in the renal tissue were detected； the pathological changes of renal tissue were observed； the expressions of proteins related to the JNK/nuclear factor-κB （NF-κB） signaling pathway in the renal tissue were detected. RESULTS Compared with control group， in model group， the rats showed pathological injuries in the kidney tissue， such as glomerular atrophy， edema of renal tubular epithelial cells； the levels of FBG， FINS， IL-1β， IL-6， TNF-α， MDA， BUN and Cr， HOMA-IR， as well as the phosphorylation levels of JNK and NF-κB 0453-6602005。E-mail：mcvi45@163.com p65 proteins were increased significantly （P＜0.05）， while the levels of SOD and GSH-Px were decreased significantly （P＜0.05）. Compared with model group， in each dose group of limonin， the degree of renal tissue lesions in rats was alleviated， and the above-mentioned indicators were significantly improved （P＜0.05）， showing an obvious dose-effect relationship （P＜0.05）. Compared with high-dose limonin group， in the combination group， the degree of renal tissue lesions in rats was relatively aggravated， and the changes in the above-mentioned indicators were significantly reversed （P＜0.05）. CONCLUSIONS Limonin has a certain improvement effect on renal lesions， glucose metabolism， inflammation， and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

OBJECTIVE To evaluate the quality of Euscaphis japonica from different habitats. METHODS The relative correction factors of gallic acid， protocatechuic acid， ellagic acid， isoquercitrin， astragalin and apigenin were calculated with quercetin as the internal reference； the relative correction factors of euscaphic acid， oleanolic acid， stigmasterol and β-sitosterol were also calculated with ursolic acid as the internal reference. The contents of 12 components in 18 batches of samples were calculated by QAMS method and were compared with external standard method. At the same time， the contents of water-soluble extract， alcohol-soluble extract， total ash and acid-insoluble ash were detected. The quality of E. japonica was evaluated by principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， and weighted technique for order preference by similarity to ideal solution （TOPSIS） method. RESULTS There was no significant difference between the results of QAMS method and external standard method for the 12 components in the 18 batches of samples. However， notable content variations were observed among different batches of samples. The results of PCA and OPLS-DA showed that S1-S7， S8- S12， and S13-S18 were clustered into one category respectively. Seven key characteristic components variable importance in projection values ＞1， euscaphic acid， ursolic acid， protocatechuic acid， apigenin， β-sitosterol， isoquercitrin， and oleanolic acid， respectively. The analysis results of the weighted TOPSIS method revealed that the relative closeness for evaluating the quality of 18 batches of samples ranged from 0.283 5 to 0.644 1， with the samples of E. japonica from Fengjie， Chongqing， demonstrating the highest quality. CONCLUSIONS The established method is accurate and feasible， which can be used for the quality evaluation of E. japonica combined with chemometrics and weighted TOPSIS model.

OBJECTIVE To investigate the potential mechanism of epigallocatechin gallate （EGCG） enhancing the sensitivity of hepatocellular carcinoma （HCC） cells to lenvatinib based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS Five human HCC cell lines （HepG2， Huh-7， SMMC-7721， SNU-368 and SNU-739） were used to evaluate the effects of lenvatinib alone and in combination with EGCG on survival rates， clone number， proliferation rate， invasion number and the expressions of mRNAs and proteins related to the PI3K/Akt signaling pathway. The PI3K activator insulin-like growth factor-1 （IGF-1） was introduced to investigate the effect of activating the PI3K/Akt signaling pathway on the sensitization effect of EGCG. RESULTS Compared with the control group， lenvatinib （10 μmol/L） and different concentrations of EGCG+ lenvatinib （1， 5 and 10 μg/mL EGCG+10 μmol/L lenvatinib） significantly reduced the survival rates and clone numbers of all five HCC cell lines in a dose-dependent manner （P＜0.05）. Lenvatinib （10 μmol/L） and EGCG+lenvatinib （10 μg/mL EGCG+10 μmol/L lenvatinib） also markedly inhibited the proliferation rate and invasion numbers of these cells， and decreased the mRNA expressions of PI3K， Akt， mammalian target of rapamycin （mTOR）， P70S6K and 4EBP， and the phosphorylation levels of PI3K and Akt， as well as the protein expressions of mTOR and B cell lymphoma-2 （Bcl-2） in HepG2 cells or all five HCC cells； conversely， the mRNA and protein expressions of phosphatase and tensin homologue deleted on chromosome 10（PTEN）， and the protein expressions of caspase-3 and cleaved caspase-3 were significantly upregulated， with more pronounced effects observed in the EGCG+lenvatinib group than in the lenvatinib group （P＜0.05）. Compared with the lenvatinib group and the EGCG+lenvatinib group， the clone number， proliferation rate and invasion number of HepG2 cells in the EGCG+lenvatinib+IGF-1 group （10 μg/mL EGCG+10 μmol/L lenvatinib+50 ng/mL IGF-1） were significantly increased （P＜0.05）. CONCLUSIONS EGCG can enhance the sensitivity of HCC cells to lenvatinib， and its underlying mechanism may be related to the inhibition of the activation of PI3K/Akt signaling pathway activation.

Objective To evaluate the correlation between 3D morphological parameters of aneurysms based on the computer-assisted semi-automated measurement and the risk of aneurysm rupture.Methods From October 2019 to October 2022,patients with ruptured multiple aneurysms admitted to the Department of Neurosurgery of Xuanwu Hospital,Capital Medical University were retrospectively included.Aneurysmal morphological parameters(including aneurysmal diameter,maximum diameter,width,neck width,volume,flow angle,parental artery diameter,surface area,wave index and non-spherical index)were measured by computer-assisted semi-automated measurement methods.The length-to-width ratio,wide-to-neck ratio,aspect ratio and size ratio were calculated,and the aneurysm location information was recorded.The ruptured aneurysms in multiple aneurysms were included in the ruptured group,and the remaining aneurysms were included in the unruptured group.Uni variable analysis and binary Logistic analysis were used to evaluate the differences in morphological parameters and location information between the ruptured and unruptured groups.Results All 56 patients with multiple ruptured aneurysms and a total of 126aneurysms were included in the group for analysis.Concerning morphology,including diameter＞5 mm(51.8％[29/56]vs.15.7％[11/70],P＜0.01),maximum diameter＞6mm(57.1％[32/56]vs.25.7％[18/70],P＜0.01),flow angle＞107°(57.1％[32/56]vs.35.7％[25/70],P=0.016),wide-to-neck ratio＞1.1(50.0％[28/56]vs.30.0％[21/70],P=0.022),aspect ratio＞1.1(46.4％[26/56]vs.25.7％[18/70],P=0.015)and size ratio＞1.9(57.1％[32/56]vs.10.0％[7/70],P＜0.01),there was significant difference between the ruptured and unruptured group;Concerning locations,aneurysms are mainly located in the posterior communicating segment of the internal carotid artery(39.3％[22/56])and the middle cerebral artery(23.2％[13/56])in ruptured group,while in the middle cerebral artery(28.6％[20/70])and the non-posterior communicating segment of internal carotid artery(27.1％[19/70])in unruptured group,and there was significant difference in distribution of aneurysm locations(P=0.003).Multivariate Logistic regression analysis showed that size ratio＞1.9 was an independent risk factor for aneurysm rupture(OR,11.62,95％CI 2.40-56.15;P=0.002).Concerning locations,posterior communicating artery aneurysms had a significantly higher risk of rupture compared with the non-posterior communicating segment of internal carotid artery(OR,19.25,95％CI 2.19-169.51;P=0.008).Conclusion For multiple intracranial aneurysms,the size ratio of the three-dimensional morphological parameters of aneurysms＞1.9 is an independent risk factor for aneurysm rupture,and the rupture risk of posterior communicating artery aneurysms is significantly higher than that of non-posterior communicating segment of internal carotid artery.

Objective To create a semi-automatic technology based on convolutional neural networks for saccular aneurysm segmentation.Methods The single-center data of Xuanwu Hospital of Capital Medical University in the database of"China Intracranial Aneurysm Program"from July 2017 to July 2020 were retrospectively included,and all data were anonymized before analysis.Baseline data were collected from all patients,including sex,age(≥60 years and＜60 years),DSA model,number of DSA sequences,and aneurysm information,including the number of aneurysms,diameter(≥5 mm and＜5 mm),neck width(wide neck,narrow neck),and location(bifurcation,sidewall).According to the ratio of 8∶1∶1,the data were randomly divided into training set,test set and validation set by random number table method.The DSA 3D tomography data of all patients were completed in the contrast machine using the 3D rotary DSA mode,and the aneurysms shown in the DSA 3D tomography data were annotated by 3 experienced neurosurgeons,and the standard label of the aneurysm was finally generated.The proposed aneurysm segmentation method consisted of a training stage and a segmentation stage.In the training stage,the model was trained end-to-end by using the DSA 3D tomography image data of the training set,the segmentation label of the aneurysm and the vascular edge information extracted by the Marching Cubes algorithm,and the segmentation index of the model was monitored on the test set to retain the model with the highest segmentation index.In the segmentation stage,the physician selects a point inside the aneurysm on the DSA 3D tomography image of the aneurysm in the validation set,intercepts the volume of interest(VOI),inputs the trained optimal model of vascular and aneurysm segmentation,obtains the segmentation result of the aneurysm,and locates the segmented VOI back to the original DSA 3D tomography image to obtain the final aneurysm outline.The segmentation results of the segmentation network model were compared with standard labels to calculate the Dice similarity coefficient(DSC).The validation set data was stratified by aneurysm diameter,neck width,and location to compare the segmentation results in different datasets.We calculated the bounding boxes for the length,width,and height of the aneurysm segmentation mask,and used the maximum of these as the longest diameter of the aneurysm compared to the maximum diameter in the standard label.In the validation set,the standard label manual acquisition time was counted and compared with the segmentation network model acquisition time(from the time of locating the aneurysm to obtaining a satisfactory aneurysm neck segmentation).Results Finally,969 DSA sequences from 756 patients were included to show 3D tomographic data for 1 094 aneurysms.Among them,604 patients with 877 aneurysms with a total of 783 DSA sequences were included in the training set,117 aneurysms with a total of 100 DSA sequences in 77 patients were included in the test set,and 100 aneurysms with a total of 86 DSA sequences were included in 75 patients in the validation set.(1)The baseline comparison results of each dataset showed that there were statistically significant differences between the datasets of aneurysm diameter(P=0.003)and aneurysm location(P=0.003).There was no significant difference between the remaining baseline data sets(all P＞0.05).(2)The mean DSC of centralized aneurysm segmentation was 0.868±0.078.The mean DSC of aneurysm segmentation≥5 mm diameter was higher than that of aneurysms with＜5 mm diameter(0.891±0.041 vs.0.855±0.088,P=0.038).The DSC values of narrow-necked,wide-necked,bifurcated and lateral wall aneurysms were 0.882±0.065,0.859±0.085,0.876±0.072 and 0.863±0.080,respectively,and there was no significant difference between the groups(all P＞0.05).(3)The maximum diameter of the mask obtained by the aneurysm segmentation model in the validation set was in good agreement with the maximum diameter of the standard label obtained by manual segmentation([5.78±3.18]mm vs.[5.37±2.92]mm,r=0.97).In the validation set,the average time of manual segmentation and neural network segmentation of aneurysms was 2.5 min and 34 s,respectively.Conclusion In this study,a semi-automatic saccular aneurysm segmentation technique based on convolutional neural network can accurately segment aneurysms and is helpful to improve aneurysm morphology analysis.