Magnetic resonance angiography(MRA)is a non-invasive imaging technique used to observe blood vessels.Quantitative analysis of MRA images enables visualization of vascular pathways,condition,and blood flow dynamics,which is essential for diagnosing vascular diseases such as vascular lesions,stenosis,and occlusions.Vessel segmentation serves as the fundamental basis for quantitative vascular analysis.However,the complex morphology of vessels,difficulties in labeling,and scarcity of accurate 3D vascular annotations pose significant challenges for MRA-based vessel segmentation.A strategy of selectively occluding vessels during model training is proposed to enhance the algorithm's capacity to capture the topological structure of blood vessels,thereby improving the continuity of vessel segmentation results.Additionally,a Refine network is incorporated to refine the binary segmentation results of the segmentation network,thereby further improving segmentation accuracy.Model training and testing are carried out using 42 cases of 3D MRA data from the public MIDAS dataset.For the test set,the 3D U-Net baseline model with vessel occlusion strategy shows a β0 Error of 1.2742±0.2103 and a β1 Error of 0.3393±0.0818,respectively,which are 0.1136 and 0.0280 lower than the baseline.The model integrating vessel occlusion strategy and Refine network achieves an average Dice score of 0.7105±0.0125,which is 0.0028 higher than the baseline.These results demonstrate that the proposed method effectively improves both vascular connectivity and segmentation accuracy.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

Magnetic resonance angiography(MRA)is a non-invasive imaging technique used to observe blood vessels.Quantitative analysis of MRA images enables visualization of vascular pathways,condition,and blood flow dynamics,which is essential for diagnosing vascular diseases such as vascular lesions,stenosis,and occlusions.Vessel segmentation serves as the fundamental basis for quantitative vascular analysis.However,the complex morphology of vessels,difficulties in labeling,and scarcity of accurate 3D vascular annotations pose significant challenges for MRA-based vessel segmentation.A strategy of selectively occluding vessels during model training is proposed to enhance the algorithm's capacity to capture the topological structure of blood vessels,thereby improving the continuity of vessel segmentation results.Additionally,a Refine network is incorporated to refine the binary segmentation results of the segmentation network,thereby further improving segmentation accuracy.Model training and testing are carried out using 42 cases of 3D MRA data from the public MIDAS dataset.For the test set,the 3D U-Net baseline model with vessel occlusion strategy shows a β0 Error of 1.2742±0.2103 and a β1 Error of 0.3393±0.0818,respectively,which are 0.1136 and 0.0280 lower than the baseline.The model integrating vessel occlusion strategy and Refine network achieves an average Dice score of 0.7105±0.0125,which is 0.0028 higher than the baseline.These results demonstrate that the proposed method effectively improves both vascular connectivity and segmentation accuracy.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
Angiogenic Proteins/therapeutic use* ; Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Endothelial Cells ; Humans ; Nanoparticles ; Nucleic Acids/therapeutic use*

Objective:To investigate the diagnostic value of two-dimensional ultrasound combined with volumetric contrast imaging (VCI) and magnetic resonance imaging (MRI) for the developmental abnormalities of the fetal corpus callosum.Methods:Seventy-three fetuses who underwent cranial MRI within 1 week after suspected fetal corpus callosum dysplasia on ultrasound and received a definitive diagnosis in the neonatal period were retrospectively recruited for the study. The fetal corpus callosum was observed in the transverse, coronal, and sagittal views of the fetus, and the hyaline septal cavity, lateral ventricle, third ventricle, and corpus callosum were observed in the MRI scan. The diagnostic results and sensitivity of two-dimensional ultrasound combined with volumetric contrast imaging and MRI were analyzed.Results:Neonatal imaging showed that among 73 fetuses, 32 had agenesis of the corpus callosum, 29 had hypoplasia of the corpus callosum, and 12 had normal development of the corpus callosum. The differences in diagnostic results and sensitivity between 2D ultrasound combined with volumetric contrast imaging and MRI testing for agenesis of the corpus callosum were not statistically significant (all P>0.05), and the differences in diagnostic results and sensitivity for hypoplasia of the corpus callosum were statistically significant ( P<0.05). Conclusions:Both 2D ultrasound combined with volumetric contrast imaging and MRI are of high value for the diagnosis of partial-type agenesis of the corpus callosum, but MRI is more advantageous for the diagnosis of agenesis of the corpus callosum, and MRI can be a useful supplement and verification tool for ultrasound to provide a more accurate clinical diagnosis.

Objective To explore the characteristics of immunological changes in tree shrews infected with orthoreovirus, and provide a theoretical basis for the prevention of virus in tree shrews. Methods 40 -50-day-old tree shrews were divided into three groups: MRV1/TS/2011 virus-infected and MRV3/TS/2013 virus-infected groups, and saline-treated control group. On the 1, 8, 14, 21, and 28 days after infection, blood samples were taken from the tail vein and used for RT-PCR, flow cytometry and ELISA detection, to assess the viral load, number of CD4/CD8/CD19 cells, and IFN-gamma expression. Results The MRV1/TS/2011 and MRV3/TS/2013 viral load in the plasma and the number of CD4 +and CD19 +cells reached a peak at the 14th day after infection. At the first day after MRV1/TS/2011 infection, the CD4 +cells had a significantly higher expression compared with the normal group. CD8 +cells and the IFN-gamma expression reached a peak at the 21st day after infection. The expression of CD4 +was even higher after MRV1/TS/2011 infection, and the expression of CD8 +cells was higher after MRV3/TS/2013 infection. Conclusions We would conclude that after MRV1/TS/2011 and MRV3/TS/2011 virus infection, accompanying the changes of viral load, it shows some regularity of the expression of CD4/CD8/CD19 and IFN-gamma in the tree shrews: at the early stage of MRV1/TS/2011 virus infection, humoral immunity is stimulated, and CD4 +cells play a major role. MRV3/TS/2013 virus may mainly affect the cellular immunity, while humoral immunity only plays a role at a high viral expression or the late stage of infection. CD4 +cells may be more sensitive to type 1 reovirus, and CD19 +cells may be more sensitive to type 3 reovirus.

Objective To investigate the antitumor activity of the procaspase-3 activator SM-1 in BGC-823 cells in vivo and in vitro and the mechanisms.Methods The inhibitory effects of SM-1 on proliferation of BGC-823 cells were evaluated using MTT method, the cell apoptosis rate was detected by flow cytometry, and the expression of caspase-3 protein and procaspase-3 mRNA was detected by Western blotting and RT-PCR, respectively.SM-1 Antitumor activity was evaluated using the xenograft of BGC-823 cells in nude mice.Results SM-1 effectively inhibited the proliferation in vitro and in-duced apoptosis of BGC-823 cells in a dose-dependent manner.After treatment with SM-1 for 48 h, the protein expression levels of caspase-3 and mRNA expression levels of procaspase-3 were increased.SM-1 significantly inhibited growth of BGC-823 xenograft tumor at the 300 mg/kg dose and the inhibition rate was 56.3%(P<0.05).Conclusion SM-1 can significantly inhibit the tumor growth of BGC-823 cells in vivo and in vitro.The mechanism is possibly related to the activation of procaspase-3 and induced apoptosis of tumor cells.

Objective To investigate the diagnostic value of cyclophilin A(CyPA)for chronic heart failure (CHF).Methods Eighty pateints,made a definite diagnosis as CHF,were classified 30 cases as A phase,29 cases as C phase,21 cases as D phase of them.30 healthy subjects were enrolled in this study.Serum CyP A was detcted by ELISA.NT-proBNP was detec-ted with Roche Cobas 6 000 automatic electrochemilu-minescence immunoassay system.Results The amounts of serum CyP A(x-±s,ng/ml)in healthy subjects and each group with CHF were 110.10±49.73,327.85±82.67,331.70±69.34 and 342.46±92.55.Using Oneway Anova,CyP A concentration of CHF was significantly higher than healthy controls (F=58.45,P<0.01).Further using Post Hoc Tests-Multiple Comparisons,the CyP A concentration of each group with CHF was significantly higher than the healthy control group (Mean differences were 217.75~232.36,P<0.01),but showed no significant difference between the groups with CHFs (Mean differences were 3.37~14.61,P>0.05).Results of ROC curves showed the AUC (CyP A)was 0.97.The best cutoff value was 198.39 (ng/ml).The sensitivity was 91.30%,the specificity was 93.30%.The correlation analysis showed that CyP A and NT-proBNP were correlated (r=0.30,P<0.01). CyP A and NT-proBNP combined detections showed the sensitivity was 93.80% and the specificity was 100%.Conclusion The Cyp A levels in CHF group are significantly higher than the control group,suggesting that Cyp A may be a factor for CHF appearance.These results indicate that combined detections may helpful to early diagnosis of CHF.

Objective To investigate the significance of Ang-Ⅱ in diagnosis of chronic heart failure.Methods Eighty patients with chronic heart failure were divided into 3 groups:A phase with 30 cases,as C phase with 29 cases and D phase with 21 cases.30 healthy subjects were enrolled in this study.Serum Ang-Ⅱ was detected by ELISA.NT-proBNP was detected with Roche Co-bas6000 automatic electrochemiluminescence immunoassay system.Results Using Oneway Anova,the Ang-Ⅱconcentration of pa-tients with chronic heart failure was significantly higher than that of the healthy subjects (F =38.35,P <0.01).Further using Post Hoc Tests-Multiple Comparisons,the Ang-Ⅱ concentration of each group with chronic heart failure was significantly higher than that of the healthy control group.Results of ROC curves showed the aera under the curve of Ang-Ⅱwas 0.92.The best cutoff value was 552.25 (ng/mL).The sensitivity was 90.00%,and the specificity was93.30%.The correlation analysis showed that Ang-Ⅱwere correlated with NT-proBNP(r=0.23,P <0.05).The sensitivity and the specificity of combined detection of Ang-Ⅱand NT-proBNP were 98.80% and 100%,respectively.Conclusion The Ang-Ⅱlevels in chronic heart failure groups are significantly high-er than that in the control group,which indicates that combined detection may be helpful to the early diagnosis of chronic heart fail-ure.