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Heterophyllin B (HB) is a cyclic lipopeptide that has been shown to have anticancer effects. This study intended to further explore the effects and modulatory mechanism of HB in gastric cancer (GC) cells. The binding relationship between HB and CXCR4 was investigated by network pharmacological analysis, molecular docking, and cellular thermal shift assay (CETSA)-WB assay. Cellular assays revealed that HB could restrain GC cell viability, proliferation, invasion and migration by binding to CXCR4. Further studies presented that HB could suppress PI3K/AKT signaling pathway via binding to CXCR4, thus repressing PD-L1 expression. In vivo experiments in nude mice demonstrated that HB constrained PI3K/AKT signaling pathway to suppress GC cell metastasis and PD-L1 expression. In summary, the key target of HB in GC treatment was CXCR4. Cell experiments were employed for the investigation of the mechanism by which HB repressed GC cells. The results confirmed that HB could constrain the malignant progression of GC by the binding of HB into CXCR4 and suppressed PD-L1 expression via hampering PI3K/AKT signaling pathway.

Radix Pseudostellariae, a traditional Chinese medicine, functions in modulating human immunity and anti-tumor, but its pharmacological mechanism remained unclear. In this study, 8 active components and 91 targets of Radix Pseudostellariae were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and 225 genes related to gastric cancer (GC) were accessed from MalaCards. On the basis of these targets and GC-related genes, a protein-protein interaction (PPI) network was established. Random walk with restart (RWR) analysis was performed on the PPI network with the intersection of targets and GC-related genes as the seeds. The top 50 target genes with high affinity scores were obtained. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the enrichment of the top 50 genes was mostly presented in the cancer-related biological functions and signaling pathways, such as cellular response to oxidative stress, regulation of apoptotic signaling pathway, and P53 signaling pathway. A drug-component-target network was established, with the top 50 genes being used as key targets. Acacetin and luteolin were revealed to directly act on the core target TP53 in the network. Thus, SwissDock was used to simulate the molecular docking between TP53 protein and acacetin and luteolin. The results of docking simulation presented small estimated ΔG of two small molecules, which were suggested to be potential targets of TP53 protein. Subsequent cellular and molecular experiments confirmed this bioinformatics result. In conclusion, this study predicted the key anti-GC active components and corresponding targets of Radix Pseudostellariae through bioinformatics analysis. The findings underlie the anti-GC mechanism of Radix Pseudostellariae.

Background It is still a challenge to choose the most appropriate endovascular treatment strategy for intracranial aneurysms. In this study, we aimed to investigate the application of AneuPlan™, based on computational fluid dynamics analysis, in the surgical planning of intracranial aneurysms.Methods: 9 patients with intracranial aneurysm were enrolled, whose surgical planning was made according to the Surgical Planning Program analysis, before endovascular treatment. Clinical characteristics, procedural details, stimulated hemodynamics analysis after surgery, site effect and 6-month follow-up were recorded. A descriptive analysis was performed.Results: Among the 9 patients, 5 patients received flow diverter implantation, 3 patients received stent-assisted coiling and 1 patient received simple coiling. The velocity of blood flow into the aneurysm and wall shear stress of the aneurysm were obviously reduced. No hemorrhagic or ischemic complication occurred in all patients. No recurrence of the aneurysm at 6-month follow-up.Conclusions: The good clinical prognosis obtained according to the Surgical Planning Program shows its potential for the optimization of the endovascular treatment for intracranial aneurysms.

Increasing evidence shows that Transmembrane 4 L6 family member 1(TM4SF1) exerts a critical role in mediating the progression of various tumors. Nevertheless, the exact mechanism of TM4SF1 in gastric cancer (GC) remains unclear.Bioinformatics analysis was utilized to analyze TM4SF1 expression in GC tissues. Also, MiRWalk and starBase databases were used to predict the upstream microRNAs which could regulate TM4SF1 expression. Gene set enrichment analysis (GSEA) for TM4SF1 was conducted to screen the potentially involved pathways. Dysregulation of microRNA-501-3p/TM4SF1 was implemented to investigate the regulatory roles of these genes in GC. qRT-PCR and western blot were employed to measure the expression changes of microRNA-501-3p, TM4SF1, and epithelial-mesenchymal transition (EMT) signaling pathway-associated proteins. CCK-8, colony formation, and transwell assays were introduced to examine the biological functions of GC cell lines.TM4SF1 presented a significantly low level in mRNA and protein in GC cells. MicroRNA-501-3p could target TM4SF1 and reduce its expression. Cell function experiments revealed that microRNA-501-3p facilitated cell proliferation, migration, and invasion, while inhibiting cell apoptosis in GC by targeting TM4SF1. EMT-associated proteins were altered by changing microRNA-501-3p/TM4SF1 axis.MicroRNA-501-3p regulated EMT signaling pathway by down-regulating TM4SF1 expression and therefore facilitated the malignant progression of GC, which may provide a new potential therapeutic target for the treatment of GC patients.

Background: Self-expanding devices, such as the Enterprise VRD (EP-VRD) have widely used for stent-assisted coiling treatment in wided-necked aneuryms while some thromboembolic complications were reported due to its incomplete stent apposition (ISA). We report our experiences on the novel Enterprise2 (EP-VRD2) stent in vivo in the treatment of intracranial and cranial cervical junction aneurysms.Methods: Twenty-five consecutive patients with intracranial or cranial cervical junction aneurysms were treated with EP-VRD2 stents retrospectively collected in our institution. We use the ‘jailing' technique in all cases and deployed the stent by using pushing over the outer curve technique. The 3- or 6-monthS follow-up was done regularly by DSA.Results: Twenty-five EP-VRD2 stents were implanted to treat 21 aneurysms at the siphon segment of internal carotid artery (ICA), one at the petrous segment, two at the cervical segment, one at the verteral artery with five accompanied with stenosis. Two patients had kinking during the procedure and were solved by microwire or microcatheter massaging. Four patients with a larger arc angle and a smaller radius of the parent vessel was detected ISA. No patient underwent the ischemic event after the operation. Twenty-three of 25 patients were evaluated after 3- or 6-months by DSA, 22 showed complete occlusion (RROC1), one slight re-stenosis in the follow-up within those five patients with stenosis. A length of 23 mm seemed associated with ISA (p < 0.01).Conclusion: The EP-VRD2 performed well in our small patient series; however, ISA could still occur with a sharp angle of the parent vessel.

Alzheimer's disease (AD) is one of the most common types of dementia among the elderly. Previous studies had revealed that the dysregulation of lncRNAs played important roles in human diseases, including AD. However, there is still a lack of comprehensive analysis of differently expressed long non-coding RNAs (lncRNAs) in different distinct regions related to AD. In present study, we identified a total of 678, 593, 941, 1445, 1179, 466 differently expressed lncRNAs that were found in entorhinal cortex (EC), middle temporal gyrus(MTG), hippocampus (HIP), superior frontal gyrus (SFG), posterior cingulate (PC), cortex and primary visual cortex (VCX) AD samples, respectively. Furthermore, we constructed lncRNA-mRNA co-expression networks in AD to explore the potential roles of these lncRNAs. Differentially expressed (DE) lncRNAs were involved in regulating metabolic process, respiratory electron transport chain and ATP metabolic process showed by GO analysis. Interestingly, KEGG analysis revealed these lncRNAs were associated with neurodegenerative disorders such as Alzheimer's disease, Huntington's disease and Parkinson's disease. Four lncRNAs (LOC100507557, LOC101929787, NEAT1, and JAZF1-AS1) were identified as key lncRNAs in AD progression and dysregulated in different distinct regions related to AD. Our study has uncovered several key lncRNAs in AD, which would give novel underlying therapeutic and prognostic targets for AD.

Objective Subclavian steal syndrome results from hemodynamic impairment due to stenosis or occlusion of subclavian artery. Therefore, it is important for subclavian steal syndrome patients to assess hemodynamic status during endovascular therapy. Methods Eleven subclavian steal syndrome patients undergoing endovascular therapy attended this study. Pressure wire was used to measure trans-stenosis pressure difference (ΔP). Digital subtraction angiography, Transcranial Doppler and Electronic sphygmomanometer were introduced to assess stenotic rate, steal grade and inter-arm systolic pressure difference, respectively. Clinical symptoms and restenosis were followed up after endovascular therapy. The associations of ΔP with stenotic rate, inter-arm pressure difference, steal degree, clinic symptoms and restenosis were analyzed in this paper. Results Prior to the therapy, ΔP moderately correlated with stenotic rate (r = 0.757, p = 0.007) and inter-arm pressure difference (r = 0.701, p = 0.016). ΔP was ≥6 mmHg in all patients, and 6–9 mmHg for grade 1 steal and ≥10 mmHg for grade 2 and 3 steals. After the therapy, all patients had technique success, and 10 patients had clinic success, and 1 patient appeared restenosis. ΔP was ≤3 mmHg and steal disappeared in the patients with clinical success. ΔP was 18 mmHg and grade 3 steal still existed in one patient without clinical success. One patient with 1 mmHg of ΔP after therapy appeared restenosis in the follow-up. Conclusion The trans-stenosis pressure difference is closely related to steal degree and clinical symptoms. The measurement of hemodynamic status by pressure wire is very useful to guide endovascular therapy in subclavian steal syndrome patients. However, the restenosis may still occur, even though the hemodynamic impairment is improved.

Background: Abnormal lipid metabolism is considered to be one of main promoters of colorectal cancer (CRC), and intestinal microorganisms may be involved in CRC in patients with abnormal lipid metabolism. Objective: To investigate lipid metabolism in CRC patients and explore the role of intestinal microorganisms in CRC complicated with abnormal lipid metabolism. Methods: Overall, 150 CRC patients in Huzhou Central Hospital from January 2016 to September 2017 were recruited in the present study. Basic patient information and clinical serological indicators were investigated and analyzed. Twenty-one stool samples were collected from patients after receiving informed consent. Next-generation sequencing technology was used to sequence bacterial 16S ribosomal RNA. Bioinformatics analysis was used to profile the microbial composition and screen distinctive bacteria in patients with CRC complicated with abnormal lipid metabolism. Results: Apo B and FFA levels were higher in patients with stage I disease than in patients with other stages. HDL, LDL, Apo B and FFA levels were higher in female patients than in male patients. FFA level was higher in rectal cancer patients than in colon cancer patients. These differences were statistically significant (p

The present research is to investigate the time effect of sinusoidal electromagnetic fields(SEMFs)at different exposure time on the biomechanical properties in rats,and to find a best time for improving biomechanical properties.Forty female SD rats were randomly divided into five groups,i.e.control group,45 min SEMFs group,90 min SEMFs group,180 min SEMFs group,and 270 min SEMFs group.In addition to the control group,other groups were exposed to 50 Hz and 0.1mT magnetic field every day for the corresponding time periods.After eight weeks,bone mineral density(BMD),bone biomechanics,bone tissue morphology,micro-CT and pathological examination were performed.The results showed that there was no abnormal pathological finding in the experimental groups.In the 90 min SEMFs group,BMD,femur maximum load,elastic modulus,yield strength,trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular area(Tb.Ar)percentage were all significantly higher than those in the control group(P0.01),and trabecular separation(Tb.Sp)was significantly lower than that of the control group(P0.01).However,for other experimental groups,some indices showed statistical significance compared to the control group(P0.05),but some did not(P0.05).This study showed that under 50 Hz and 0.1 mT SEMFs,90 min is the best time that can effectively increase bone mineral density,improve the bone tissue microstructure organization and the biomechanical properties.

bObjective:/bTo compare the effects of 50 Hz 1.8 mT sinusoidal magnetic field (SEMF) and 50 Hz 0.6 mT pulsed electromagnetic field(PEMF) on the maturation and mineralization of rat calvaria osteoblasts.bMethods:/bPrimary cultured rat calvarial osteoblasts were divided into 3 groups:blank control group, SEMF group and PEMF group. The rats in SEMT and PEMT groups were treated with 50 Hz 1.8 mT SEMF or 50 Hz 0.6 mT PEMF for 90 min/d, respectively. Western blotting and Real-time RT-PCR were used to detect the protein and mRNA expressions of Collagen-1, bone morphogenetic protein 2 (BMP-2), osterix (OSX) and Runt-associated transcription factor 2(Runx-2). The alkaline phosphatase(ALP) activity was detected by ALP test kits at d6 and d9 after treatment, and by ALP staining using azo coupling at d10 after treatment. The formation of calcium nodules was observed by alizarin red staining.bResults:/bCompared with blank control group, the protein and mRNA expressions of Collagen-1, BMP-2, OSX and Runx-2 in SEMT and PEMT groups were significantly increased (iP/i0.01 oriP/i0.05); while the mRNA expressions of Collagen-1 and BMP-2 in PEMF group were significantly higher than those in SEMF group. After 6 days treatment, the activity of ALP in PEMF group was significantly higher than that in blank control group (iP/i0.05), while such difference was not observed in SEMF group (iP/i0.05); after 9 days treatment, the activities of ALP in both PEMF and SEMP groups were significantly higher than that in blank control group (alliP/i0.05), but the difference between PEMF and SEMF groups was not significant (iP/i0.05). After 10 days treatment, ALP staining was increased in both PEMF and SEMF groups compared with that in blank control group (alliP/i0.01), and the stained area was bigger in PEMF group than that in SEMF group (iP/i0.05). After 12 days treatment, calcium nodules were increased in PEMF and SEMF groups compared with that in blank control group (alliP/i0.01), and more calcium nodules were observed in PEMF group than SEMF group (iP/i0.05).bConclusion:/bBoth 50 Hz 1.8 mT that in SEMF and 50 Hz 0.6 mT PEMF can promote the maturation and mineralization of osteoblasts, and the effect of PEMF is more marked.

Background Chronic hepatitis C (CHC) is a contagious liver disease that results from infection with the hepatitis C virus (HCV). The most serious consequence of CHC is HCV-related hepatocellular carcinoma (HCC). Objective To illustrate the clinical significance of lncRNA HEIH expression in serum and exosomes in the development of HCV-related HCC. Methods Thirty-five CHC, twenty-two HCV-induced cirrhosis and ten HCV-related HCC patients in Huzhou Central Hospital from January 2016 to September 2016 were recruited in the present study. Basic patient information, clinical serological indicators, and clinical imaging data were investigated and analyzed. Serum samples were collected from patients after receiving informed consent. Exosomes were extracted from the serum, and electron microscopy was used to observe the ultrastructure of exosomes. Quantitative PCR was used to detect lncRNA HEIH gene expression in serum and exosomes. Results The changes in the ALT, GGT, HDL, INR, Alb and AFP levels in the patients with HCV-induced cirrhosis and HCV-related HCC were statistically significant. In patients with HCV-related HCC, lncRNA-HEIH expression in serum and exosomes was increased, but the ratio of lncRNA-HEIH expression in serum versus exosomes was decreased compared to patients with CHC.

Studying effects of 50 Hz sinusoidal electromagnetic fields (SEMFs) with different intensities on peak bone mass (PBM) of rats may provide a theoretical basis for application of electromagnetic clinical field. 30 female SD rats, 6 weeks of age, were randomly divided into three groups: the control group, 0.1 mT electromagnetic field group (EMFs) and 0.6 mT EMFs. The EMFs groups were treated for 3 h/day. After 8 weeks, we examined their bone mineral densities (BMD) , measured their bone biomechanical properties, and made serum levels of osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRACP 5b), and histomorphometry. It was found that the BMD (P0.01), maximum mechanical load (P0.01) in the 0.1 mT group were significantly higher than those in the control group, and Yield strength (P0.05), the analyses of serum bone turnover markers and histomorphometric parameters were better than those in the control group (P0.05). However, the 0.6 mT group did not have significantly difference comparing with that in the control group. This study proved that 50 Hz 0.1 mT SEMFs can increased BMD, bone strength, and bone tissue microstructure. Therefore, 50 Hz 0.1 mT SEMFs can improve peak bone mass of rats.