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Shubin Wang,1,* Juan An,2,* Weiwei Dong,3,* Xin Wang,4 Jianqiu Sheng,4 Yan Jia,4 Yuqi He,4 Xianzong Ma,4 Jiheng Wang,4 Dedong Yu,1 Xiuqin Jia,1 Bingyu Wang,5 Wenbo Yu,5 Kejia Liu,5 Yuanyuan Zhao,6 Yun Wu,1 Wei Zhu,1 Yuanming Pan1,4,6 1Department of Oncology, Baotou City Central Hospital, Baotou 014040, People’s Republic of China; 2Department of Basic Research Medical Sciences, Qinghai University, Xining 810001, People’s Republic of China; 3Department of Oncology, General Hospital of Chinese People’s Liberation Army, Beijing 100085, People’s Republic of China; 4Department of Gastroenterology, The 7th Medical Center of Chinese PLA General Hospital, Beijing 100700, People’s Republic of China; 5Yidu Cloud (Beijing) Technology Co. Ltd 8F, Health Work, Beijing 100083, People’s Republic of China; 6National Center for Nanoscience and Technology, Zhongguancun, Beijing 100190, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanming PanNational Center for Nanoscience and Technology, Zhongguancun, Beijing 100190, People’s Republic of ChinaTel +86-10-6406-9831Fax +86-10-6401-2266Email panym@nanoctr.cnWei ZhuDepartment of Oncology, Baotou City Central Hospital, Baotou, Inner Mongolia 01404, People’s Republic of ChinaTel +86-472-6955473Fax +86-472-6955708Email 18686111667@163.comIntroduction: Glioma is the primary malignant brain tumor with poor prognosis. Berberine (BBR) was the potential drug for anti-tumor in glioma cells. Based on its limitation of poor aqueous solubility and instability, little information of BBR nanoparticles is reported in glioma.Methods: Different solutions including 5% glucose, 1*PBS, ddH2O, 0.9% NaCl, cell culture medium were selected, and only 5% glucose and ddH2O exhibited BBR-related nanoparticles. After heating for a longer time or adding a higher concentration of glucose solution, BBR nanoparticles were detected by TEM analysis. The uptake of BBR-Glu or BBR-Water nanoparticles were detected by immunofluorescence analysis for BBR autofluorescence. Cell viability was measured by MTT assay and Western blotting analysis. Apoptosis was performed with flow cytometric analysis and was detected by cleaved caspase-3 immuno-fluorescent staining. Cell cycle was used by flow cytometric analysis. Cytoskeleton was observed by confocal analysis using the neuron specific Class III ß-tubulin and ß-tubulin antibodies. Mitochondrial-related proteins were detected by Western blotting analyses and mito-tracker staining in live cells. Mitochondrion structures were observed by TEM analysis. ROS generation and ATP production were detected by related commercial kits. The tracking of BBR-Glu or BBR-Water nanoparticles into blood–brain barrier was observed in primary tumor-bearing models. The fluorescence of BBR was detected by confocal analyses in brains and gliomas.Results: BBR-Glu nanoparticles became more homogenized and smaller with dose- and time-dependent manners. BBR-Glu nanoparticles were easily absorbed in glioma cells. The IC50 of BBR-Glu in U87 and U251 was far lower than that of BBR-Water. BBR-Glu performed better cytotoxicity, with higher G2/M phase arrest, decreased cell viability by targeting mitochondrion. In primary U87 glioma-bearing mice, BBR-Glu exhibited better imaging in brains and gliomas, indicating that more BBR moved across the blood–brain tumor barrier.Discussion: BBR-Glu nanoparticles have better solubility and stability, providing a promising strategy in glioma precision treatment.Keywords: berberine, glioma, glucose-nanocarrier, nanoparticles, mitochondria

Additional file 1. Figure 1-6 The small-intestine stimulation enhanced computer tomography (CT) examination revealed an unevenly thickened and strengthened wall of the sigmoid colon, splenomegaly, and portal hypertension. Figure 7-9. Colonoscopy revealed two ulcers in the small intestinal mucosa, multiple ulcers and erosions throughout the colon, and normal mucosa between the ulcers. Figure 10-11. The specimen of the diseased ileum (approximately 10 cm) after the enterectomy.Figure 12. Postoperative histopathological examination showed inflammation of the arterioles of the intestinal wall, obvious stenosis or even occlusion of the arterial vascular lumen, proliferation of arterial smooth muscle and destruction of elastic fibres. Figure 13-14. Re-examination of the electronic colonoscopy after surgery showed no signs of recurrence. Figure 15-16. Re-examination of the CT after surgery showed splenomegaly still existed. Figure 17. The patients underwent abdomen CT revealed that her renal vessels were not involved.

ObjectiveTo investigate the clinical effect and safety of balloon-assisted enteroscopy combined with endoscopic retrograde cholangiopancreatography (ERCP) in patients with altered gastrointestinal anatomy. MethodsA total of 12 patients who were admitted to General Hospital of Beijing Military Region from April 2016 to October 2017 and underwent balloon-assisted ERCP after surgical alteration of gastrointestinal anatomy were enrolled, among whom 4 underwent choledochoenterostomy and 8 underwent pancreaticoduodenectomy. Double-balloon enteroscopy was performed for 4 patients and single-balloon enteroscopy was performed for 8 patients. A retrospective analysis was performed for treatment outcome, complications, and prognosis. ResultsA total of 10 patients underwent balloon-assisted ERCP successfully, resulting in an overall success rate of 83.3%, and among these patients, 2 had simple anastomotic stenosis and 8 had anastomotic stenosis and intrahepatic bile duct stones. Among the two patients who did not complete ERCP, one had severe anastomotic stenosis which prevented the guide wire from entering the bile duct, and the other patient had a small angle of R-Y intestinal anastomosis which prevented the lens and the cannula from entering the afferent loop. After surgery, one patient experienced jaundice and one experienced perforation of the gastrointestinal tract, resulting in an incidence rate of complications of 16.7%, and both patients were cured after conservative treatment. ConclusionBalloon-assisted ERCP has good safety and a marked clinical effect with unique complications, as well as a lower success rate than conventional ERCP.