The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.

Re-use of contrast agent during endovascular treatment in patients with contrast agent allergy may lead to severe allergic reaction. For patients with localized stenosis of external iliac artery, endovascular therapy (stenting) is the first choice. Whether patients with severe iliac artery stenosis with contrast allergy can be treated with endovascular therapy is unknowed. A case of iliac artery stenting without contrast agent is reported in this paper. The successful implementation of this operation requires adequate preoperative and intraoperative preparation, and the accurate determination of the stenosis site and the presence or absence of residual stenosis during the operation.

Objective To investigate the effects of 12-lipoxygenase (12-LO) and angiotensin Ⅱ (Ang Ⅱ) on the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs) p21,p27 and p57 related to cell hypertrophy.Methods Mesangial cells were treated with high glucose for 24 hours and 48 hours respectively.12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and Ang Ⅱ were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed high fat diet were received low dose streptozotocin (STZ) to make type 2 diabetes (DN).The rats were divided into normal control group,DN group,DN+Ang Ⅱ type 1 receptor blocker (ARB) group or 12-LO inhibitor (CDC) group.DN+ARB rats were treated by losartan for 6 weeks,and DN+CDC rats were treated for 8 weeks.Urine albumin and protein expressions of p21,p27 and p57 were detected by ELISA and Western blotting respectively.Glomeruli injury and expressions of p21 and p27 were detected by PAS staining and immunohistochemistry respectively.Results High glucose increased p21 and p27 protein expression in mesangial cells significantly compared with the relative control (all P ＜ 0.05),but had no effect on p57.Ang Ⅱ increased p27 protein expression in gloneruli significantly (P ＜ 0.05),but had no effect on p21 and p57 protein expression.12(S)-HETE increased both p21 and p27 protein expression in glomeruli significantly (all P ＜ 0.05),but had no effect on p57 protein expression.Blood glucose,kidney/body weight,urinary protein,and glomerular p21 and p27 protein expressions were increased in DN group (all P ＜ 0.05) compared with those in control group,with little change of p57 protein expression (P ＜ 0.05).Moreover,glomerular hypertrophy and extra cellular matrix accumulation were observed in DN group.However,urine protein,kidney/body weight,renal injury,but not blood glucose,were decreased in DN+ARB group and DN+CDC group compared with DN group respectively (P＜ 0.05).Further DN+CDC rats had decreased both p21 and p27 protein expressions in glomeruli,but DN+ ARB rats only had decreased p27 protein expression (all P ＜ 0.05).Conclusions 12-LO may induce both p21 and p27 protein expression in DN glomeruli,but Ang Ⅱ may induce only p27 expression.

Endovascular aortic repair (EVAR) has been the main treatment means for abdominal aortic aneurysm.It has become an expert consensus that in the case of abdominal aortic aneurysm that is complicated by iliac aneurysm,the preservation of internal iliac artery is necessary because it can prevent the occurrence of gluteal muscle ischemnia,sigmoid ischemia,male sexual dysfunction and other complications.In recent years,with the continuous updating of the endovascular devices it has become possible to retain the internal iliac artery in the performance of EVAR.At present,the reconstruction of internal iliac artery in EVAR includes a variety of techniques,including intraluminal iliac branched device (IBD) technique,sandwich technique,common iliac artery covered-stent bell-bottom (BBT) technique,external iliac artery-internal iliac artery intraluminal shunt technique (reverse chimney technique),and spring coil embolism technique.This article aims to make a summary of all the above mentioned techniques.

Objective To evaluate the feasibility of endovascular aortic repair (EVAR) under local anesthesia without using any contrast agent for abdominal aortic aneurysm in patients with high allergic risk to contrast agent.Methods Under local anesthesia and with no use of any contrast,percutaneous EVAR was performed in a patient with abdominal aortic aneurysm who carried high allergic risk to contrast agent.Results Percutaneous EVAR was successfully accomplished.Postoperative follow-up MRI examination showed that the abdominal aortic aneurysm was completely isolated with no endoleak.The blood flow was unobstructed in the covered stent,and bilateral renal arteries were well visualized.Conclusion For the treatment of abdominal aortic aneurysm in patients who are highly allergic to contrast agent and who have contraindications to general anesthesia,percutaneous EVAR performed under local anesthesia and using no contrast agent is safe and effective.Strict observation of indications and sufficient preoperative evaluation of clinical conditions is the key to ensure a successful operation.

Objective To explore the clinical effectiveness and safety of selective usage of embolic protection device to prevent distal embolization during SilverHawk atherectomy for atherosclerotic femoropo-pliteal artery disease. Methods From Jan 2014 to December 2015, 45 femoropopliteal artery atherosclerot-ic patients were treated with SilverHawk atherectomy and selective embolic protection device (EPD). The indication for EPD was instent restenosis, highly calcified lesion, suspicious of thrombosis, ulcerated le-sion, and single below-the-knee runoff. All cases who met the indication were treated with atherectomy and EPD, and those who did not meet the indication were treated with or without EPD according to the patient's choice. The embolic related complications were analyzed. Results Twenty three out of 45 patients who met the EPD indication were all treated with SilverHawk atherectomy under EPD protection, filter captured deb-ris in 17 patients (73. 9％) of the patients. The other 22 patients who did not meet the indication were di-vided into 2 groups according to the patient's choice of EPD usage, 11 were treated by atherectomy with EPD and 11 without EPD. One case out of 11 unindicated patients without EPD suffered a tibioperoneal trunk embolization and restored with catheter aspiration. For 1/11 (9. 1％) unindicated cases with EPD protec-tion, the filter captured embolization. There was a significant difference of distal embolization rate between the indicated and unindicated patients (χ2 =19. 368,P =0. 000). All filters were retrieved successfully without any distal embolization and any complications except arterial spasm occurred in 2 patients and re-stored well with nitroglycerin. Conclusions It is safe and effective for selective usage of embolic protection device to prevent distal embolization during SilverHawk atherectomy for atherosclerotic femoropopliteal artery disease.

Objective o investigate the clinical efficacy of atherectomy in the treatment of Tosaka class Ⅲ in-stent restenosis in the femoropopliteal artery. Methods From June 2013 to December 2015, 33 restenotic lesions after femoropopliteal artery stenting were retrospectively analyzed by clinical information including technical success rate, incidence of complications, improvement of postoperative symptoms and objective indicators, and target vessel patency. Results To January 2016, twenty-eight cases were followed up. The average follow-up time was 17. 9 months. Five cases were lost. The follow-up rate was 84. 9％. The technical success rate was 100％. The patency rate was 79. 9％ at 6 months and 65. 8％ at 1 year after surgery. Conclusions Atherectomy is safe and effective for treatment of Tosaka classⅢin-stent restenosis in femoropopliteal artery with good short-term and medium-term efficacy.

This study aims to determine whether successful laparoscopic fundoplication for gastroesophageal reflux disease (GERD) can improve the control of hypertension.We conducted an observational study of GERD patients with hypertension.The esophageal and gastroesophageal symptoms of these patients were successfully treated with laparoscopic fundoplication,as measured by the reduced GERD symptoms and proton pump inhibitor consumption.A hypertension control scale was used to classify the use of antihypertensive medications and the quality of blood pressure control before and after anti-reflux surgery.Wilcoxon signed-ranks test was used for the statistical analyses.Seventy GERD patients were included in the analysis and followed up for a mean period of 3.5 ± 1.4 years.Prior to surgery,all participating patients were taking at least one class of antihypertensive medication,and 56 patients (80％) had intermittently high blood pressure.After surgery,the mean number of antihypertensive medication classes per patient was significantly reduced from 1.61 ± 0.77 pre-procedure to 1.27 ± 0.88 post-procedure (P ＜ 0.001).The blood pressure of 48 of the 56 cases (86％) with preoperative intermittent high blood pressure returned to normal post procedure.A total of 50 patients (71％) recorded improvements on the hypertension control scale,with the overall mean score decreasing from 3.1 ± 1.0 preprocedure to 1.4 ± 1.0 post-procedure (P ＜ 0.001).Therefore,successful laparoscopic fundoplication may result in better blood pressure control in some hypertensive GERD patients.This result suggests a possible connection between gastroesophageal reflux and hypertension.