The aim of this paper is to report the synthesis of the mPEG-PCL-g-PEI copolymers as small interfering RNA (siRNA) delivery vector, and exploration of the siRNA delivery potential of mPEG-PCL-g-PEI in vitro. The diblock copolymers mPEG-PCL-OH was prepared through the ring-opening polymerization. Then, the hydroxyl terminal (-OH) of mPEG-PCL-OH was chemically converted into the carboxy (-COOH) and N-hydroxysuccinimide (NHS) in turn to prepare mPEG-PCL-NHS. The branched PEI was reacted with mPEG-PCL-NHS to synthesize the ternary copolymers mPEG-PCL-g-PEI. The structure of mPEG-PCL-g-PEI copolymers was characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The mPEG-PCL-g-PEI/siRNA nanoparticles were prepared by complex coacervation, and the nanoparticles size and zeta potential were determined, separately. The cytotoxicities of mPEG-PCL-g-PEI/siRNA nanoparticles and PEI/siRNA nanoparticles were compared through cells MTT assays in vitro. The inhibition efficiencies of firefly luciferase gene expression by mPEG-PCL-g-PEI/ siRNA nanoparticle at various N/P ratios were investigated through cell transfection in vitro. The experimental results suggested that the ternary (mPEG5k-PCL(1.2k))1.4-g-PEI(10k) copolymers were successfully synthesized. (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k) could condense siRNA into nanoparticles (50-200 nm) with positive zeta potential. MTT assay results showed that the cytotoxicity of (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k)/siRNA nanoparticles was significantly lower than that of PEI(10k)/siRNA nanoparticles (P < 0.05). The expression of firefly luciferase gene could be significantly down-regulated at a range of N/P ratio from 50 to 150 (P < 0.01), and maximally inhibited at the N/P ratio of 125. The mPEG-PCL-g-PEI polymers could delivery siRNA into cells to inhibit the expression of target gene with very low cytotoxicity, which suggested that mPEG-PCL-g-PEI could serve as a new type of siRNA delivery vector.

Traditional treatments for malignant tumor are far from meeting the clinical demands.Recently,research on anti-tumor targeted drugs has made a significant breakthrough,which brings new hope for the treatment of malignant tumor.Anti-tumor targe-ted drugs can specifically target malignant tumor and directly in-hibit the growth of tumor cells,showing no toxicity to the normal tissues and organs.Herein we reviewed the research progress of small molecular targeted drugs and antibody targeting new drugs.

RNA interference (RNAi) is a newly developed technology. It is the different levels of gene silencing induced by specific degradation of targeted genes in vivo, and both exogenous and endogenous double-stranded RNAs could induce the specific degradation. RNAi has been applied in tumor therapy, viral infection, hepatitis B and many other diseases. siRNA is the effector molecule which induces the RNAi in vivo. But naked siRNA is easily degradated by RNases in vivo, and the half-life is short. Meanwhile, the transfection efficiency of the naked siRNA is comparatively low. So the naked siRNA needs the help of vectors to penetrate the cell membrane and take action. Viral vectors have the potential immunogenicity and mutagenicity in gene therapy. Therefore, non-viral vectors are drawing more and more attention. The latest development of the non-viral vectors is summarized in this review.

Doxorubicin loaded micelles were prepared by film-hydration method using stearyl sulfadiazine (SA-SD) which is pH sensitive, methoxy (polyethylene glycol)-2000-1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (mPEG-DOPE) and transactivator of transcription (TAT) peptide conjugated PEG-DOPE. Mean diameter of the pH-sensitive micelles was about 20 nm with a (99.1 +/- 2.1) % drug entrapment efficiency at pH 7.4. Flow cytometry studies revealed that the simple TAT micelles was taken up rapidly at the same level at pH 6.8 and pH 7.4. However, the pH-sensitive micelles entered the tumor cell less at pH 7.4 and significantly increase at pH 6.8. After 1 h incubation at pH 6.8, the amount of the pH-sensitive micelles taken up by cancer cell 4T1 was almost similar to simple TAT micelles. The confocal microscopy indicated that the pH-sensitive micelles entered the 4T1 cells at pH 6.8 more than at pH 7.4. It was indicated that the pH-sensitive micelles could shield TAT peptide at normal pH 7.4 and deshield it at pH 6.8. Hence, TAT peptides lead the drug-loaded micelles into the tumor cells and killed them selectively. The pH-sensitive micelle may provide a novel strategy for design of cancer targeting drug delivery system.

Objective To establish a simple and efficient method for developing a keloid model in nude mice with human keloid-derived fibroblasts.Methods Twenty-seven female BALB/c nude mice were randomly divided into five groups with 5,5,5,8 and 4 mice in group A,B,C,D and E respectively.The mice in group A,B and C were inoculated with 0.1 ml of suspension containing human keloid-derived fibroblasts at concentrations of 1.0 × 104,3.0 × 104 and 5.0 × 104 per microliter Matrigel,respectively,at the right axillary fossa.The tumors that formed in one mouse in group C were taken out,and cut into several parts measuring 5 mm × 5 mm × 5 mm in size,which were then subcutaneously transplanted into the right axillary fossa of mice in group D.The mice in group E were subcutaneously injected with 100 μl of Matrigel and served as the control group.The formation of tumor in mice was observed by naked eyes,and the size of tumors was measured until day 30 after tumor formation in group A,B and C as well as after tumor transplantation in group D.Mice were sacrificed on day 30 after tumor formation,and histopathologic examination was performed to analyze histological features of transplanted tumors and pathological changes in visceral organs such as heart,liver,spleen,lung and kidney.Results The tumor formation rate was consistently 100％ in group A,B and C,and the time required for tumor formation was (90.20 ± 3.96),(61.00 ± 2.92) and (39.60 ± 3.20) days in group A,B and C respectively.There was a significant difference in tumor volume on the 30th day after tumor formation between group A,B and C ((288.34 ± 25.29) vs.(1 370.63 ± 105.24) vs.(1 940.98 ± 184.37) mm3,F =138.74,P ＜ 0.05).The size of implanted tumor mass in group D firstly increased,then gradually decreased,but began to continuously increase since the 14~ day,and tumor finally formed in 7 out of 8 mice.There was no evidence of tumor formation in group E.Histopathologic examination showed uniform histological manifestations,which were similar to those of human scar,in tumor tissues from mice in group A,B,C and D.Neither pathological changes nor metastases were observed in visceral organs of these mice.Conclusion Keloid-bearing nude mouse model can be established by subcutaneous inoculation with human keloidderived fibroblasts,or by subcutaneous transplantation of tumor masses of a certain size that have formed in nude mice.

Objective To evaluate high resolution manometry in the diagnosis of hiatal hernia.Methods Clinical data were reviewed on 20 patients suffering from gastroesophageal reflux who had laparoscopic Toupet fundoplication for preoperative tentative diagnosis of hiatal hernia.Preoperative diagnosis of hiatal hernia was made collectively by endoscopy,X-ray examination,24 hour esophageal pH monitoring and high resolution manometry before surgery.Results Preoperative diagnosis of hiatal hernia was made in 3 patients by X-ray examination,in 9 patients by high resolution manometry.11 patients were finally diagnosed with hiatat hernia intraoperatively.X ray was consistent with intraoperative diagnosis in 27％ cases.Intraoperative and endoscopic diagnoses were 55％.High resolution manometry and intraoperative diagnoses were consistent in 82％.Lower esophageal sphincter length was (1.92 ± 0.38) cm in hiatal hernia group and (2.10 ± 0.92) cm in non-hiatal hernia group (t =0.60,P ＞ 0.05),lower esophageal sphincter pressure (respiratory min) was (0.64 ±0.55) kPa in hiatal hernia group and (1.31 ± 1.07) kPa in nonhiatal hernia group(t =1.80,P ＞ 0.05),and lower esophageal sphincter pressure (respiratory mean) was (1.43 ±0.92) kPa in hiatal hernia group and (2.57 ± 1.33) kPa in non-hiatal hernia group(t =2.26,P ＜0.05).The reflux parameters,including the percent total time pH ＜ 4,and DeMeester score,were significantly greater in hiatal hernia group than in non-hiatal hernia group (all P ＜ 0.05).Conclusions Hiatal hernia patients are with poor esophageal antireflux competency and severe reflux.High resolution manometry is more valuable in the diagnosis of hiatal hernia than endoscopy or X-ray examination.

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 investigate the safety and feasibility of carotid endarterectomy (CEA) combined with carotid artery stent angioplasty (CASA) in treating tandem stenosis of carotid artery. Methods The clinical data of 9 patients with tandem stenosis of carotid artery, who were treated at authors' hospital during the period from January 2013 to October 2014, were retrospectively analyzed. The patients included 7 males and 2 females, with a mean age of (66.0 ±4.2) years. The disease course ranged from 2 months to 36 months, with a mean of 7 months. Clinically, all patients had cerebral ischemia symptoms. Transient ischemia attack was seen in 5 patients and history of cerebral infarction was present in 2 patients. Coronary artery disease was found in 2 patients, hypertension in 6 patients and lower limb ischemia in one patient. After receiving adequate antiplatelet therapy, CEA and CASA were carried out in all patients. Results The technical success rate was 100%, postoperative residual stenosis was less than 30%, no death occurred in perioperative period. After the treatment, the clinical symptoms were improved in all 9 patients;no new stroke or cerebral hemorrhage occurred. After the treatment, 2 patients developed cerebral hyperperfusion-related symptoms such as headache and dizziness, which were much relieved at the time of discharge. The patients were followed up for 4-19 months, with a mean of (10.5±6.2) months. No recurrence of symptoms was observed . In one patient , transcranial Doppler ultrasound performed at 6 months after treatment showed that the carotid artery became moderate restenosis (50%-70%). No death occurred. Conclusion For the treatment of tandem stenosis of carotid artery, CEA combined with CASA is safe and effective, although larger sample and long-term follow-up studies are still needed to further confirm the effect.