Targeted drug delivery can significantly increase the concentration of the drug in treatment site, and decrease the dosage of drugs, cost of treatment and the drug's adverse effects on the body. So targeted drug delivery is the hotspot of recent studies. This paper reviews the development of targeted drug delivery research in recent years, including three areas: passive targeting, active targeting, and physical and chemical targeting.

ObjecfiveTo compare the sensitivity of diffusion weighted imaging(DWI)with dynamic contrast enhanced(DeE)MRI for the detection of small breast caJlcers and to evaluate the clinical value of DWI.MethodsForty-eight patients with benign(n=25)and malignant(n=45)small breast lesions(≤2 cm)proved by pathology underwent DWI and DCE MRI.The DCE MRI was performed using FLASH sequence and the time-signal intensity chive was drawn.The DWl was performed using GRAPPAEPI sequence with different b values(800,1000 s/mm2) and the ADC values of lesions were measured.The sensitivity and specificity of DWI for the detection of small breast cancers were compared with DCE MRI. ResultsForty of 45 small breast cancers and 19 of 25 small benign breast lesions were corrlectly diagnosed using DCE MRI.The sensitivity and positive predictive value of TIC were 88.9%(40/45)and 87.0%(40/46).With b values of 800 s/mm2 and 1000 s/mm2,the avemge ADC values of small breast cancers were(1.153±0.192)× 10-3 and(1.079±0.186)× 10-3 mm2/s,while those of benign ones were (1.473±0.252)×10-3 and(1.419±0.255)×10-3 mm2/s,respeetively. There was no significant difference for the ADC values with different b values in the same group(P＞0.05),while there was a signiticant difference between the malignant and the benign lesions(P＜0.05)Thirty-nine of 45 small breast cancers and 19 of 25 small benign breast lesions were correctly diagnosed using DWI with b value of 1000see/mm2.Both the sensitivity and positive predictive value of diagnosis were 86.7%(39/45).The abilities of DWI and DCE MRI for the diagnosis of small breast cancers werle the same. The sensitivity(93.3%)and positive predictive value(91.3%)were improved with the combination of DCE MRI and DWI. Conclusion DWI has a high sensitivity for the detection of small breast cancers,the ADC value can provide valuable information in the differential diagnosis.

Objective To investigate the diagnostic value of conventional and dynamic gadolinium-enhanced T1-weighted (T1W) MRI in benign and malignant endometrial polypoid lesions. The pathologic basis of MRI features was also evaluated. Methods The conventional and dynamic contrast enhanced MRI features in 48 cases with clinicopathologically-proved endometrial polypoid lesions were retrospectively analyzed, including 26 cases with malignant tumors (23 eases with endometrial carcinoma and 3 cases with endometrial sarcoma) and 22 cases with benign polypoid lesions (12 cases with endothehal polyps and 10 cases with submucons leiomyomas). The occurrence probability of central fibrous core, intratumoral cysts and intact junctional zone were evaluated by Fisher's exact test. Results Benign and malignant endometrial polypoid lesions had specific characteristics on MRL Endometrial carcinomas usually appeared as homogeneous intermediate or slightly high signal-intensity masses on T2-weighted images, and relatively homogeneous hypedense masses on contrast-enhanced images with myometrial invasion (P < 0.05). An irregular central fthrous core and small non-enhanced intratumoral cysts were seen more frequently in endometrial polyps (P < 0.05) than others. All 3 cases with uterine sarcomas showed obviously inhomageneous intensity on T2WI and demonstrated areas of early and persistent marked enhancement.Submucous leiomyomas demonstrated isodense or slightly low-density masses with defined outline on T2 WI and the endomerium was displaced. The diagnostic sensitivity, specificity and accuracy of malignant polypoid masses were 92.3% (24/26), 83.3% (20/24) and 95.8% (46/48) respectively. Conclusion Conventional and dynamic contrast-enhanced MRI are valuable in characterizing the benign and malignant endometrial polypoid lesions.

ObjectiveTo investigate the feasibility of examining aortic pulse wave velocity (PWV),aortic distensibility (AD) and brachial artery flow-mediated dilation (FMD) by means of highresolution 3.0 T MRI.MethodsA total of 32 healthy volunteers underwent high-resolution MRI to assess aortic PWV,and AD in ascending aorta (AA),proximal descending aorta (DA),distal descending aorta (DDA) and FMD of the brachial artery with repeat examination performed in 1-2 hours.PWV was evaluated by 2D Phase Contrast (PC) velocity-encoded MRI with a 4.7-7.8 ms temporal resolution.Fiesta-cine MRI was used to assess AD and FMD with a 18.75-31.25 ms temporal resolution.The image quality of these two scans was scored and the agreement between them was tested with Kappa analysis.The reproducibility of the results between repeated measurements of PWV,AA-AD,DA-AD,DDA-AD and FMD was assessed with intra-class correlation coefficient (ICC) analysis.The method of Bland-Altman plot was used to assess the agreement between results of repeated studies.Results Each examination including PWV,AD and FMD were completed in about half an hour.The image quality between repeated scans showed good agreement ( Kappa value 0.776 ) with the score of ( 3.53 ± 0.62 ) and ( 3.41 ± 0.67 ) respectively.Reproducibility between repeated measurements was high for aortic PWV [ (4.33 ± 0.88 ) vs ( 4.36 ±0.88) m/s],AA-AD [(8.60±3.11) × 10-3 vs (8.59 ± 3.10) × l0-3/mm Hg(1 mm Hg =0.133 kPa) ],DA-AD[ (6.95 ±2.44) × 10-3 vs (6.95 ±2.42) × 10-3/mm Hg],DDA [(10.54 ±2.91) ×l0-3 vs (10.55 ±2.90) × 10-3/mm Hg] and FMD [(24.94 ± 12.55)％ vs (24.92 ±1 2.38 ) ％ ].ICC were 0.95,0.97,0.99,0.98 and 0.94,P ＜ 0.01.Excellent agreement between repeated measurements was found for aortic PWV [ confidence interval (CI) between - 0.55 and 0.50 ],AA-AD ( CI between - 0.11 and 0.12 ),DA-AD ( CI between - 0.08 and 0.08 ),DDA-AD ( CI between - 0.23 and 0.21 ) and FMD (CI between - 1.46 and 1.51 ).The maximum difference percentage in minimum average for aortic PWV,AA-AD,DA-AD,DDA-AD and FMD was 38.53％,9.65％,3.86％,5.68％,42.37％,respectively,all less than 50％.Conclusion Comprehensive assessment of aortic compliance and brachial endothelial function can be achieved using 3.0 T high-resolution MRI with excellent reproducibility and within a reasonable amount of time.

Objective The purpose of this study is to assess the value of multi-slice spiral CT(MSCT)in the preoperative evaluation of living renal donor as a all in one modality.Methods Thirty-six potential living renal donors underwent the examination using a GE light VCT scanner.Informed consent was obtained from all participants.The plain scan,early arterial phase,late arterial phase and excretory phase scans are performed in the former 25 donors(injection rate 5 ml/s,total volume 100 ml,tube tension 120 kV).While in the later 11 donors(2 ml/s 40 ml+4 ml/s 60 ml),the scanning protocol included the plain scan(100 kV),vascular phase and excretory phase scans(100 kV).The excretory phase data were used in the reconstruction of CT urography in both groups.All images were reviewed by one radiologist and one urologist,and the findings of MSCT were compared with intraoperative findings for 33 donors,to investigate the utilities of MSCT in assessing renal vascularity,urinary tract and lesions of renal parenchyma.When discrepancies are found between the two reviewers,consensus was obtained via discussion.Au data was statiscally processed with SPSS for Windows.Results MSCT angiography is in accordance with intraoperative findings in demonstrating the anatomy of renal arteries and renal vein trunk,accesary arteries,early branching of renal artery.The findings from CTA are highly in accordance with the intraoperative findings,which facilitate intraoperative ligation and reduce relevant complications.CTU demonstrates the anatomy of urinary tract in good agreement with the intraoperative findings.The image quality of 3D vascularity and CTU between the two groups.scored 4.4±1.2 vs 4.2±1.3 and 4.6±0.8 vs 4.4±0.9 respectively,no statistical between-groups difference was found(Z=-0.89,-0.47,P＞0.05).Conclusion MSCT multiphase scanning combined with CTA and CTU play a important role in the evaluation of living renal donor,which preoperatively provide detailed information of renal vascularity,urinary tract and renal parenchyma as a all-in-one modality.

Objective To investigate the chondrogenic feasibility of the human umbilical cord derived mesenchymal stem cells (hUCMSCs)as cartilage tissue engineering seed cells ,type Ⅱ collagen composite glycosaminoglycan scaffold as the cellular carrier and cell‐scaffold complex .Methods The type Ⅱ collagen composite glycosaminoglycan scaffolds was prepared .The pore diameter , porosity and hydrophilia of scaffold materials were observed and measured by electronic microscope .The corresponding histological analysis on the scaffold materials was performed .hUCMSCs of P3 generation were cultured and identified .The hUCMSCs suspen‐sion was inoculated in the type Ⅱ collagen composite glycosaminoglycan scaffold for conducting culture without adding inducer .The samples were taken out after 3 weeks and performed the toluidine blue and safranin O staining ,type Ⅱ collagen immunohistochemi‐cal staining and SEM scanning .Results hUCMSCs of P3 generation highly expressed the mesenchymal cell marker CD29 and CD105 ,while hardly expressed endothelial cells of CD34 and hematopoietic cell markers .The type Ⅱ collagen composite glycosami‐noglycan scaffold presented white porous foam like ,the porosity was (91 .8 ± 2 .17)% ,the average pore diameter was 110‐230 μm , which was homogeneously distributed and had interpenetration .The scaffold showed good hydrophilicity with the water absorption expansion rate of (213 .71 ± 1 .31)% .The scaffold staining of toluidine blue ,safranin O and type Ⅱ collagen was positive .The car‐tilage‐like tissues were observed ,and gradually increased in the surface of cell‐scaffold complex along with culture ,which were posi‐tive in Toluidine blue ,safranin O and type Ⅱ collagen staining ,the electronic microscopic observation displayed that the cells were actively proliferated in the scaffold ,closely adhered with the materials ,the cartilage‐like cells and a large number of peripheral colla‐gen fibers with zigzag connection could be seen .Conclusion Compositing hUCMSCs and type Ⅱ collagen composite glycosamin‐oglycan scaffold could construct tissue‐engineering cartilage in vitro without induction ,which lays a certain experimental foundation for the repair of cartilage damage .

Objective:To explore the effect of esophageal squamous cell carcinoma-related long non-coding RNA (lncRNA) ESCCAL-1 on the polarization of THP-1 cells-derived macrophages.Methods:The esophageal cancer cell line KYSE450 was divided into 5 groups: KYSE450 group (normal KYSE450 cells), shRNA-ESCCAL-1 group (infected with knockout ESCCAL-1 lentivirus), shRNA-NC group (infected with interference control lentivirus), OE-ESCCAL-1 group (infected with overexpressing ESCCAL-1 lentivirus) and OE-NC group (infected with overexpressed control lentivirus). The expression of ESCCAL-1 was detected by real-time quantitative polymerase chain reaction (qRT-PCR). After co-culture of cells in each group with THP-1 cells-derived macrophages, flow cytometry was used to detect the expressions of THP-1 cells-derived macrophages M1 polarization markers HLA-DR, iNOS, CD86 and M2 polarization markers Arg-1, CD163, CD206, and inflammatory cytokines.Results:After THP-1 cells were stimulated with 100 ng/ml phorbol ester for 48 hours, the cells grew adherently, and the expression levels of CD11b and CD36 increased, indicating that THP-1 cells were successfully differentiated into macrophages. After THP-1 cells-derived macrophages were co-cultured with esophageal cancer KYSE450 cell line treated differently for 24 hours, there were no significant differences in the expressions of M1 polarization markers HLA-DR, iNOS and CD86 between shRNA-ESCCAL-1 group and shRNA-NC group or between OE-ESCCAL-1 group and OE-NC group (all P > 0.05). Compared with shRNA-NC group, the expressions of M2 polarization markers Arg-1, CD163 and CD206 in shRNA-ESCCAL-1 group decreased [8.54±0.29 vs. 11.83±0.69, 12.0±0.3 vs. 24.5±0.8, 2.05±0.23 vs. 14.54±1.10], and the differences were statistically significant ( t values were 7.636, 27.38 and 19.31, all P < 0.01); compared with the OE-NC group, the expressions of M2 polarization marker Arg-1, CD163 and CD206 in OE-ESCCAL-1 group increased [32.60±1.14 vs. 14.20±0.20, 43.7±1.5 vs. 25.1±1.2, 35.8±0.7 vs. 13.6±0.6], and the differences were statistically significant ( t values were -27.58, -17.24 and -43.98, all P < 0.01). Compared with shRNA-NC group, the expression level of interferon-γ in shRNA-ESCCAL-1 group decreased [(6.3±1.5) pg/ml vs. (20.0±2.6) pg/ml, t = 7.75, P = 0.001]; compared with OE-NC group, the expression level of interleukin-1RA in OE-ESCCAL-1 group increased [(3 167±306) pg/ml vs. (467±176) pg/ml, t = -13.27, P < 0.01]. Conclusions:Esophageal squamous cell carcinoma-related lncRNA ESCCAL-1 can promote the M2 polarization of macrophages.

Objective To identify the reasons and treatment strategies of epidural fluid collection (EFC) secondary to cranioplasty in patients with traumatic brain injury after decompressive craniectomy.Methods From June 2013 to July 2017,a retrospective analysis was performed on clinical data of 150 patients with traumatic brain injury after decompressive craniectomy in our hospital.A total of 47 patients experienced EFC following cranioplasty and 103 not.Risk factors of EFC after cranioplasty were analyzed by multiple factor Logistic regression.Results For the 47 EFC patients,32 patients had no obvious clinical symptoms and EFC was absorbed gradually through conservative therapy;15 patients had clinical symptoms,such as mental deterioration,headache,or limb weakness.EFC disappeared through vacuation in 4 patients and subcutaneous drainage in 11.The proportions of patients with skull defect＞80 cm2,dural defect and dural calcification in patients with EFC were significantly higher as compared with those without EFC (P＜0.05).Multiple factor Logistic regression analysis showed that skull defect＞80 cm2 and dural mater calcification were independent risk factors for EFC after cranioplasty.Conclusions Patients with large skull defect＞80 cm2 and dural calcification are prone to have EFC after cranioplasty.Careful evaluation of imaging data,good surgical skills and strengthening postoperative management can reduce incidence of EFC after cranioplasty.

Objective To study the clinical features of hepatic pseudolymphoma.Methods A retrospective study was conducted on 19 patients with hepatic pseudolymphoma who were diagnosed and treated at Zhongshan Hospital in Shanghai from June 2013 to December 2017.Eighteen patients were females and one was a male.The mean age was (55±9) years,range 36 to 68 years.This study mainly analyzed the imaging features,treatment and postoperative results.Results All patients were diagnosed accidentally,and 78.9％ patients did not exhibit any evidence of hepatic B viral infection.A monofocal lesion was found in 14 patients and multifocal lesions in 5 patients.Surgical treatment was performed in all the patients.The lesion size was (1.1±0.4) cm (range 0.5～2.4 cm).Ultrasound revealed hypo-or slightly hypo-echogenicity.On MRI,diffusion weighted imaging showed slight hyperintensity or hyperintensity,all lesions manifested as homogeneous and slightly hyperintensity on T2WI and hypointensity on T1WI.Dynamic enhancement pattern,wash in and wash out,degressive and persistent enhancement were observed in 16(55.2％),12(41.4％),and 1 (3.4％) patients,respectively.More than 70％ of lesions were diagnosed as malignant tumors on preoperative imaging.During a follow-up of 6 ～ 44 months (median:19 months),no patient developed metastasis or recurrence.Conclusions Hepatic pseudolymphoma commonly occurred in women with a small sized lesion.Due to the lack of specific clinical manifestations and imaging findings,preoperative diagnosis was difficult.Surgical resection is still the most optimal treatment.The patients usually have favorable prognosis.

Objective: To predict the efficacy of endoscopic tissue adhesives in the treatment of gastric varices in patients with liver cirrhosis by Nomogram model. Methods: From August 2014 to September 2017, 158 patients with liver cirrhosis caused esophagogastric variceal bleeding and received endoscopic tissue adhesives treatment at Zhongshan Hospital, Fudan University were collected. All patients were followed for 12 months. The primary outcome was rebleeding. The factors of rebleeding after endoscopic treatment of esophagogastric varices were analyzed. Nomogram prognostic model was developed and compared with Child-Pugh grading, computed tomography angiography (CTA) and hepatic venous pressure gradient (HVPG) in prognostic accuracy in rebleeding after endoscopic treatment in liver cirrhosis caused esophagogastric varices. Univariate and multivaricate Cox regression analysis, Kaplan-Meier curve and log-rank test were performed for statistical analysis. Results: During the follow-up, rebleading occurred in 18 cases (11.4%), 37 cases (23.4%) and 49 cases (31.0%) at 2, 6, and 12 months after endoscopic treatment. The results of univariate Cox regression analysis showed the risk factors of rebleeding after endoscopic treatment of gastric varices included gender, alcoholic liver cirrhosis, diabetes mellitus, Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence vs. absence) HVPG (<16 mmHg vs. ≥16 mmHg, 1 mmHg = 0.133 kPa), extensive portal embolism, esophageal varices, type 2 gastric varices, injection points of tissue adhesive (≤3 points vs. > 3 points), injection volume of tissue adhesive (≤ 3 mL vs. > 3 mL) (hazard ratio (HR)=0.575, 2.018, 1.562, 3.433, 2.945, 1.859, 2.743, 0.324, 1.840, 1.477, and 1.716; 95% confidence interval (CI) 0.305 to 1.084, 0.902 to 4.514, 1.753 to 6.724, 1.663 to 5.217, 1.012 to 3.415, 0.852 to 8.830, 0.079 to 1.335, 1.012 to 3.317, 0.839 to 2.602, and 0.935 to 3.152; all P<0.2). The results of multivariate Cox regression analysis indicated that Child-Pugh grade, extraluminal vessels by CTA, and HVPG (HR = 2.095, 95% CI 1.099 to 3.995, P = 0.025) were all independent risk factors of rebleeding after endoscopic treatment of gastric varices (HR=2.665, 2.886, and 2.095; 95% CI 1.339 to 5.300, 1.580 to 5.271, and 1.099 to 3.995; all P<0.05). Kaplan-Meier curves showed that Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence or absent) and HVPG (<16 mmHg vs. ≥16 mmHg) could effectively predict cumulative non-rebleeding rate in one year after endoscopic treatment of gastric varices, and the differences were statistically significant (all P<0.05). Receiver operataring characteristic curve analysis demonstrated that the predictive value of the model combined with Child-Pugh grade, extraluminal vessels on CTA and HVPG was higher than that of Child-Pugh grade and HVPG (AUC=0.746, 0.673 and 0.585; 95% CI 0.662 to 0.829, 0.583 to 0.762, and 0.486 to 0.683; P<0.01, P=0.001 and P=0.089, respectively). Patients were divided into low, medium, and high-risk groups according to the 25th and 75th percentiles of the Nomogram score. The results showed that Nomogram model could effectively distinguish high-risk groups of rebleeding after endoscopic treatment of gastric varices, and the difference was statistically significant (P <0.01). Conclusions Extraluminal vessels on CTA, HVPG and Child-Pugh grade are independent prognostic evaluation indexes of rebleeding after endoscopic treatment of gastric varices. The predictive accuracy of Nomogram model based on these three prognostic factors may be better than Child-Pugh grade and HVPG.