Doxorubicin-loaded fluorescent carbon dots with PEI passivation as a drug delivery system for cancer therapy.

In this work, we reported a novel and effective cancer treatment strategy by fabricating carbon dot (CD)-polyethylenimine (PEI)-doxorubicin (DOX) antitumor drug complexes from a combination of PEI-passivated CDs (CD-PEI) and DOX. CD-PEI was synthesized by the one-step microwave hydrothermal carbonization of a mixture of glycerol and PEI-25k, enabling simultaneous synthesis and surface passivation of CDs. DOX was loaded onto CD-PEI by electrostatic interactions. The results show that this system not only improves selective drug release but also prolongs the drug release time and improves the killing effect on tumors. Compared with free DOX, the CD-PEI-DOX complex has a stronger killing effect on liver cancer cells (MHCC-97L and Hep3B cells) but a very low killing effect on normal liver cells (L02). Studies have also confirmed that compared with DOX alone, CD-PEI-DOX nanoparticles can effectively inhibit tumors because of the larger amount of drugs localized in tumor cells and the higher apoptosis rate of MHCC-97L cells. In vivo experiments confirmed that CD-PEI-DOX has a stronger inhibitory effect on tumor growth, indicating that CD-PEI-DOX nanomedicine has inhibitory effects on tumors.

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19

BackgroundEffective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. MethodIn this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. ResultsA total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. ConclusionsAlthough randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating 102 the COVID-19 pandemic.

Targeted nano-vector for gene delivery into human bone marrow mesenchymal stem cells and cellular MR imaging in vitro / 中国医学影像技术

Objective To explore the feasibility and efficacy of an MRI-visible,targeted,nano-vector which is synthesized by attaching a targeting ligand,the GD2 single chain antibody (scAb GD2),to the distal ends of PEG-g-PEI-SPION as a carrier for gene delivery into human bone marrow mesenchymal stem cells (hBMSCs) and in vitro cellular MR imaging.Methods scAbGD2-PEG-g-PEI-SPION was synthesized as previously reported.Gel electrophoresis was performed to assess the pDNA condensation ability of scAbGD2-PEG-g-PEI-SPION.The particle size and Zeta potential of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes were observed by dynamic light scattering.Cytotoxicity of scAbGD2-PEG-g-PEI-SPI-ON was evaluated by CCK-8 assay using hBMSCs.Gene transfection efficiency of scAbGD2-PEG-g-PEI-SPION in hBMSCs was quantified by flow cytometry,PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION+ free AbGD2 and scAbIgG2a-PEG-g-PEI-SPION group was established.The cellular internalization of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes was observed by confocal laser scanning microscopy and Prussian blue staining.MRI of scAbGD2-PEG-g-PEI-SPION was performed by cellular MRI scanning in vitro.Results scAbGD2-PEG-g-PEI-SPION condensed pDNA to form stable nanocomplexes of 80-100 nm in diameter and showed low cytotoxicity to hBMSCs.At the same N/P ratio,the transfection efficiency of scAbGD2-PEG-g-PEI-SPION group was significantly higher than those of other groups (P＜0.001).At the optimal N/P ratio of 20,scAbGD2-PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of (59.60 ± 4.50) ％ in hBMSCs.Furthermore,hBMSCs labeled with scAbGD2-PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2/T2 *-weighted images in vitro.Conclusion scAbGD2-PEG-g-PEI-SPION is an efficient MRL visible targeted nano vector for gene delivery into hBMSCs.

Targeted nano-vector for gene delivery into human bone marrow mesenchymal stem cells and cellular MR imaging in vitro / 中国医学影像技术

Objective To explore the feasibility and efficacy of an MRI-visible,targeted,nano-vector which is synthesized by attaching a targeting ligand,the GD2 single chain antibody (scAb GD2),to the distal ends of PEG-g-PEI-SPION as a carrier for gene delivery into human bone marrow mesenchymal stem cells (hBMSCs) and in vitro cellular MR imaging.Methods scAbGD2-PEG-g-PEI-SPION was synthesized as previously reported.Gel electrophoresis was performed to assess the pDNA condensation ability of scAbGD2-PEG-g-PEI-SPION.The particle size and Zeta potential of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes were observed by dynamic light scattering.Cytotoxicity of scAbGD2-PEG-g-PEI-SPI-ON was evaluated by CCK-8 assay using hBMSCs.Gene transfection efficiency of scAbGD2-PEG-g-PEI-SPION in hBMSCs was quantified by flow cytometry,PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION+ free AbGD2 and scAbIgG2a-PEG-g-PEI-SPION group was established.The cellular internalization of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes was observed by confocal laser scanning microscopy and Prussian blue staining.MRI of scAbGD2-PEG-g-PEI-SPION was performed by cellular MRI scanning in vitro.Results scAbGD2-PEG-g-PEI-SPION condensed pDNA to form stable nanocomplexes of 80-100 nm in diameter and showed low cytotoxicity to hBMSCs.At the same N/P ratio,the transfection efficiency of scAbGD2-PEG-g-PEI-SPION group was significantly higher than those of other groups (P＜0.001).At the optimal N/P ratio of 20,scAbGD2-PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of (59.60 ± 4.50) ％ in hBMSCs.Furthermore,hBMSCs labeled with scAbGD2-PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2/T2 *-weighted images in vitro.Conclusion scAbGD2-PEG-g-PEI-SPION is an efficient MRL visible targeted nano vector for gene delivery into hBMSCs.

Interventional treatment for ischemic-type biliary lesion after liver transplantation / 器官移植

Objective To investigate the safety and efficacy of interventional treatment for ischemic-type biliary lesion (ITBL)after liver transplantation (LT). Methods The clinical and imaging data of 76 patients with ITBL after LT,who received interventional treatment in the Department of Interventional Vascular Radiology of the Third Affiliated Hospital of Sun Yat-sen University from January 2006 to February 2014,were retrospectively analyzed. On the basis of the cholangiographic appearance,patients were classified into 3 groups:hilar biliary stricture group (n=28),multifocal biliary stricture group (n=42),and biloma group (n=6). The modalities of interventional treatment were percutanous transhepatic biliary drainage (PTBD), PTBD combined with balloon dilation,PTBD combined with balloon dilation and plastic stent implantation. The methods of biliary drainage included external drainage and external-internal drainage. All the patients were followed up after treatment. The curative effect and biliary complication was observed. Results The first successful rate of PTBD was 97% (74/76). The total curative rate,improvement rate and ineffective rate of interventional treatment were 21% (16/76),51% (39/76)and 28% (21/76). In hilar biliary stricture group,the cure,improvement and inefficacy rates were 36% (10/28),57% (16/28)and 7% (2/28).The efficacy rate was 93% (22/28 ). In multifocal biliary stricture group,the cure,improvement and inefficacy rates were 14% (6/42),50% (21/42)and 36% (15/42). The efficacy rate was 64% (27/42). In biloma group,2 cases (2/6)were cured and treatment of4 cases was ineffective. The efficacy ofhilar biliary stricture group was better than that of multifocal biliary stricture group (P<0.05 ). The efficacy of multifocal biliary stricture group was better than that of biloma group (P <0.001 ). The main biliary complication was biliary tract infection during drainage. The rates of bile tract infections were 20% (13/64) and 67% (8/12)in patients with external drainage and external-internal drainage,respectively. There was significant difference between these two items (P <0.001 ). Conclusions PTBD is a safe and effective therapeutic modality for ITBL after LT,which combined with balloon dilation and biliary stent implantation can improve patients’clinical symptoms,elevate patients’quality of life. The biliary external drainage can decrease the rate of biliary tract infection significantly.

Percutaneous interventional therapy for anastomotic biliary strictures after orthotopic liver transplantation / 中华器官移植杂志

Objective To describe the technique, efficacy, and safety of percutaneous interventional therapy for anastomotic biliary strictures after orthotopic liver transplantation (OLT).Methods From May 2004 to December 2009, 25 patients with anastomotic biliary strictures afte OLT were enrolled in our study. The modalities of biliary drainage included external drainage in 22patients, and external-internal drainage in 3 patients who underwent re-transplantation. All patients accepted percutaneous interventional therapy in our hospital, including single PTBD in 4 patients,PTBD combined with balloon dilation in 14 patients, balloon dilation and plastic stent implantation in 5 patients, balloon dilation and metallic stent implantation in 2 patients. The drainage catheters were exchanged every 1 to 3 months. Results The success rate of PTBD was 100%. Of the all 25patients, 15 (60 %) patients were cured, and 10 (40 %) patients were improved. The effective rate was 100 %. The drainage catheters failed to pass through the narrow bile duct when initial PTBD in 7 patients, and success was achieved in 3 patients by operation again after biliary drainage for one week.In the other 4 patients, anastomotic bile ducts were occluded, which was confirmed by cholangiography after biliary drainage for 4 to 8 weeks. The rate of biliary tract infection was 24 % (6/25). No serious procedure-related complications occurred in the all 25 patients. Conclusion PTBD combined with balloon dilation and biliary stenting is a effective and safe therapeutic modality for anastomotic biliary strictures after OLT, which can improve the patients' clinical symptoms and elevate patients' quality of life. To avoid bile duct occlusion, the drainage catheters should be passed through the narrow segments of bile duct when initial PTBD.

Percutaneous transsplenic catheterization of portal vein: technique and clinical application / 中华放射学杂志

Objective To evaluate the feasibility of percutaneous transsplenic portal vein catheterization (PTSPC). Methods Thirty patients with portal hypertension underwent gastroesophageal variceal embolization via PTSPC route, 2 of which simultaneously underwent portal vein stenting. This study included the patients with portal venous obstruction ( tumor embolus or thrombus) or the patients with serious liver atrophy caused by liver cirrhosis. The patients who had severe coagulation insufficiency (with prothrombin time ＞ 20 s) were excluded. Of the 30 patients, 17 had primary hepatocellular carcinoma with main portal venous tumor embolus, 13 had cirrhosis with severe liver atrophy and(or) slight or moderate ascite. Before this study, all of 30 patients had a history of variceal bleeding, and 16 patients had a normal coagulation level, 10 patients had a mildly prolonged prothrombin time (14-17 s), 4 patients had a moderately prolonged prothrombin time (18-20 s). All of 30 patients underwent upper abdomen CT enhanced scanning before this procedure, and the site, direction, and depth of splenic vein branch puncture were decided by CT images. The technology of PTSPC, procedure-related complications, and its clinical application were retrospectively analyzed. Results PTSPC was performed successfully in 28 of 30 patients. Two cases failed because of a small intrasplenic vein. Procedure-related complications occurred in 6 patients (20. 0% ), which had decrease of hemoglobin concentration ( 15-50 g/L). Four of them needed blood transfusion. In the six patients, one patient (3.3%) with abdominal cavity hemorrhage had a serious drop of blood pressure 2 hours after procedure, whose clinical symptoms were relieved after four units of packed RBC and a great quantity of fluid were transfused. Twenty-eight patients whose PTSPC were successfullyperformed underwent variceal embolization, 2 of them were placed with portal vein covered stents. During a median follow-up period of 6 months (range: one to forty-two months), 14 patients died of hepatocellular carcinoma 1 to 12 months after procedure, and 2 patients died of hepatic failure caused by liver cirrhosis at fourteen months and twenty-three months after procedure, respectively. Variceal rebleeding was observed in 4 patients, the cumulative rebleeding rate at 1 year was 14.3%. Conclusion PTSPC is a feasible procedure, which provides a useful route for endovascular treatment of portal vein. However, hemorrhage at the puncture site after procedure should be noticed.

Role of multislice spiral CT in diagnosis of biliary complications after liver transplantation / 中华肝胆外科杂志

Objective To analyze the role of multislice spiral CT in the diagnosis of biliary com-plications following liver transplantation. Methods Forty-four patients with biliary complications re-ceived tri-phase contrast-enhancement CT examination and cholangiography (CP) within one week af-ter the CT scanning. Using the results of CP as the standard, we investigated the efficacy of multislice spiral CT for each kind of biliary complication. All the analyses for bile duct were based on the images on the late portal venous phase and the reconstruction of images performed with multiplan reformat,Results CP depicted biliary strictures involved in extrahepatic bile duct in 23 cases (including the common bile duct and common hepatic duct), left or right hepatic duct in 24 and intrahepatic bile duct in 27. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the CT examination were 91.3%, 83. 3% , 87. 8%, 87. 5% and 88. 2% for biliary stricture in extrahe-patic bile duct, 83. 3% , 88. 2%, 85. 4%, 90. 9% and 78. 9% for biliary stricture in left or right he-patic duct, 74.1%, 92.7%, 80.5%, 95.2% and 65.0%, for biliary stricture in intrahepatic bile duct, respectively. CT detected intrahepatic biloma in 4 cases and abscess in 2 but CP only detected biloma in 2 cases. The other 4 cases did not detected by CP because of severe biliary strictures which filled with biliary sludge. CP confirmed anastomotic bile leak in 3 cases. In these cases, CT only de-picted the fluid collection in hepatic hilum and abdominal cavity, none of the exact leak site could be detected. CP detected biliary sludge or stones in 33 cases. However, the sensitivity, specificity, accu-racy, positive predictive value and negative predictive value of the CT examination for biliary sludge or stones were 72.7%,100.0%,78.1%,100.0%and 47.6%,respectively.Meanwhile,in 1 patient with diffuse intrahepatic biliary strictures,active biliary bleeding was correctly detected by CT exami-nation and confirmed by hepatic arteriography.Conclusion Tri-phase contrast-enhancement CT exam-ination can be used as a general method for biliary complications after liver transplantation.Besides its benefits in biliary complications,it is of great value for depicting complications involved in hepatic pa-renchyma and acute biliary bleeding in the same examination.

Obstruction of hepatic vein or inferior vena cava after liver transplantation:the diagnosis and interventional treatment / 中华放射学杂志

Objective To investigate the diagnosis and interventional therapeutic technology for the obstruction of hepatic vein(HV)or inferior vena cava(IVC)after liver transplantation.Methods In the 831 patients who received orthotopic liver transplantation(OLT)and 26 patients who received living donor liver transplantation(LDLT),11 cases were confirmed with HV or IVC obstruction by venography and received interventional treatment from 2 to 111 days after liver transplantation.Of the 11 patients,five had the obstruction of HV anastomosis,five had the obstruction of IVC anastomosis,and one had the obstruction of HV and IVC anastomosis.In the eleven patients,five patients underwent OLT,four patients underwent LDLT,and two pediatric patients underwent reduced-size OLT.Before interventional treatment,9 patients received CT enhanced scans,2 received MR enhanced scans.Follow-up evaluations included liver or renal function tests,clinical symptom,and monitoring of HV or IVC flow.Pressure gradients before and after interventional treatment were compared by using a paired t test.The imaging data and interventional therapeutic technology of 11 cases were retrospectively analyzed.Results In all 11 patients,CT or MRI could clearly show congested areas of the liver,and the location and degree of HV or IVC obstruction.Of the 11 patients,four with HV obstruction and five with IVC obstruction were treated with stent placement,one with HV obstruction was treated with percutaneous transluminal angioplasty(PTA),one with HV and IVC obstruction was treated with HV PTA and IVC stent placement.Interventional technical success was achieved in all patients.The venous pressure gradient across obstruction was significantly reduced from(16.5±4.1)mm Hg(1 mm Hg=0.133 kPa)before the procedure to(2.9±1.7)mm Hg after the rocedure(t= 11.5,P＜0.01).Clinical improvement was noted in 10 patients except one pediatric patient who died of multiple-organs failure at the 9 th day after the treatment During the follow-up period of 9 to 672 days,two patients with PTA treatment had recurrent HV stenosis within one month after treatment,no patient with stent placement developed venous restenosis.No major complications occurred during the procedures.Conclusions Stent placement is safe and effective for HV or IVC obstruction after liver transplantation.CT or MRI before treatment is of important value for the diagnosis of congested areas of the liver,and the observation of HV or IVC obstruction.

Percutanous transhepatic biliary drainage for bile duct fistula after liver transplantation / 中华肝胆外科杂志

Objective To investigate the methods and efficacy of percutaneous transhepatic biliary drainage(PTBD)for the treatment of bile duct fistula related to orthotopic liver transplantation (OLT).Methods Seven patients(the median age was 40,from 25 to 56 years)with bile duct fistula related to OLT from January 2007 to May 2008 were analyzed retrospectively,including 6 receptors of OLT and 1 donor of living-donor liver tansplantation(LDLT),with anastomotic bile duct fistula and peripheral duct fistula of resection surface respectively.Of the 6 OLT receptors,hepatic artery stenosis occurred in 2 cases.All the patients underwent external biliary drainage(namely,with the drain tip in a pre-leak site).When the orificium fistulae was occluded and no bile drained from the drainage tube of abdominal cavity,the patients were diagnosed as cured.Results The mean output of the drainage tube was 350 ml/day(range 180-450 ml/day).After PTBD for 21 to 87 days(the median time was 62 days),the bile duct fistula was cured in all the 7 patients.During 93-675 days(the median time was 124 days)of follow-up,4 cases survived with normal level of health,2 cases gave up treatment for multiple-organ failure and 1 case died of hepatic function failure after hepatoma recurred.Biliary tract infection was occurred in 1 patient during PTBD.Conclusion PTBD could be proposed as a safe,effective and convenient method for treantment of bile duct fistula even in patients with poor general condition.

Diagnosis and percutaneous interventional management of hepatic venous outflow obstruction after adult-to-adult living donor liver transplantation: Two cases report and literatures review / 中国介入影像与治疗学

Hepatic venous outflow obstruction is a severe complication after liver transplantation, often occurs after living donor liver transplantation (LDLT). In this article, the clinical and imaging data of two patients with hepatic venous outflow obstruction after LDLT were analyzed retrospectively, and the related literatures were reviewed to explore the diagnosis and the interventional therapy of this complication. Hepatic venous outflow obstruction can be confirmed with percutaneous transhepatic venography. Percutaneous interventional managements, including balloon angioplasty and stent implantation are safe, easy and effective for the treatment of hepatic venous outflow obstruction after adult-to-adult living donor liver transplantation (A-A LDLT).

Biliary complications after liver transplantation: diagnosis with multi-Mice CT / 中华放射学杂志

Objective To evaluate multisliee CT in the diagnosis of biliary complications after liver transplantation. Methods Eighty-three consecutive patients who had undergone orthotopic liver transplantation (OLT) presented with clinical or biochemical signs of biliary complications and underwent contrast-enhancement CT examination. Three experienced radiologists, who were blinded to patient's clinical data, assessed CT images for the detection of biliary complications in consensus. Diagnostic confirmation of biliary complications was obtained with direct cholangiography in 69 patients, histologie study in 11 patients and hepatieojejunostomy in 3 patients. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT for the detection of biliary complications were calculated. In addition, CT features of anastomotie biliary stricture (ABS) were compared with those of non-anastomotie biliary stricture (NABS) using x2 test. Results A total of 62 biliary complications (74. 7% ) was eventually confirmed in the 83 patients, including ABS in 32 patients, NABS in 21 patients, biliary duct stones in 16 patients (of which 12 patients with biliary stricture), anastomotie bile leakage in 5 patients, biloma in 4 patients with biliary stricture, and biliogenic abscess in 2 patients with biliary stricture. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT for the detection of biliary stricture were 90. 6%、86. 7%、89. 2%、92. 3% and 83.9% , respectively. Other biliary complications, including biliary duct stones ( 16 cases) , anastomotic bile leak (5 cases) , biloma (4 cases), and biliogenic abscess (2 cases), were correctly diagnosed by CT; there was no false-positive or false-negative result. The incidence of irregular dilatation of bile duct was 71.4% ( 15/21 ), which was significantly higher in NABS cases than in ABS of 25.0% (8/32,P <0. 01 ) ; whereas the incidence of extrahepatie biliary dilatation was 33.3% (7/21) and regular dilatation was 14. 3% (3/21), which was significantly lower in NABS cases than in ABS of 84. 4% ( 27/32 ) and 68. 8% ( 22/32 ), respectively ( P < 0. 01 ). Of 21 patients with NABS, 66. 7% (14/21)complicated with hepatic artery stenosis or thrombosis, which was markedly more than that of NABS cases (15. 6%, 5/32,P <0. 01 ). Conclusions Multislice CT is a useful imaging procedure in the detection of biliary complications after liver transplantation, and biliary stricture can be primitively classified into ABS and NABS by CT. Hepatic artery ischemia is an important factor that causes NABS.