Research progress of exosome drug loading system / 中国药房

Exosome is a kind of vesicle secreted by a variety of cells with lipid bilayer membrane structure， which has good biocompatibility， high targeting and high stability， and is a natural nanoscale drug carrier with great development potential in drug delivery system. In this paper， exosomes and their properties， exosome drug delivery pathways and methods， the design strategy of engineered exosome drug delivery systems for targeted disease therapy， and the application of exosome drug delivery systems in the treatment of a variety of diseases were reviewed. Exosome drug delivery pathways could be divided into two categories： exogenous and endogenous. Common exosome drug delivery methods included electroporation， co-incubation， and ultrasound. Engineered exosome drug delivery system can further improve drug loading and enhance drug targeting. The main way of engineering is to modify exosome surface through genetic engineering technology， physical modification， chemical modification， etc. Exosome drug delivery system provides a new idea for targeted therapy of arthritis， tumor， brain and other diseases.

Effect of insulin-targeted glucose therapy on hemodynamics and cardiac function in organ donors / 中华器官移植杂志

Objective:To explore the effect of intensive insulin therapy on hemodynamics and cardiac function in organ donors.Methods:A total of 60 organ donors were randomly divided into two groups of intensive insulin therapy(IIT)and control(30cases each group). Blood glucose was adjusted at 6.2~10.0 mmol/L in control group and 4.4~6.1 mmol/L in IIT group.Blood glucose and insulin dosage during maintenance were recorded.Cardiac function values as well as serum inflammatory factor concentrations at admission and during donation were compared between two groups.Results:During maintenance, blood glucose was significantly lower in IIT group than that in control group [(5.1±0.6)vs(8.2±1.5)mmol/L, P<0.05] and insulin dosage was higher than that in control group [(9.5±3.2)vs(5.8±1.5)U/h, P<0.05]. As compared with control group, cardiac cycle efficiency(CCE), maximal rate of elevated pressure(DP/DT max)and left ventricular ejection fraction(LVEF)in were significantly higher in IIT group than those of control group.And serum cardiac troponin I(cTnI), N-terminal B-type natriuretic peptide(NT-Pro-BNP), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and high mobility group box-1 protein(HMGB1)as well as vasoactive-inotropic score(VIS)were significantly lower than those in control group( P<0.05). As compared with control group, cardiac donation rate of IIT group was significantly higher(30% vs 16.7%, P<0.05). Conclusions:Intensive insulin therapy and blood glucose control may blunt inflammatory response in organ donors, lessen myocardial injury and myocardial depression, stabilize hemodynamics and boost the rate of cardiac donation.

Epidemiological distribution of donor infection and drug resistance of main pathogens in organ donation after citizen's death / 器官移植

Objective To analyze the distribution characteristics and drug resistance of pathogens in infected donors from organ donation after citizen's death. Methods Clinical data of 465 potential donors from organ donation after citizen's death were retrospectively analyzed. The airway secretion, urine and blood samples of all donors were cultured. The infection rate of the donors, the source and composition ratio of pathogens were summarized. The drug resistance of main Gram-negative and Gram-positive pathogens was analyzed. Results Among 465 donors, 330 cases were infected and the infection rate was 71.0%. Among the positive culture samples of all donors, lower respiratory tract samples accounted for 63.8%(292/458), 18.6%(85/458) for blood samples and 17.7%(81/458) for urine samples. A total of 512 pathogens were isolated, including 75.0%(384/512) of Gram-negative pathogens, 18.2%(93/512) of Gram-positive pathogens followed by 6.8%(35/512) of fungi. Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were the most common Gram-negative pathogens. Klebsiella pneumoniae was sensitive to quinolones, compound preparations containing β-lactamase inhibitor (piperacillin-tazobactam, cefoperazone sodium-sulbactam sodium) and carbapenem antibiotics, whereas less sensitive to cephalosporins. Pseudomonas aeruginosa was sensitive to β-lactams, quinolones and aminoglycosides. Acinetobacter baumannii was sensitive to polymyxin, tigecycline and amikacin, whereas resistant to the other antibiotics. No Gram-positive pathogens was resistant to vancomycin, linezolid and teicoplanin. Staphylococcus aureus and coagulase-negative staphylococci were the most commonly isolated Gram-positive pathogens, which yielded resistance rates of 36% and 87% to oxacillin sodium, and were generally resistant to penicillin and erythromycin. The resistance rate of Enterococcus faecalis to quinolones and erythromycin exceeded 90%, and 55% for high-concentration gentamicin. Conclusions The infection rate of organ donors from organ donation after citizen's death is relatively high, and the main infection site is lung. Gram-negative pathogens are the most commonly isolated strains, and certain strains tend to exhibit multiple drug resistance.

Curcumin inhibits the proliferation and induces the apoptosis of nephroblastoma through activating miR-192-5p/PI3K/Akt signaling pathway / 中华微生物学和免疫学杂志

Objective:To study whether curcumin inhibits the proliferation and promotes the apoptosis of nephroblastoma through activating the miR-192-5p/PI3K/Akt signaling pathway.Methods:CCK-8 assay was used to investigate the effects of curcumin on the proliferation of nephroblastoma SK-NEP-1 cells and the appropriate concentration. The apoptosis rate of SK-NEP-1 cells was detected by V-FITC/PI. Luciferase reporter assay was used to verify the binding activity between miR-192-5p and PI3K. RT-PCR was performed to detect the expression of miR-192-5p at mRNA level. Western blot was used to detect the expression of PI3K and Akt at protein level.Results:Curcumin could significantly inhibit the proliferation of SK-NEP-1 cells and induce cell apoptosis in a dose-dependent manner. RT-PCR results showed that curcumin could significantly increase the expression of miR-192-5p. In addition, miR-192-5p significantly inhibited cell proliferation, induced cell apoptosis, and enhanced the effects of curcumin on the proliferation and apoptosis of SK-NEP-1 cells. Luciferase reporter assay suggested that miR-192-5p could bind to PI3K. Western blot results showed that curcumin down-regulated the expression of PI3K and Akt at protein level by mediating the expression of miR-192-5p.Conclusions:Curcumin could inhibit the proliferation and induce the apoptosis of nephroblastoma cells through mediating the expression of miR-192-5p and further inhibiting the downstream PI3K/Akt signaling pathway.

Clinical application of Taylor spatial frame in adjustment of lower extremity force line of knee medial compartmental osteoarthritis / 中国修复重建外科杂志

Objective: To explore the safety and effectiveness of Taylor spatial frame (TSF) in the treatment of medial compartmental osteoarthritis (MCOA) of the knee and the adjustment of the lower extremity force line at the same time. Methods: The clinical data of 30 patients with MCOA who underwent high tibial osteotomy (HTO) between October 2016 and April 2017 were retrospectively analyzed. According to the different fixation methods, they were divided into external fixation group (TSF external fixation, 16 cases) and internal fixation group (locking steel plate internal fixation, 14 cases). There was no significant difference between the two groups in gender, age, side, disease duration, mechanical femur tibia angle (MFTA), and other general data ( P>0.05). The operation time and intraoperative blood loss of the two groups were recorded and compared; MFTA was used to evaluate the recovery of the lower extremity force line at last follow-up; Hospital for Special Surgery (HSS) score was used to evaluate the clinical effecacy before operation and at 2 weeks, 1 month, and 3 months after operation. Results: The operation time and intraoperative blood loss of external fixation group were significantly less than those of internal fixation group ( P0.05). Conclusion: TSF has unique advantages in HTO treatment of MCOA patients and correction of lower extremity force line, such as shorter operation time, less bleeding, firm fixation, and less complications. It can accurately adjust the lower extremity force line after operation and has good effectiveness. It is an effective and safe fixation method.

Effect of axial load test in assisting Taylor spatial frame for tibia and fibula fractures / 中华创伤杂志

Objective To investigate the effect of axial load test in Taylor spatial frame treatment of external fixation for tibia and fibula fractures.Methods A retrospective case-control study was conducted to analyze the clinical data of 36 patients with open fracture of tibia and fibula admitted to Tianjin Hospital from March 2015 to June 2017.There were 22 males and 14 females,aged 21-71 years[(46.1±14.2)years].All patients received Taylor spatial frame external fixation for tibia and fibula fracture within 1 week after injury.After operation,18 patients received axial load test(experiment group),and the other 18 did not(control group).When the value of axial load test was less than 5% in experiment group,the Taylor spatial frame was removed.The control group used traditional method to remove the Taylor spatial frame.Comparisons were made between the two groups in terms of treatment duration,total cost,re-fracture after Taylor spatial frame removal and incidence of stent-tract infection.Results All patients were followed up for 3-14 months with an average of 8.6 months.Compared with control group,the treatment duration[(36.17±11 .44)weeks vs.(44.50±9.16)weeks]and total cost[(93.7±7.9)thousand yuan vs.(120.1±10.6)thousand yuan]of experiment group were significantly lower(P＜0.05).In the experiment group,there was 0 patient with re-fracture and two patients with stent-tract infection,with the complication incidence of 11%,while there were two patients with re-fracture and three patients with stent-tract infection,with the complication incidence of 28% in the control group(P＞0.05).Conclusions After Taylor spatial frame external fixation for tibia and fibula fractures,regular axial load test can safely and timely guide the removal of Taylor spatial frame.It can reduce the treatment duration and cost compared with the traditional removal method,being safe and reliable.

A twenty-year review of clinical liver transplantation / 中华危重病急救医学

Objective To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. Methods The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. Results The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. Conclusions The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.

A clinical report of split liver transplantation in pediatric recipients / 中华器官移植杂志

Objective To summarize the clinical experience in pediatric split liver transplantation (SLT) recipients.Methods A retrospective analysis was conducted on 38 cases of pediatric recipients using split donors during February 2007 to December 2015.The ex situ splitting technique was used for 22 grafts and in situ splitting technique was used for the rest 16 grafts.The survival rate of patients,recovery of liver function,re-transplantation rate,incidence of vascular complications and biliary complications were Observed,and the causes of death were analyzed.Results The median follow-up time of all the patients was 30.65 months (0.1-96.6 months).The 1-and 3-year cumulative survival rate was 81.6％ and 76.3％ respectively.The re-transplantation rate was 13.16％,the incidence of vessel complications was 31.58％,and biliary complication rate was 31.58％.There were 9 deaths,including 5 deaths which were related to surgical complications.Conclusion SLT can expand the resource of 1iver donors for pediatric recipients.Comparing to ex situ split liver grafts,in situ split liver grafts can reduce morbidity and mortality of children after liver transplantation.

A clinical report of split liver transplantation in pediatric recipients / 中华器官移植杂志

Objective To summarize the clinical experience in pediatric split liver transplantation (SLT) recipients.Methods A retrospective analysis was conducted on 38 cases of pediatric recipients using split donors during February 2007 to December 2015.The ex situ splitting technique was used for 22 grafts and in situ splitting technique was used for the rest 16 grafts.The survival rate of patients,recovery of liver function,re-transplantation rate,incidence of vascular complications and biliary complications were Observed,and the causes of death were analyzed.Results The median follow-up time of all the patients was 30.65 months (0.1-96.6 months).The 1-and 3-year cumulative survival rate was 81.6％ and 76.3％ respectively.The re-transplantation rate was 13.16％,the incidence of vessel complications was 31.58％,and biliary complication rate was 31.58％.There were 9 deaths,including 5 deaths which were related to surgical complications.Conclusion SLT can expand the resource of 1iver donors for pediatric recipients.Comparing to ex situ split liver grafts,in situ split liver grafts can reduce morbidity and mortality of children after liver transplantation.

Analysis of long term biliary complications and survival of liver transplantation from organ donation after citizen's death / 中华器官移植杂志

Objective To evaluate the clinical effect,the incidence of postoperative biliary complications and the survival of liver transplantation from Chinese donation after citizen's death (DCD).Methods The clinical characteristics of donors and recipients,survival of allografts and recipients,and postoperative biliary complications of 169 cases of DCD liver transplantation from October 2013 to June 2015 were analyzed retrospectively.Results The overall biliary complication rate was 8.28％ (14/169).There were 6 cases of ischemic cholangiopathy [3.55％ (6/169)].In 37 cases receiving donation after brain death liver transplantation,the incidence of biliary complications was 8.11％ (3/37),and ischemic biliary disease occurred in 1 case with the incidence being was 2.70％.In 132 cases of donation after cardiac death liver transplantation,biliary complication rate was 8.33 ％ (11/132),and there were 5 cases of ischemic biliary disease with the incidence being 3.79 ％.There was no significant difference in the incidence of bile duct complications of the recipients between brain death and cardiac death organ donation (P＞ 0.05).The 1-,2-,and 3-year survival rate of patients and grafts of donation after brain death was 94.5％,89.2％ and 83.7％,and 94.5％,86.5％ and 81.1％,respectively.The 1-,2-,and 3-year survival rate of patients and grafts of donation after cardiac death was 93.9％,88.6％ and 83.3％,and 91.7％,86.4％ and 80.3％,respectively.There was no significant difference in survival of recipients and grafts between brain death and cardiac death organ donation (P＞0.05).The mean warm and cold ischemia time of donation after cardiac death was 13.59 min and 3.32 h respectively.Conclusion The outcome of DCD liver transplantation is satisfactory.The incidence of overall biliary complications and ischemic biliary disease of cardiac death donor liver transplantation was close to that of brain death donor liver transplantation.

Establishment of Modified Brain Death Model in Pig / 天津医药

Objective To establish a stable and reliable model of brain death in swine, and to provide a more stable model for investigating pathomorphology in brain tissue and for studying transplantation immunology during brain death. Methods Base on the classic methodology of increasing epidural intracranial pressure, Codman intracranial pressure moni-toring probes were implanted in landrace pigs invasively. According to the relationship between ICP and MAP, brain death models were established by increasing intracranial pressure slowly and intermittently, with real-time monitoring of the intra-cranial pressure. Results Among twelve experimental landrace pigs, one died from anesthetic accident, while the rest elev-en were successfully established as brain death models. With effective respiratory and circulatory support, those brain death models can be maintained for (31.3 ± 4.7) h. Brain death model establishement is a stable and reliable process demonstrated by transcranial Doppler, EEG, ECG, mean arterial blood pressure and other monitoring methods. After brain death is con-firmed, animal models can be maintained for a long time. Conclusion Our methodology of inducing brain death model un-der ICP monitoring is stable and easy to be standardized. It can also provide a more stable model for studying brain tissue pathomorphology and transplantation immunology.

Single center's experience of ABO-incompatible liver transplantation in 20 cases / 中华普通外科杂志

ObjectiveTo summarize 20 ABO-incompatible liver transplantation cases in our hospital and explore the treatment strategy. MethodsFrom January 2009 to July 2011,20 cases donorrecipient ABO blood type not-identical liver transplantation was performed at our hospital. 16 cases were ABO-incompatible(ABO-Ⅰ) and 4 were ABO-compatible(ABO-C ).The median follow-up was (13.3 ± 9.2) months.ResultsExcept preoperative MELD score,there were no significant difference in other perioperative data,the incidence of postoperative complications and the cumulative survival rate between ABO-C and ABO-Ⅰ group.There were 5 deaths in 20 cases,2 cases in ABO-C group and 3 cases in ABO-Ⅰ group,survival rate was 75％.The cause of death was perioperative multiple organ failure in 2 cases,liver cancer recurrence in 2 cases and cerebral hemorrhage in 1 case.There were 2 cases of acute rejection,3 cases of biliary complications and 3 cases of portal vein thrombosis developing postoperatively. Eleven patients had increased serum creatinine after operation,preoperative high creatinine existed in 6 cases and it maintained posttransplant high level for more than 7 days,the serum creatinine level in other 7 patients was back to normal level in 7 days.ConclusionsA combination splenectomy before the portal vein reperfusion,the protocol of basiliximab,tacrolimus (TAC)/mycophenolate mofetil (MMF)/steroids immunosuppression treatment,postoperative peripheral vascular dilatation treatment by Alprostadil,help achieve favorable outcome in selected patients who underwent ABO-incompatible liver transplant.

Single-center experience of organ donation after cardiac death / 中华器官移植杂志

Objective To summarize our experience of harvesting and using the organs of donors after cardiac death.MethodsForm March 2010 to October 2011,56 potential donors were diagnosed with cardiac death,who conformed to the classification of Maastricht Ⅲ criteria.There were 40 failure cases whose family refused to donate,and one failure case who suffered from serious infection.Finally,the success ratio of donation after cardiac death was 26.8％ (15/56).Twelve livers and 22 kidneys were transplanted into 12 and 20 recipients respectively.ResultsTwelve cases of liver transplantations had acceptable outcomes. The grafts of 4 cases out of 20 cases of kidney transplantations were removed after transplantation,and other recipients had acceptable outcomes.ConclusionCitizens organ donation after cardiac death can expand the number of suitable organs,but we need to strictly control the criteria for potential donors.

Diagnosis and treatment of hepatic venous outflow obstruction after pediatric liver transplantation / 中华肝胆外科杂志

ObjectiveTo investigate the diagnosis and treatment of hepatic venous outflow obstruction(HVOO) after pediatric liver transplantation.MethodsFrom Jan.2000 to Dec.2009,48 children received liver transplantation in the Department of Liver Transplantation,First Central Hospital,Tianjin.There were 3 patients who developed HVOO (2 received liver transplantation in our center,while the third from another centre).The HVOO was diagnosed by color Doppler ultrasound (CDUS),computed tomography (CT),and angiography of inferior vena cava (IVC).The patients received balloon dilation and/or stent placement and followed-up with regular monitoring.ResultsIn our center,the incidence rate of HVOO was 4.17％ (2/48).The time of onset was 2 months to 1 year postoperatively.The pressure gradient between the hepatic vein and the right atrium was from 6 to 30mmHg.After treatment,the venous pressure gradient decreased from 4 to 10mmHg.Resolution of clinical symptoms was achieved in these patients.HVOO relapsed in two patients who received balloon angioplasty only.The clinical symptoms were relieved after repeated balloon dilation in one and stent placement in the other.There were no further complications after these procedures.All patients were alive at a follow-up from 2 months to 9 years.ConclusionThe incidence of HVOO after pediatric liver transplantation was not high,but HVOO led to serious consequences.Balloon dilation and/or stent implantation were safe and efficacious treatments for HVOO after pediatric liver transplantation.

Orthotopic liver transplantation in donation after cardiac death: a report of 7 cases / 中华器官移植杂志

Objective To study the prognosis of patients with end-stage liver cirrhosis who using controlled cardiac death liver donor in situ liver transplantation. Methods Seven cases of transplants which used liver donated after cardiac death were done in our center. The preoperative and postoperative data were analyzed. The prognosis of these patients was observed. Results Except one recipient died of upper gastrointestinal bleeding at the 9th day after surgery, the remaining 6 patients were followed up for more than 12 months (mean 15.7 months) and the prognosis was satisfactory.Conclusion Patients can get good prognosis after the liver transplants with donated liver after cardiac death which meets the Maastricht Classification type Ⅲ.