BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cellbased administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intraarticular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

The pathology of liver allograft biopsy is not only essential for the evaluation of liver donor, but also for the diagnosis and differential diagnosis of posttransplantation complications. With the development of liver transplantation in clinical practice, relevant studies of the pathological diagnosis of liver allograft complications have been deepened. Banff classification on liver allograft pathology have been gradually established within the international community. In China, pathological studies related to liver allograft pathology have been steadily carried out, and the pathological diagnostic basis of liver allograft pathology suitable for the clinical practice of liver transplantation in China has been gradually formed. This article reviews the history of Banff liver allograft pathology and major pathological lesions of liver allograft complications, aiming to provide reference for implementing pathological diagnosis of liver allograft pathology in China, assisting clinical diagnosis and targeted treatment of complications after liver transplantation, and further improving the survival of liver allograft and recipients.

Alcoholic hepatitis (AH) is an acute severe decompensated alcoholic liver disease (ALD), commonly occurring in heavy drinkers. The pathogenesis of AH is still not fully understood, which may be related to the interactions of multiple complex factors such as alcohol metabolism, inflammation and heredity, etc. Under the background of continuous alcoholic exposure, the pathological changes include hepatocyte steatosis, liver inflammation and fibrosis occurring in the body. This paper summarizes the recent research literatures related to the clinicopathological features, pathogenesis and prognosis evaluation of ALD to comprehensively understand the pathogenesis and pathophysiological characteristics of AH in order to provide theoretical basis for clinical diagnosis and treatment of this disease.

Objective: To compare the efficacy of intra-articular injection of autologous platelet-rich plasma (PRP) with that of sodium hyaluronate for patients with knee osteoarthritis (KOA). Methods: Fifty KOA patients were randomly divided into a PRP group (n=25) and a sodium hyaluronate group (n=25). Those in the PRP group were injected intra-articularly with 5 ml of autologous PRP every 2 weeks for 6 consecutive weeks, while the sodium hyaluronate group was given intra-articular injections of 2 ml of sodium hyaluronate once a week for 6 weeks. Both groups performed isokinetic strength training three times a week for 6 weeks. Before as well as 6 weeks, 3 months, 6 months and 12 months after the treatment, both groups were followed and evaluated using the Western Ontario and McMaster University osteoarthritis index (WOMAC). A Biodex System 4 isometric muscle strength testing system was used to evaluate the knees′ peak torque (PT) in flexion and extension, total power (TW), and average power (AP). Results: Before the treatment there were no significant differences in pain, stiffness or average WOMAC score between the two groups. Afterward significant improvement was observed in the pain, stiffness and WOMAC scores of both groups. Compared with the sodium hyaluronate group, significantly greater decreases in the average WOMAC pain score were observed in the PRP group after the different intervals. That was also true of the average stiffness scores and the overall average WOMAC scores after 6 and 12 months. The flexor and extensor PT, TW and AP at the angular velocities of 60°/s and 90°/s also improved significantly in both groups after 6 weeks and 12 months, with the improvement of the PRP group significantly greater than that in the control group at the same time points. Conclusion Intra-articular injection of either autologous PRP or sodium hyaluronate can effectively alleviate the clinical symptoms of KOA when combined with isokinetic strength training. However, PRP is the more effective. Its use is worthy of clinical application and promotion.

Objective To explore the changes and significance of hepatic cytokines during ischemia and reperfusion in rats undergoing donation after circulatory death (DCD) liver transplantation in different functional warm ischemic durations.Methods Maastricht Ⅲ DCD liver transplantation was simulated and a rat model of functional warm ischemia established.DCD liver transplantation was established by cutting diaphragm.There were four groups of functional warm ischemia 0/15/30 min and living donor liver transplantation control.Liver tissues and serum samples were obtained after donor liver acquisition and 6-hour reperfusion respectively.Luminex liquid chip was employed for detecting the concentrations of 23 cytokines in liver tissue,superoxide dismutase or malondialdehyde (SOD/MDA) expression in liver tissue and alanine transaminase or aspartate aminotransferase (ALT/AST) expression in sera.And hematoxylin-eosin (HE) staining was utilized for detecting liver tissue damage.Results The levels of cytokines in liver tissues during ischemia and reperfusion were significantly different in different functional warm ischemic durations.SOD/MDA in liver tissue,AST/ALT in sera and pathological examinations also showed that,with the prolongation of functional warm ischemic duration,the degree of liver tissue injury gradually aggravated.Conclusions Functional warm ischemic duration has a significant effect on cytokines during ischemia and reperfusion in rat DCD liver transplantation.This phenomenon can help us further elucidate the mechanism of ischemia-reperfusion injury and provide new ideas for preventing ischemia-reperfusion injury during DCD liver transplantation.

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.
China ; Humans ; Liver Transplantation

Objective The purpose of this study was to explore common complications and their clinicopathological features in pediatric liver transplantation.Methods Clinical and pathological data of 240 liver biopsies from 168 children that conducted liver puncture from January 2015 to May 2018 in Tianjin First Central Hospital was retrospectively analyzed.We comprehensively analyzed incidence rate and pathological features of various complications,and correlations between acute rejection and C4d staining result or Banff score.Results A total of 86.67％ (208/240) liver biopsies could be definitely diagnosed with incidence rate of main complications in descending order as follows:T cell mediated rejection (TCMR) 60.57％ (126/208),drug-induced liver injury (DILI) 17.31％ (36/208),biliary complication 8.17％ (17/208),vascular complication 3.37％ (7/208),ischemia/reperfusion injury (IRI) 2.88％ (6/208),antibody mediated acute rejection (AMR) 1.92％ (4/208),HBV infection 1.92％ (4/208),non-alcoholic fatty liver disease (NAFLD) 1.44％ (3/208),chronic rejection (CR) 0.96 ％ (2/208) and HCV infection 0.48 ％ (1/208).TCMR and AMR in acute rejection (AR) accounted for 96.92％ (126/130) and 3.08％ (4/160),and into(portal-based,PB)type TCMR accounted for 96.03％(121/126) with the detectable rate of BP type subtype TCMR of 26.45％(32/121)within 30 d.There were 65.87％ (83/126)、25.40％ (32/126) 和4.76％ (6/126) of BP TCMR samples with "Banff ACR RAI" score within 3-5,6-7 and 8-9,and RAI score was negatively correlated with postoperative time (r =0.127,P =0.084).The incidence rate of central perivenulitis (CP) and portal eosinophils infiltration (PEI) in BP TCMR was 63.63％ (77/121) 和43.80％ (53/ 121),respectively,additionally,the PEI level was positively correlate with RAI score (P＜0.05).CP TCMR and AMR occurred within 30d-365 d and 8 d-180 d,respectively postoperative,while,the two CR occurred at 1095 d and 1335 d postoperative,and significant correlation was strikingly observed between rejection subtype and postoperative time (Z =9.231,P =0.026).C4d positive rate was 10％ (24/240),which was associated with Banff score and postoperative time,besides,C4d score was also correlated with rejection subtype and RAI score.The occurrence of DILI was mainly at time of ＜90 d or ＞180 d postoperative,and the detectable rate of biliary complication within 180 d postoperative was 82.35％ (14/17),IRI Appear in ＜30d.Hepatic artery complication account for nearly 57.14％ (4/7),occurrence time is ≤90 d.Occurrence of HBV infection,CMV infection and NAFLD were mainly at ＞365 d,＜90 d and ＜365 d,respectively.Conclusion There were lots of differences in clinical and pathological features among multi pediatric liver transplantation complications.Liver puncture plays an important role in rejection subtype classification and grading,as well as in non-rejection complications identification.

Objective To explore the effect of sling exercise therapy (SET) for improving the balance and walking ability of patients with incomplete paraplegia.Methods The 37 patients were randomly divided into two groups:19 patients in the observation group and 18 cases in the control group.Both groups were given conventional rehabilitation training,including bridge training on the mat,kneeling position training,sit-stand training and orthosis walking training.The observation group was additionally provided with sling exercise therapy with multi-point,muhi axis sling suspension supine,prone with a neutral lumbar spine,supine with pelvic elevation and in a lateral position like an arch.Before the treatment and 6 weeks after the treatment,trunk control tests (TCTs) were administered.The Berg balance scale (BBS) and Holden's walking function classification were used to assess the subjects' balance and walking ability.Results There were no significant differences in the two groups' average TCT and BBS scores before the treatment.After 6 weeks of treatment the average scores of both groups had increased significantly,with a significantly bigger increase observed in the observation group.After the treatment,the average Holden classification of the observation group was significantly superior to that of the control group.Conclusion SET in addition to conventional rehabilitation training can significantly improve the balance and walking ability of patients with incomplete paraplegia.It is worthy of application in clinical practice.

Objective To study the effect of isokinetic strength training on upper limb motor function and activities of daily living (ADL) in stroke patients with hemiplegia. Methods From January to December, 2016, 56 stroke patients with hemiplegia were randomly di-vided into control group and observation group equally. Both groups received routine rehabilitation training, and the observation group ac-cepted hemiplegic limb flexor and extensor muscle isokinetic strength training in addition, for four weeks. They were assessed with Fugl-Meyer Assessment-upper limb (FMA-UL), modified Ashworth Scale (MAS), modified Barthel Index (MBI) and biomechanical index-es of elbow flexion and extension with Biodex System-4 before and after treatment. Results The scores of FMA and MBI improved after treatment (t>7.083, P<0.001) in both groups, and improved more in the observation group than in the control group (t>2.369, P<0.05). The peak torque, total work and average power at 60°/s and 120°/s angular velocity of both flexor and extensor improved in both groups (t>2.149, P<0.05), and those of the extensor improved more in the observation group than in the control group (t>2.027, P<0.05), except the peak torque at 60°/s angular velocity. Conclusion Isokinetic strength training can improve the motor function of upper limbs and activities of daily living in stroke patients with hemiplegia.

Objective To investigate the effect of portal vein ligation combined with in situ splitting on liver regeneration in rats .Methods Seventy-five healthy male Sprague-Dawley rats were selected and randomly assigned into sham operation group ( S) , portal vein ligation group ( PVL) and portal vein ligation combined with in situ splitting group ( ALPPS) .On 1 d, 3 d, 7 d, 10 d, 14 d after operation , the hepatic regeneration rate ( HRR) of right median lobe was calculated , the serum alanine aminotransferase ( ALT) , aspartate aminotransferase (AST), IL-6, HGF, VEGF were detected.mRNA of IL-6, HGF, TNF-α, TGF-βwas assayed by real-time PCR, and the hepatic proliferating cell nuclear antigen ( PCNA) labeling index was evaluated by immunohistochemistry .Results Comparing with PVL group , the HRR of the right median lobe obviously increased on day 3, 7, 10 and 14 in ALPPS group (P<0.05), and ALT and AST level were increased on 1 d (P<0.05).On day 1 and 3, the content of serum IL-6, HGF and VEGF were all in-creased in ALPPS group [(70.7 ±14.6) pg/ml vs.(134.2 ±31.4) pg/ml; (0.70 ±0.04) ng/ml vs. (0.74 ±0.02) ng/ml;(82.1 ±12.6) pg/ml vs.(103.5 ±14.7) pg/ml], respectively (P<0.05).The mRNA expression of IL-6, HGF, TNF-α, TGF-βand the PCNA labeling index were also increased in ALPPS group in comparison with those in PVL group on day 1 and 3 (P<0.05).All the indexes in the two groups were all higher than those in the group S ( P<0 .05 ) .Conclusions Portal vein ligation combined with in situ splitting could significantly enhance liver regeneration .The possible mechanisms were related to the inflammation reaction and stress response caused by in situ splitting and up-regulation of cytokines in the regenerating lobe after portal vein ligation combined with in situ splitting , especially IL-6, HGF and TNF-α.