Objective To explore the value of the Accordion severity grading system (ASGS) in predicting short-term outcomes after orthotopic liver transplantation for severe hepatitis by classifying post-surgery complications.Methods The clinical documents of 159 patients were retrospectively analyzed who underwent orthotopic liver transplantation for severe hepatitis between Aug.1,2004 to Sept.1,2014 at our center.Complications were categorized according to the ASGS:grade 1 (mild),grade 2 (moderate),grade 3-5 (severe),and grade 6 (death).Outcome measures included ventilator support time,the length of ICU stay,postoperative recovery time.Spearman rank correlation analysis was used to test the correlation between the different grades with these outcome measures.1-year survival trends of different grade complication groups were demonstrated by Kaplan-Meier method and compared by Log-rank test.Results In total,43 (27.0％) patients had a grade 2 complication;41 (25.8％) grade 3;31 (19.5％) grade 4;9 (5.7％) grade 5;and 35 (22.0％) grade 6.There was no grade 1 patient.There was a significant correlation between the complication grades and the ventilator support time,the length of ICU stay and postoperative inpatient time (P＜0.01).With the increase of the complication grades,the outcome measures were even worse.Severe grade complication group had a longer ventilator support time,the length of ICU stay and postoperative inpatient time than the moderate grade complication group (P＜0.01).There was a significant downward trend in 1-year survival with the increase of the complication grade (P＜0.01).Conclusion The ASGS is helpful to assess risks and predict short-term outcomes after liver transplantation for severe hepatitis.Higher Accordion grades are correlated with even worse short-term outcomes.

Objective To study the therapeutic effect of EUS-guided rendezvous (EUS-RV) when ERCP failed in patients with malignant obstructive jaundice. Methods 12 cases of malignant obstructive jaundice patients were underwent EUS-RV after unsuccessful ERCP. The operation success rate, liver function recovery 1 week and 1 month after operation, complication rates, hospital stay and patient survival were observed. Results All 12 patients were successfully operated and placed stents by endoscopic ultrasound puncture following by ERCP: 8 patients by the stomach, 4 patients by duodenum, the operation success rate was 100.00%; There were significant difference between the liver function recovery of preoperative and postoperative one week or postoperative one week and postoperative one month (P < 0.05). 1 bleeding occurred and were improved after conservative treatment, the complications rate was 8.33%; the hospital stay was (20.68 ± 5.76) d; the average survival time of patients was 224 d. Conclusion EUS-guided rendezvous may be the alternative treatment due to the diminutive trauma and good effect when ERCP failed in patients with malignant obstructive jaundice.

Objective The treatment of anti-neutrophil cytoplasmic antibodies ( ANCA) associated vasculitis ( AVV) such as mycophenolate mofetil ( MMF ) can improve the remission rate, however, it also results in high recurrence rate and high incidence of adverse reaction related to the treatment.The article was to observe the clinical efficacy and safety of multi-target therapy ( MT ) in the treatment of AAV with renal involvement. Methods Retrospective observation was made on 7 AVV patients treated with multi-target therapy in our department from June 2009 to October 2013.The pa-tients (1 male, 6 females) aged from 21 to 54 years were accompa-nied with renal damage and serum creatinine (SCr≤3 mg/dL).All patients had positive myelopeeroxidase-ANCA (MPO-ANCA), high-grade proteinuria and hematuria.4 patients had elevated SCr (1.47-2.94 mg/dL) with EGFR<60 mL/min, 3 patients had normal SCr ( EGFR>90 mL/min in 2 patients and EGFR<90mL/min in 1 patient) .The renal histological classification included focal type (n=5) and crescentic type (n=2).All patients received MT therapy which was composed with the steroids, MMF (0.5-0.75g/d) and FK506 (1.5-3 mg/d).The remission rate, the change of renal function, proteinuria and ANCA, adverse reaction and relapse were investigated. Results The patients had received MT for 6 to 24 months ( median 12 m) and had been followed up for 9 to 53 months ( median 46 m).All patients achieved remission during MT induction treatment.The Birmingham vasculitis activity score (BVAS) decreased from 14 (6~16) to 0, without urinary sediment, and complete remission of proteinuria was found in 6 patients. Before the therapy the EGFR expression was normal in 1 patient and 64.8-87.4 mL/min in 3 patients among 4 patients (EGFR<60 mL/min) , and the EGFR expression became normal in 3 patients ( EGFR>60 mL/min) .At the end of follow-up, the EGFR expres-sion was normal in 4 patients, 60-90 mL/min in 1 patient and less than 60 mL/min in 2 patients, without end stage renal disease. ANCA level turned to normal in 3 patients and significantly decreased in 4 patients.No patients had adverse reaction, died, or re-lapsed during the follow-up. Conclusion MT is effective in the control of renal activities of AVV patients with mild or moderate re-nal function damage.It attributes to great improvement of renal function and urine protein, as well as good tolerance.However, pro-spective study is required to confirm the efficacy of this new therapy.

BACKGROUND:At present, there are few reports about the non-human primate models of type 2 diabetes mel itus in domestic and abroad, so it lacks of standardized production methods and evaluation criteria.
OBJECTIVE:To establish a safe and effective type 2 diabetes mel itus model of rhesus monkey and evaluation method.
METHODS:Twelve rhesus monkeys were randomly assigned to experimental group (n=9) and control group (n=3). Rhesus monkeys in the experimental group were fed with high-glucose and high-fat diet for 4 weeks, and intraperitoneal y injected with 30 mg/kg streptozotocin to establish models of type 2 diabetes mel itus. Rhesus monkeys in the control group were fed with an equal volume of physiological saline. At 12 weeks after injection, peripheral blood serum was col ected to measure fasting blood glucose, lipids, insulin, and C-peptide levels. Intravenous glucose tolerance test and C-peptide release test were used to detect pancreatic gland and pancreatic islet function. Histopathological examination was performed in pancreas, kidney and liver.
RESULTS AND CONCLUSION:(1) 12 weeks after injection, fasting blood glucose, triglycerides, and total cholesterol levels were significantly higher in the experimental group than in the control group (P<0.05). Insulin and C-peptide levels were significantly lower in the experimental group than in the control group (P<0.05). (2) The area under the curve for intravenous glucose tolerance test was increased in the experimental group than in the control group (P<0.05). The area under the curve for C-peptide response test was significantly reduced in the experimental group than in the control group (P<0.05). (3) The pathological sections of pancreas, kidney and liver showed typical pathological changes of diabetes in the experimental group. (4) It is confirmed that we got high achievement about rhesus monkey models of type 2 diabetes mel itus made by high-glucose and high-fat diet combined with low-dose streptozotocin. It is a feasible, safe and effective method.

Objective To study the effects of adjuvant Huaier on long-term survivals after curative partial hepatectomy for primary liver cancer.Methods 175 patients with primary liver cancer who received curative partial hepatectomy from January 2002 to January 2006 were divided into two groups:the treatment group (group A,n =87) and the control group (group B,n=88).Group A was treated with Huaier (60 g per day for 6 months) after the operation while group B received no Huaier treatment.Results The overall 1-,3- and 5 year survival rates and disease-free survival rates were 91.90％,73.90％,and 56.0％ and 68.1％,48.4％ and 40.2％,respectively.The overall 1-,3-and 5-year survival rates in group A were significantly higher than group B (91.80％,79.30％,65.2％ vs 92.0％,68.3％,46.6％,P 0.038).In addition,the 1-,3-and 5-year survival rates after tumor recurrence in group A was also significantly higher than group B (78.6％,46.9％,38.2％ vs 69.0％,16.8％,12.6％,P=0.040).Multivariate analysis showed that the use of Huaier,hepatitis infection,severity of cirrhosis,vascular cancer thrombus were the most important prognostic factors for overall long-term survival (P＜0.05).Blood transfusion and histological grade were independent risk factors for disease free survival.The use of Huaier and the clinicopathological type were significantly co-related to the survival from recurrence/metastasis to death.Conclusion The use of Huaier improved disease free survival and the survival from recurrence or metastasis for patients with primary liver cancer following curative hepatectomy.

BACKGROUNDHigh-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma. The plasma concentration of MTX is closely related to efficacy and toxicity. There are large individual differences. Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances. However, no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported. The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients, and to explore the influence of patient covariates and between-occasion variability on drug disposition.

METHODSAn intravenous HD-MTX solution (10 g/m 2 ) was given 274 times to 148 osteosarcoma patients. MTX plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after commencement of the infusion, and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations. The PPK model and parameters were estimated using NONMEM software. The effects of fixed-effect factors were evaluated, and the final regression model was obtained.

RESULTSThe following population parameters were obtained using a two-compartment model: CL1 (clearance of central compartment): (CL1 ) = CL1TV × [1 - θ CL1- MTXNUM × MTXNUM] × [1 - θ CL1- CrCl1 × (CrCl1 - 1.89)] × e ηCL1i (L/h). V1 (central volume): (V1)i = V1TV × e ηV1i (L). CL2 (clearance of peripheral compartment): (CL2)i = CL2TV × [1 - θCL2 - BODY AREA × (body area - 1.62)] × e ηCL2i (L/h). V2 (peripheral compartment): (V2 )i = V2TV × [1 - θ V2-bodyarea × (bodyarea-1.62)] × e ηV2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and 0.515 L (39.1%), respectively. Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a significant effect on the CL1, and body surface area had a significant effect on the CL2 and the V2 (P < 0. 01).

CONCLUSIONSA good fit was derived for the PPK. The model could be used to provide guidance for MTX treatment and reduce adverse effects.

Adolescent ; Adult ; Child ; Female ; Humans ; Infusions, Intravenous ; Leucovorin ; administration & dosage ; therapeutic use ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Models, Molecular ; Osteosarcoma ; drug therapy ; Young Adult

Objective To study the impact of splenectomy and devascularization on liver function and liver fibrosis in patients with non-cirrhotic portal hypertension (NCPH). Methods The clinical data of patients with NCPH who were treated in Beijing You'an Hospital of Capital Medical University from April 2008 to December 2017 were retrospectively analyzed. The patients were divided into the observation group (n=16 ) and the control group ( n =30 ) according to their treatment methods. The observation group underwent splenectomy combined with devascularization, while the control group received conservative treatment. The changes in liver function, ascites, varicose vein rupture and bleeding before and after treat-ment, and the changes in liver blood flow before and after treatment in the observation group were compared. Results The before and after treatment of the 2 groups in ALT, AST, total bilirubin, albumin showed no statistically significant difference (P＞0. 05). Six months after treatment, the rates of ascites and bleeding were significantly higher than the observation group, (P＜0. 05). Ten patients who had a history of preoper-ative variceal hemorrhage in the observation group did not bleed within 6 months after treatment. Further-more, in the observation group after treatment when compared with the control group, the PC-Ⅲ [(32. 3 ± 12. 1) g/L vs. (56. 7 ± 15. 3)g/L],Ⅵ-C [(46. 6 ± 35. 0) g/L vs. (121. 3 ± 30. 4)g/L], LN [(32. 5 ± 10. 5) g/L vs. (65. 8 ± 11. 1) g/L] were significantly lower than the control group ( P ＜0. 05). The preoperative portal venous blood flow in the observation group was significantly higher than that after surgery [(1 056. 8 ± 679. 8) ml/min vs. (481. 0 ± 227. 6) ml/min, P＜0. 05]. Conclusion Splenectomy and devascularization effectively stopped variceal bleeding and delayed liver fibrosis in NCPH patients without affecting the liver function.

Objective:To investigate the role of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase (MMP)-2 in pancreatic tissue repair and reconstruction in rats with acute pancreatitis and its potential mechanism.Methods:114 male SD rats were randomly divided into normal control group (CON group) and acute edematous pancreatitis model group (AEP group), acute necrotic pancreatitis model group (ANP group), ANP control group and ANP intervention group. The rat AEP model was constructed by subcutaneous injection of caerulein, and the rat ANP model was prepared by intraperitoneal injection of L-arginine. The ANP intervention group and ANP control group were prepared by intraperitoneal injection of TGF-β1 inhibitor SB431542 or DMSO 30 min before, 24 h and 48 h after pancreatitis induction, respectively. Hydroxyproline content in pancreatic tissue was determined by hydroxyproline kit. The expression of TGF-β1, phosphorylated Smad3 (p-Smad3), type Ⅲ collagen and MMP-2 in pancreatic tissue was detected by immunohistochemical method. The activity of MMP-2 was determined by gelatin enzyme spectrometry. The expression levels of MMP-2 and p-Smad3 proteins in pancreatic tissue were detected by Western blot.Results:The hydroxyproline content in CON group was (61.71±8.56)μg/mg protein. The hydroxyproline content in AEP group reached the peak (116.72±8.53)μg/mg on the 3rd day. The peak value of hydroxyproline content in ANP group was (174.93±11.75)μg/mg on day 5. The peak value in ANP group was significantly higher than that in AEP group, and the peak value of hydroxyproline content in AEP group was significantly higher than that in CON group. The hydroxyproline content at day 3, 5 and 7 in the ANP intervention group was (108.07±10.48)μg/mg, (137.14±8.66)μg/mg and (112.35±13.16)μg/mg, respectively, and that at day 3, 5 and 7 in the ANP control group was (132.35±14.2)μg/mg, (175.43±13.75)μg/mg and (137.92±12.65)μg/mg, respectively. TGF-β1 immunohistochemical peak score in control group, AEP group and ANP group was (0.12±0.03), (1.96±0.21) and (3.00±0.28), respectively. p-Smad3 immunohistochemical peak score was (0.15±0.05), (2.05±0.20), and (3.05±0.24), while type Ⅲ collagen immunohistochemical peak score was (0.11±0.04), (1.56±0.15), and (3.10±0.17). MMP-2 immunohistochemical peak score was (0.05±0.03), (1.45±0.20), and (2.45±0.15), respectively. The immunohistochemical peak scores of TGF-β1, p-Smad3, type Ⅲ collagen and MMP-2 in ANP group were significantly higher than those in AEP group. The immunohistochemical peak scores of TGF-β1, p-Smad3, type Ⅲ collagen and MMP-2 in pancreatic tissue of ANP intervention group and ANP control group were (2.36±0.21), (2.25±0.22), (2.47±0.19), (2.00±0.10) and (3.02±0.21), (3.01±0.19), (3.05±0.24), (2.43±0.11), respectively, which in ANP intervention group was significantly lower than those in the ANP control group. The peak value of MMP-2 activity in pancreatic tissue of CON group, AEP group and ANP group was (10.85±1.73), (85.78±7.16) and (115.43±8.7), respectively, which in ANP group was significantly higher than that in AEP group, and in AEP group was significantly higher than that in CON group. In ANP intervention group and ANP control group 3 and 5 days after molding, the expression levels of MMP-2 protein in pancreas were 0.20±0.01, 1.19±0.02, 0.52±0.01, 1.54±0.05, respectively; p-Smad3 protein expression levels were 0.30±0.04, 0.66±0.11, 1.95±0.05, 1.30±0.01, respectively; and MMP-2 and p-Smad3 in ANP intervention group was significantly lower than those the ANP control group. All the differences among the groups above were statistically significant (all P value <0.001). Conclusions:TGF-β1 and MMP-2 play an important role in tissue remodeling and extracellular matrix deposition after acute pancreatitis inflammation.

Objective Establishment and evaluation of a mouse model of aldosterone-induced multi-organ damage.Methods Twenty mice were randomly divided into four groups,with five mice in each group:a blank control group(0 μg/(kg·d)),a low-dose aldosterone group(150 μg/(kg·d))),a medium-dose aldosterone group(300 μg/(kg d)),and a high-dose aldosterone group(450 pug/(kg·d)).Aldosterone-containing osmotic minipumps were surgically implanted under the skin,and aldosterone was infused for 4 weeks to establish the aldosterone-induced damage model.The body weight and blood pressure of the mice were recorded weekly.After the 4 week modeling period,the mice were euthanized,and their tissues were collected for observation and analysis of blood pressure and histological morphology of various organs.Results(1)After 4 weeks of aldosterone infusion,the serum aldosterone levels were significantly increased in the medium-dose and high-dose aldosterone groups,but not in the low-dose aldosterone group.(2)After the implantation of osmotic minipumps,the systolic blood pressure was significantly increased in the low-dose,medium-dose,and high-dose aldosterone groups during the second and third weeks,but decreased in all these groups during the fourth week.(3)The kidney and heart in the low-dose,medium-dose,and high-dose aldosterone groups showed varying degrees of damage,interstitial edema,collagen deposition,and fibrotic lesions.The liver in the low-dose aldosterone group showed a small amount of collagen deposition,while the medium-dose and high-dose aldosterone groups showed varying degrees of hepatocyte damage,collagen deposition,and fibrotic lesions.Conclusions Aldosterone can induce multi-organ damage in mice.Under this modeling method,organ damage is mainly manifested as edema,collagen deposition,and fibrotic lesions.

Objective To evaluate the efficacy of endoscopic ultrasound guided biliary drainage (EUS-BD) in patients with biliary obstruction and surgically altered anatomies.Methods We collected data from 33 patients with biliary obstruction and surgically altered anatomies from January 2016 to January 2018 in Zhejiang University School of Medicine Affiliated Hangzhou First People's Hospital who underwent EUS-guided biliary drainage after unsuccessful ERCP.The operation success rate,clinical success rate,complication rate,hospital stay were studied.Results Of 33 patients,31 were successfully operated and stented using endoscopic ultrasound puncture:14 patients through the stomach,17 patients through the duodenum;8 patients by the rendezvous approach.The operation success rate was 93.9％.Of the 33 patients,28 had a significant decrease in jaundice,with a clinical success rate of 84.9％.Complications consisted of 2 patients with bleeding and 1 patient with cholangitis.These patients improved after conservative treatment.The complications rate was 9.1％.The hospital stay was (12.4±5.7) d.Conclusion EUS-BD can be the first choice for patients with biliary obstruction and surgically altered anatomy after failed endoscopic retrograde cholangiograohv in centers with exoertise in EUS-BD procedures.