ABSTRACT
The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1 were administered to chondrocytes. Micro-CT scanning and histological observations were conducted on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IB, which further reduced the downstream phosphorylation of P65 in nuclear factor-B (NF-B) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1-induced chondrocyte damage. , Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.
ABSTRACT
Objective To investigate the risk factors resulting in the perioperative liver failure and death for the HBV-associated hepatocellular carcinoma (HCC) patients with or without cirrhosis.Methods The method of retrospective case-control study was performed.The clinicopathological data of 1 083 HCC patients with positive HBsAg who received curative liver resection at the Southwest Hospital from January 2008 to December 2012 were collected.According to the absence or presence of cirrhosis,the HCC patients with positive HBsAg were divided into the 2 groups,including the cirrhosis group (633 patients) and the non-cirrhosis group (450patients).The intraoperative conditions (operation time,volume of intraoperative blood loss,rate of blood transfusion,rate of pringle maneuver) and postoperative conditions (incidence of perioperative complications,duration of postoperative hospital stay,perioperative mortality) of HCC patients were observed.The gender,age,alanine transaminase (ALT),aspartate transaminase (AST),albumin (Alb),total bilirubin (TBil),platelet (PLT),Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,pringle maneuver,extent of liver resection,number of tumors,tumor diameter,tumor thrombus and liver cirrhosis were enrolled and prognostic factors resulting in perioperative liver failure and death for the HCC patients were explored.Measurement data with skewed distribution were presented as M (range) and comparison between the 2 groups was analyzed using Mann-Whitney U test.Count data were presented as counts (percentage) and comparison between the 2 groups was analyzed using chi-square test or Fisher exact probability.Univariate analysis was performed by chi-square test and multivariate analysis was performed by Logistic regression model (forward).Results (1) The intraoperative conditions:the volume of intraoperative blood loss were 500 mL (range,30-7 000 mL) in the cirrhosis group and 400 mL (range,50-8 000 mL) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-2.209,P ＜ 0.05).The operation time,rate of blood transfusion and rate of pringle maneuver were 250 minutes (range,82-715 minutes),29.86％ (189/633),62.24％ (394/633) in the cirrhosis group and 242 minutes (range,85-738 minutes),27.11％ (122/450),66.67％ (300/450) in the non-cirrhosis group,respectively,with no statistical differences between the 2 groups (Z =-1.212,x2 =0.969,2.236,P ＞0.05).(2) The postoperative conditions:the incidence of perioperative complications was 30.49％(193/633) in the cirrhosis group and 21.11％ (95/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2 =11.851,P ＜ 0.05).The incidence of lung infection,abdominal infection and liver failure were 6.48％ (41/633),2.69％ (17/633),5.53％ (35/633) in the cirrhosis group and 3.56％ (16/450),0.89％ (4/450),1.33％ (6/450) in the non-cirrhosis group,respectively,with statistically significant differences between the 2 groups (x2 =4.502,4.465,12.713,P ＜ 0.05).The duration of postoperative hospital stay was 15 days (range,0-70 days) in the cirrhosis group and 14 days (range,0-71 days) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-3.448,P ＜ 0.05).The perioperative mortality was 5.85％ (37/633) in the cirrhosis group and 2.44％ (11/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2=7.181,P ＜ 0.05).(3)Results of risk factors affecting perioperative liver failure:①results of univariate analysis showed that age,AST,Alb,Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,extent of liver resection,tumor diameter,liver cirrhosis with positive HBsAg were associated with perioperative liver failure in HCC patients (x2=5.013,7.979,8.855,16.968,14.148,9.764,18.511,11.749,5.534,12.713,P＜0.05);age,AST,Alb,Child-Pugh classification,operation time,blood transfusion,extent of liver resection and tumor diameter were associated with perioperative liver failure in the cirrhosis group (x2=5.877,5.380,11.087,13.672,8.849,13.170,12.418,5.805,P ＜ 0.05);volume of intraoperative blood loss was associated with perioperative liver failure in the non-cirrhosis group (P ＜ 0.05).②Results of multivariate analysis showed that age≥60 years,Child-Pugh class B,operation time ＞ 360 minutes,blood transfusion,extent of liver resection ≥3 segments and liver cirrhosis were independent risk factors affecting perioperative liver failure in HCC patients with positive HBsAg [OR =2.285,2.716,2.315,2.159,2.459,4.322;95％ confidence interval (CI):1.081-4.831,1.100-6.706,1.064-5.038,1.068-4.362,1.264-9.786,1.763-10.598,P＜0.05];Alb ＜38 g/L,Child-Pugh class B,blood transfusion and extent of liver resection ≥ 3 segments were independent risk factors affecting perioperative liver failure in the cirrhosis group (OR =2.231,2.857,2.186,2.927,95％ CI:1.038-4.795,1.095-7.451,1.045-4.576,1.426-6.008,P ＜ 0.05);volume of intraoperative blood loss ＞ 1 200 mL was an independent risk factor affecting perioperative liver failure in the non-cirrhosis group (OR =15.077,95％CI:2.695-84.353,P ＜ 0.05).(4) Risk factors affecting perioperative death:①results of univariate analysis showed that gender,Alb,TBil,Child-Pugh classification,blood transfusion,extent of liver resection,tumor diameter,tumor thrombus and liver cirrhosis were associated with perioperative death in HCC patients with positive H BsAg (x2=4.462,8.783,4.212,4.869,7.189,11.745,6.837,4.323,7.181,P ＜0.05);Alb,extent of liver resection and tumor diameter were associated with perioperative death in the cirrhosis group (x2=12.173,12.793,10.981,P ＜ 0.05);blood transfusion and tumor thrombus were associated with perioperative death in the non-cirrhosis group (x2 =5.836,6.417,P ＜ 0.05).② Results of multivariate analysis showed that Alb ＜38 g/L,extent of liver resection ≥ 3 segments and liver cirrhosis were independent risk factors affecting perioperative death in HCC patients with positive HBsAg (OR =2.560,2.657,2.567,95％ CI:1.382-4.742,1.471-4.800,1.283-5.134,P ＜ 0.05);Alb ＜ 38 g/L,extent of liver resection ≥ 3 segments and tumor diameter≥5 cm were independent risk factors affecting perioperative death in the cirrhosis group (OR =3.003,2.533,3.060,95％ CI:1.495-6.034,1.251-5.128,1.135-8.251,P＜0.05);blood transfusion and tumor thrombus were independent risk factors affecting perioperative death in the non-cirrhosis group (OR =3.755,4.036,95％ CI:1.047-13.467,1.126-14.469,P ＜ 0.05).Conclusions Liver cirrhosis is an independent risk factor for perioperative liver failure and death in HCC patients with positive HBsAg.The risk of perioperative liver failure and death in HCC patients with cirrhosis is significantly higher than that in HCC patients without cirrhosis,and there is a difference in the risk factors for perioperative liver failure and death.