1.Expression and clinical significance of programmed cell death ligand 1in liver tissues of patients with chronic hepatitis B virus infection
Chengrun XU ; Xuesong LIANG ; Ruidan ZHENG ; Jiao YU ; Mobin WAN
Chinese Journal of Infectious Diseases 2011;29(5):282-285
Objective To investigate expressions of programmed cell death ligand 1 (PD-L1) in hepatic tissues at the different stages of hepatitis B virus ( HBV) infection, and clarify its role in the mechanism of chronic hepatitis B virus infection. Methods The expressions of PD-L1 were detected by immunohistochemistry and computer image quantitative analysis in the hepatic tissues of 65 chronic HBV infected patients and 5 healthy controls. The correlations between PD-L1 expression and inflammatory grading in the hepatic tissues, total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum HBV DNA level were analyzed. Results The PD-L1 expressions in hepatic tissues of HBV infection with G0 - G4 inflammatory grades were 3. 07 % ±0.93%, 8.01%±1.49%, 11.60%±2.60%, 18.41%±2.21% and 26. 04% ±3. 41%, respectively,which were all significantly stronger than that in controls (0. 64%±0. 28%). PD-L1 expression was a positively correlated with inflammation grading of hepatitis tissues, TBil, ALT and AST level in serum (r=0. 917, 0. 787, 0. 483, 0. 628; all P<0. 05), and negatively correlated with serum HBV DNA load (r=-0. 620, P<0. 05). Conclusion The upregulated PD-L1 expression may be probably involved in the chronicity of HBV infection.
2.Predictors for HBeAg negative chronic hepatitis patients with steatosis and its value in diagnosis of hepatic inflammation and fibrosis
Ruidan ZHENG ; Chengrun XU ; Jiarong MENG ; Minfeng ZHANG ; Aixia DOU ; Kun ZHOU ; Lungen LU
Chinese Journal of Digestion 2009;29(9):533-536
Objective To investigate the relationship between clinical presentation and pathological characteristics in HBeAg negative chronic hepatitis B(CHB) patients with steatosis, and to find out the predictors of hepatic inflammation and fibrosis. Methods HgeAg negative CHB patients with (n=56) or without (n=60) steatosis confirmed clinically and pathologically were enrolled in the study. All patients were examined for fasting blood glucose(FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyhransferase (GGT), alkaline phosphatase (ALP) albumin (Alb), globulin(Glb), homeostatic model assessment of insulin resistance (HOMA-IR), HBV-DNA and body mass index(BMI). The association of above parameters with hepatic inflammation, fibrosis and fatty deposition were analyzed statistically. Results It was demonstrated that BMI, FBG, FINS, TG, TC, GGT, ALP , Glb and HOMA-IR were significantly higher in HBeAg negative CHB patients with steatosis than those without steatosis (P<0.05). Whereas the levels of HBV-DNA, Alb, ALT and AST were significantly lower in HBeAg negative CHB patients with steatosis compared with those without steatosis (P<0.05). The hepatic inflammation and fibrosis were aggravated in patients with steatosis. It was implicated that BMI,FBG, FINS, TG, TC, GGT and HOMA-IR(all P values 0.05) were significant predictors for hepatic steatosis, while ALT, AST, Glb and HBV-DNA(all P values <0.05) were significant predictors for hepatic inflammation. And the predictors for hepatic fibrosis were ALT, AST, Alb, Glb and HBV-DNA(all P values <0.05). Conclusions Hepatic steatosis is common in HBeAg negative CHB patients which is positively associated with parameters including BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. Besides steatosis, the hepatic inflammation and fibrosis are also aggravated in these patients.
3.Preparation and preliminary biological evaluation of domestic 177Lu-PSMA-617
Xinyi ZHANG ; Wenhui FU ; Tingting XU ; Chengrun ZENG ; Yuxiao XIA ; Huipan LIU ; Lin CHEN ; Chi QI ; Yuchuan YANG ; Hongyuan WEI ; Yue CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(5):296-302
Objective:To synthesize 177Lu-prostate-specific membrane antigen (PSMA)-617 with domestic 177Lu (made in China), and explore its optimal labeling condition, biodistribution, stability, and safety. Methods:177Lu-PSMA-617 was prepared with domestic 177Lu by a manual method. The optimal labeling condition, radiochemical purity, stability ( in vivo and in vitro), lipid-water partition coefficient, and plasma protein binding rate were determined. The uptake rate of 177Lu-PSMA-617 was evaluated by using 22RV1 cells. Biodistribution and SPECT/CT imaging were performed on normal mice with imported 177Lu-PSMA-617 as control group. The blood routine test was performed to evaluate the safety. Results:The best labeling result of domestic 177Lu-PSMA-617 can be obtained under the following conditions: pH=4.5, 100 ℃ for 30 min. And the radiochemical purity was ≥99%. The product was stable in vivo and in vitro, with the radiochemical purity >95% in 72 h. The plasma protein binding rate was (35.3±5.3)%, the lipid-water partition coefficient was -2.27±0.06, and the specific uptake rate of domestic 177Lu-PSMA-617 by 22RV1 cells reached the highest in 1 h ((7.58±0.84)%), which was slightly lower than the imported 177Lu-PSMA-617 ((7.86±0.96)%), but there was no significant difference between them ( t=-0.439, P>0.05). The distribution and SPECT/CT imaging of normal mice showed that domestic and imported 177Lu-PSMA-617 in blood were cleared quite fast, and both of them were excreted mainly through the kidneys. No obvious adverse reactions were found in the toxicity test of domestic and imported 177Lu-PSMA-617. There was no obvious abnormality in blood routine and liver and kidney metabolism. Conclusion:The domestic 177Lu-PSMA-617 has many advantages, such as qualified quality control, good biological properties and safety, which support its potential application value in diagnosis of prostatic neoplasms.
4.Research progress of salivary glands injury secondary to 225Ac/ 177Lu-PSMA-617 in the treatment of prostate cancer and its protection
Wenhui FU ; Tingting XU ; Huipan LIU ; Xinyi ZHANG ; Chengrun ZENG ; Yue CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(10):628-632
Prostate specific membrane antigen (PSMA) radioligand therapy (RLT) is effective in metastatic castration-resistant prostate cancer (mCRPC). However, PSMA RLT can cause radiation damage to salivary glands, especially 225Ac/ 177Lu-PSMA-617. Radiation-related salivary glands damage can cause xerostomia, reduce the quality of life, and even limit the dose of radiopharmaceuticals and reduce the efficacy of tumor treatment. At present, there are few literatures on PSMA RLT related salivary glands damage in China. In this article, radiation-related salivary glands damage and the related protective measures during 225Ac/ 177Lu-PSMA-617 RLT are reviewed based on domestic and foreign studies.