1.Sulfasalazine relieves cholestatic liver injury by activating peroxisome proliferator-activated receptor-α
Jing XU ; Xuan WANG ; Yu ZHANG ; Jing XIAO ; Hang YOU ; Zongyi LIU ; Yong SUN ; Yinghua LAN ; Hong REN ; Chungang LIU ; Mingli PENG
Chinese Journal of Hepatology 2025;33(5):448-455
Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.
2.Sulfasalazine relieves cholestatic liver injury by activating peroxisome proliferator-activated receptor-α
Jing XU ; Xuan WANG ; Yu ZHANG ; Jing XIAO ; Hang YOU ; Zongyi LIU ; Yong SUN ; Yinghua LAN ; Hong REN ; Chungang LIU ; Mingli PENG
Chinese Journal of Hepatology 2025;33(5):448-455
Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.
3.Test-retest reliability analysis of MRI criteria in the 2019 Bosniak classification of cystic renal masses
Xu BAI ; Songmei SUN ; Huanhuan KANG ; Lin LI ; Wei XU ; Chungang ZHAO ; Yongnan PIAO ; Ying WANG ; Xiaona WANG ; Meiyan YU ; Meifeng WANG ; Kaiqiang JIA ; Aitao GUO ; Huiyi YE ; Haiyi WANG
Chinese Journal of Radiology 2022;56(10):1121-1128
Objective:To evaluate the test-retest reliability of MRI criteria in the 2019 Bosniak classification of cystic renal masses (CRMs) and to analyze the impact of lesions′ property, size and readers′ experience on the test-retest reliability.Methods:From January 2009 to June 2019, 207 patients with 207 CRMs were included in this retrospective study. All of them underwent renal MRI and surgical-pathologic examination. According to Bosniak classification, version 2019, all CRMs were independently classified twice by eight radiologists with different levels of experience. All radiologists were blinded to the pathology of the lesions. By using intraclass correlation coefficient (ICC), test-retest reliability was evaluated for all CRMs and for subgroups with different pathological properties (benign and malignant) and different sizes (≤40 mm and>40 mm). The test-retest reliability of 4 senior readers (≥10 years of experience) and 4 junior readers (<10 years of experience) were evaluated respectively. The comparison of ICC was performed using Z test. Results:The 207 CRMs included 111 benign lesions (83 benign cysts, 28 benign tumors) and 96 malignant tumors. There were 87 lesions with maximum diameter ≤40 mm and 120 with maximum diameter>40 mm. The test-retest reliability (ICC) of each reader for all lesions was 0.776-0.888, the overall ICC was 0.848 (95%CI 0.821-0.872). The ICCs of senior and junior readers were 0.853 (95%CI 0.824-0.880) and 0.843 (95%CI 0.811-0.871) respectively, without significant difference between the two groups ( Z=0.85, P=0.374). The ICC of all readers was 0.827 for benign lesions and 0.654 for malignant lesions, showing significant difference ( Z=2.80, P=0.005). The ICC was 0.770 for lesions ≤40 mm and 0.876 for lesions>40 mm, which was significantly different ( Z=-2.36, P=0.018). For CRM subgroups with different pathological properties and different sizes, there was no significant difference in test-retest reliability between senior and junior readers (all P>0.05). Conclusion:The test-retest reliability of MRI criteria in the 2019 Bosniak classification of CRMs is excellent and unaffected by readers′ experience. The reliabilities are not consistent among CRMs of different pathological properties and different sizes, but all reached the level of good and above.
4.Investigation in vitro Release Rate and in vivo Pharmacokinetics of Resveratrol/Hydroxypropyl- β-Cyclodextrin/Chitosan Sustained-release Pellets in Rats
Chenchen YU ; Chungang ZHANG ; Li YIN ; Yixuan ZHOU ; Lan CHENG ; Tingguo KANG
China Pharmacy 2019;30(19):2603-2607
OBJECTIVE: To investigate in vitro release rate and in vivo pharmacokinetics of Resveratrol/hydroxypropyl-β- cyclodextrin/chitosan sustained-release pellets (RES/HP-β-CD/Chitosan) in rats. METHODS: In vitro release rate of RES raw materials, RES-HP-β-CD complexes (RES/HP-β-CD) and RES/HP-β-CD/Chitosan in water within 12 h were investigated by paddle method. The pharmacokinetic characteristics of RES raw materials, RES/HP-β-CD and RES/HP-β-CD/Chitosan were compared within 720 min after intragastric administration. RESULTS: Compared with RES raw materials, in vitro release rate of RES/HP-β-CD was increased significantly, and 120 min accumulative release rate reached 87%. Compared with RES/HP-β-CD, in vitro release rate of RES/HP-β-CD/Chitosan were relieved significantly; release time prolonged significantly; 12 h accumulative release rate was 72%. The pharmacokinetic parameters of RES raw materials, RES/HP-β-CD and RES/HP-β-CD/Chitosan included that cmax were 473.3, 2 492.2, 590.5 ng/mL; t1/2 were 2.6, 0.5, 4.6 h; AUC0-12 h were 514.7, 824.6, 2 778.5 ng·h/mL. Compared with RES raw materials, relative bioavailability of RES/HP-β-CD and RES/HP-β-CD/Chitosan were 172.5% and 540.0%. CONCLUSIONS: RES/HP-β-CD/Chitosan shows good sustained-release effect, and its bioavailability is significantly higher than that of RES raw materials, RES/HP-β-CD.
5.Preparation and Quality Evaluation of Resveratrol-Hydroxypropyl- β-Cyclodextrin-Chitosan Sustained-release Pellets
Chungang ZHANG ; Chenchen YU ; Yixuan ZHOU ; Li YIN ; Lan CHENG ; Tingguo KANG ; Lan HAN
China Pharmacy 2019;30(17):2322-2326
OBJECTIVE: To prepare Resveratrol-hydroxypropyl-β-cyclodextrin-chitosan sustained-release pellets (RES-HP-β- CD-Chitosan), and to characterize it. METHODS: Resveratrol raw material, HP-β-cyclodextrin and chitosan were collected with ratio of 1 ∶ 7 ∶ 0.25. Resveratrol-HP-β-cyclodextrin inclusion compound were prepared by solvent method, and then added into chitosan, RES-HP-β-CD-Chitosan were prepared by spray drying method. Particle size of prepared sustained-released pellets were observed by optical microscope. X-ray, DSC, IR and SEM were used to characterize RES-HP-β-CD-Chitosan. The contents of resveratrol in prepared sustained-released pellets were determined by UV spectrum, and drug-loading amount and encapsulation efficiency were calculated. RESULTS: Particle size of prepared RES-HP-β-CD-Chitosan was (2.23±0.35) μm (n=300). Characterization results show that RES-HP-β-CD-Chitosan was spherical in shape; shrinkage was found on the surface of microspheres, and resveratrol was included in HP-β-cyclodextrin in molecule or amorphous state. Drug-loading amount of prepared RES-HP-β-CD-Chitosan was 11.67% (n=3), encapsulation efficiency was 96.27% (n=3). CONCLUSIONS: RES-HP-β-CD- Chitosan is prepared successfully.
7.Comparison of the Standard Threshold Shift Criteria for Evaluating Hearing Conservation Programs.
Chang Sun SIM ; Kyoung Sook JEONG ; Yu Jung KIM ; Na Ri CHOY ; Choong Ryeol LEE ; Hun LEE ; Jong Pil JUNG ; Ok Hyun KIM ; Yo Weon LEE ; Seung Rim YANG ; Sung Soo OH ; Ji Ho LEE
Korean Journal of Occupational and Environmental Medicine 2006;18(3):179-188
OBJECTIVES: Workers from a factory was selected to compare 8 standard threshold shift criteria with the Korean diagnostic criteria of noise-induced hearing loss for this cohort study. METHODS: From 1990 to 1999, 491 workers at a manufacturing company with complete record of the hearing test covering the range of 0.5~6 kHz for 10 consecutive years were finally selected. Eight standard threshold shift criteria (15 dB once, NIOSH (1972), 10 dB average 3~4 kHz, OSHA STS, AAOHNS, 15 dB twice, 15 dB 1~4 kHz, OSHA STS twice) along with the Korean standard for diagnosing the noise-induced hearing loss (the average hearing threshold at 0.5, 1 and 2 kHz) were compared to calculate the degree of the threshold shift and the minimum time required to detect the change. RESULTS: Those workers showing at least one positive shift in the 'once'criteria of NIOSH (1972) were 92.5%; the 'average'criteria of 10 dB average 3~4 kHz were 35.8%; 'twice'criteria of 15 dB twice were 44.4%. The duration from the baseline to the year showing the first positive shift was from 3.2 +/- 3.1 years (NIOSH, 1972) to 6.0 +/- 2.1 years (OSHA STS twice). The percentage of true positive shift ranging from 20.4% (AAO-HNS) to 69.8% (NIOSH, 1972). There were 10 (2%) which met the Korean diagnostic criteria of noise-induced hearing loss. CONCLUSIONS: Currently the concept of hearing threshold shift in diagnosing the hearing loss was adopted in Korea thus in this study we determined the validity and the effect of the various hearing threshold shift criteria and showed that NIOSH (1972) criteria was the best of all. In the future, hearing data from various manufacturing workers should be compared to thoroughly evaluate the threshold shift criteria and to establish adequate standard for Korean workers.
Cohort Studies
;
Hearing Loss
;
Hearing Loss, Noise-Induced
;
Hearing Tests
;
Hearing*
;
Korea
;
National Institute for Occupational Safety and Health (U.S.)
;
United States Occupational Safety and Health Administration
8.A Survey of Food and Nutrient Intakes of Korean Men by Age Groups.
Lilha LEE ; Choon Hie YU ; Sang Sun LEE ; Moon Jeong CHANG ; Sun Hee KIM
The Korean Journal of Nutrition 2004;37(2):143-152
A dietary survey was conducted using 24-hour recall method in 80 male elementary school children, 83 high school students, 87 adults and 98 elderly people over 65 years of age to discuss food and nutrient intakes among different age groups. In observing food intake by age groups, the percentage of plant foods to total food intake was significantly higher in the elderly than other groups and that of animal foods was the highest in the children. The children consumed significantly higher amounts of milk and dairy products. Carbohydrate energy percent in the elderly people was 68.0%, significantly higher than other age groups. All age groups consumed Ca below Korean RDA and especially, 65.1% of the adolescents and 68.4% of the elderly consumed below 75% of RDA. Nutrient adequacy ratio (NAR) of most nutrients was lowest in the elderly. Mean adequacy ratio (MAR), an index of overall dietary quality, was 0.94 for the children, 0.84 for the adolescents, 0.84 for the adults, and 0.73 for the elderly. The above results suggest that food and nutrient intakes have been differently affected with advancing age, and overall dietary quality of the elderly people is lower than that of other age groups.
Adolescent
;
Adult
;
Aged
;
Animals
;
Child
;
Dairy Products
;
Eating
;
Humans
;
Male
;
Milk
;
Plants
9.Survival Analysis in Patients Starting Hemodialysis in Advanced Age: What and How Differs?.
Korean Journal of Nephrology 2003;22(2):161-164
No abstract available.
Humans
;
Renal Dialysis*
;
Survival Analysis*
10.Correction of Incidentally Migrated Pigtail Stent in Pancreatic Pseudocyst using Polypectomy Snare.
Ju Hyun KIM ; Dong Hoon KANG ; Hyun Chul PARK ; Jong Jae PARK ; Dong Kyun PARK ; Hyung Seon YUN ; Sun Suk KIM ; Yu Kyung KIM ; Duck Joo CHOI
Korean Journal of Gastrointestinal Endoscopy 1999;19(2):318-321
Endoscopic drainage of pancreatic pseudocysts is a new nonsurgical treatment modality. Among the cystogastrostomy and stent related complications, proximal migration of stent is rare and the correction of inserted stent into a pseudocyst is very difficult. We report a correction of an incidentally inserted pigtail stent into pseudocyst using a polypectomy snare.
Drainage
;
Pancreatic Pseudocyst*
;
SNARE Proteins*
;
Stents*

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