1.Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway
Nuer AILI ; Qingyu CAO ; Huan LIU ; Junwei HE ; Weihong ZHONG ; Lan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):139-148
ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus (T2DM) rats and to explore its mechanism of action based on the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA high-fat diet and streptozotocin (STZ) were used to establish T2DM rat models. The rats were randomly assigned into six groups: the blank control group, model group, metformin group (300 mg·kg-1), and phlorizin high-dose (100 mg·kg-1) and low-dose groups (25 mg·kg-1). The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose (FBG) were observed, and the oral glucose tolerance test (OGTT) was carried out. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated serum protein (GSP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin (FINS), interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by the biochemical assays. The pancreas index, liver index, and insulin resistance index were calculated. Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β (GSK-3β) and forkhead box transcription factor O1 (FoxO1) proteins. ResultsCompared with the blank control group, the body weight of rats in the model group continued to decrease, while the FBG level increased significantly. The area under the OGTT blood glucose curve (AUC), GSP, TC, TG, LDL-C, IL-1β, IL-6, TNF-α, MDA, pancreatic index and liver index increased significantly, while the levels of HDL-C, SOD, and FINS decreased significantly (P0.05, P0.01). Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly (P0.01), while the glucagon-positive α-cells increased significantly (P0.01). Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly (P0.01), while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly (P0.01). Compared with the model group, the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC, GSP, TC, TG, LDL-C, MDA, IL-1β, IL-6, TNF-α and the pancreatic index, liver index were obviously reduced (P0.05, P0.01), while the levels of HDL-C, SOD, and FINS obviously increased (P0.05, P0.01). The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly (P0.01), while the glucagon-positive α-cells decreased significantly (P0.01). The protein expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 in the liver were significantly reduced (P0.01), while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased (P0.01). ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats, improved blood lipid profiles, oxidative stress, and inflammatory levels, alleviated insulin resistance, and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1, thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis, ultimately improving glycolipid metabolism disorders.
2.Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway
Nuer AILI ; Qingyu CAO ; Huan LIU ; Junwei HE ; Weihong ZHONG ; Lan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):139-148
ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus (T2DM) rats and to explore its mechanism of action based on the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA high-fat diet and streptozotocin (STZ) were used to establish T2DM rat models. The rats were randomly assigned into six groups: the blank control group, model group, metformin group (300 mg·kg-1), and phlorizin high-dose (100 mg·kg-1) and low-dose groups (25 mg·kg-1). The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose (FBG) were observed, and the oral glucose tolerance test (OGTT) was carried out. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated serum protein (GSP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin (FINS), interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by the biochemical assays. The pancreas index, liver index, and insulin resistance index were calculated. Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β (GSK-3β) and forkhead box transcription factor O1 (FoxO1) proteins. ResultsCompared with the blank control group, the body weight of rats in the model group continued to decrease, while the FBG level increased significantly. The area under the OGTT blood glucose curve (AUC), GSP, TC, TG, LDL-C, IL-1β, IL-6, TNF-α, MDA, pancreatic index and liver index increased significantly, while the levels of HDL-C, SOD, and FINS decreased significantly (P0.05, P0.01). Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly (P0.01), while the glucagon-positive α-cells increased significantly (P0.01). Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly (P0.01), while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly (P0.01). Compared with the model group, the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC, GSP, TC, TG, LDL-C, MDA, IL-1β, IL-6, TNF-α and the pancreatic index, liver index were obviously reduced (P0.05, P0.01), while the levels of HDL-C, SOD, and FINS obviously increased (P0.05, P0.01). The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly (P0.01), while the glucagon-positive α-cells decreased significantly (P0.01). The protein expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 in the liver were significantly reduced (P0.01), while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased (P0.01). ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats, improved blood lipid profiles, oxidative stress, and inflammatory levels, alleviated insulin resistance, and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1, thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis, ultimately improving glycolipid metabolism disorders.
3.Preparation and evaluation of PET tracer 18F-JR-1001 targeting cannabinoid type 1 receptor
Dilong MAO ; Yangyang XU ; Junwei CHEN ; Wanli HE ; Chentao JIN ; Xiaofen MA ; Hong ZHANG ; Yi WEI ; Shuxia CAO ; Qiaozhen CHEN ; Qinggang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(10):617-622
Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.
4.Development and characterization of 18F-SQKJ-2: a novel PET tracer for the diagnosis of fear memory disorders
Wanli HE ; Chenxin MA ; Xinghai CAO ; Junwei CHEN ; Yan GU ; Shuxia CAO ; Zhiqiang WANG ; Dilong MAO ; Qinggang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(11):672-677
Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.
5.Structural Design and Experimental Study of a New Aerodynamic Electric Hook
Cao LIU ; Junwei HUANG ; Haidong LIAO ; Jiale YUAN ; Yang XIE ; Jiafeng LIU ; Yong YING ; Xiangtai ZENG ; Cong LIAO
Chinese Journal of Minimally Invasive Surgery 2025;25(10):628-635
Objective To investigate the safety parameters of the air-powered electrocautery hook and its advantages in laparoscopic surgery.Methods In pressure trauma experiments,21 healthy New Zealand White Rabbits were randomly divided into three groups.In each group,three sites(liver,intestine,and kidney)were selected from each rabbit,and the air-powered electrocautery hook was used under laparoscopy to apply pressure and time gradients in a cross-combination manner.The three groups of experimental rabbits were dissected at three time points:immediately after application,3 d post-application,and 7 d post-application.Pathological sections were prepared from the corresponding treated sites,and the extent of injury was assessed.In rabbit renal capsule removal experiment,another 20 healthy New Zealand White Rabbits were randomly divided into 2 groups.Renal capsule removal was performed by using an air-powered electrosurgical hook and a conventional electrosurgical hook,respectively,to compare the two groups in terms of surgical time,intraoperative bleeding volume,intraoperative complications,and the number of times of wiping speculum.Results In pressure trauma experiment,except for the intestinal tract at 3 seconds(P=0.060),the histopathological scores under 0.3 MPa pressure were significantly higher than those under 0.1 MPa(P<0.05)and 0.2 MPa(P<0.05)in all the tissues.In the tissue sampling groups at 3 d and 7 d post-surgery,no tissue damage was observed in any tissue at any time point under 0.1 MPa pressure.In rabbit renal capsule removal experiment,the aerodynamic electrocautery group had less intraoperative bleeding volume than the conventional electrocautery group[(2.9±0.5)ml vs.(3.4±0.5)ml,t=-2.280,P=0.035].There were no significant differences between the two groups in terms of surgical time,intraoperative complication rates,and the number of times of wiping speculum(P>0.05).Conclusions The safe pressure range for using the air-powered electrosurgical hook on the surfaces of the kidney and intestinal tract is within 0.2 MPa.Within the safe pressure range,blowing on tissue for 6 seconds or less is relatively safe.Using the air-powered electrosurgical hook in surgeries requiring the separation of loose connective tissue can reduce intraoperative bleeding.
6.Structural Design and Experimental Study of a New Aerodynamic Electric Hook
Cao LIU ; Junwei HUANG ; Haidong LIAO ; Jiale YUAN ; Yang XIE ; Jiafeng LIU ; Yong YING ; Xiangtai ZENG ; Cong LIAO
Chinese Journal of Minimally Invasive Surgery 2025;25(10):628-635
Objective To investigate the safety parameters of the air-powered electrocautery hook and its advantages in laparoscopic surgery.Methods In pressure trauma experiments,21 healthy New Zealand White Rabbits were randomly divided into three groups.In each group,three sites(liver,intestine,and kidney)were selected from each rabbit,and the air-powered electrocautery hook was used under laparoscopy to apply pressure and time gradients in a cross-combination manner.The three groups of experimental rabbits were dissected at three time points:immediately after application,3 d post-application,and 7 d post-application.Pathological sections were prepared from the corresponding treated sites,and the extent of injury was assessed.In rabbit renal capsule removal experiment,another 20 healthy New Zealand White Rabbits were randomly divided into 2 groups.Renal capsule removal was performed by using an air-powered electrosurgical hook and a conventional electrosurgical hook,respectively,to compare the two groups in terms of surgical time,intraoperative bleeding volume,intraoperative complications,and the number of times of wiping speculum.Results In pressure trauma experiment,except for the intestinal tract at 3 seconds(P=0.060),the histopathological scores under 0.3 MPa pressure were significantly higher than those under 0.1 MPa(P<0.05)and 0.2 MPa(P<0.05)in all the tissues.In the tissue sampling groups at 3 d and 7 d post-surgery,no tissue damage was observed in any tissue at any time point under 0.1 MPa pressure.In rabbit renal capsule removal experiment,the aerodynamic electrocautery group had less intraoperative bleeding volume than the conventional electrocautery group[(2.9±0.5)ml vs.(3.4±0.5)ml,t=-2.280,P=0.035].There were no significant differences between the two groups in terms of surgical time,intraoperative complication rates,and the number of times of wiping speculum(P>0.05).Conclusions The safe pressure range for using the air-powered electrosurgical hook on the surfaces of the kidney and intestinal tract is within 0.2 MPa.Within the safe pressure range,blowing on tissue for 6 seconds or less is relatively safe.Using the air-powered electrosurgical hook in surgeries requiring the separation of loose connective tissue can reduce intraoperative bleeding.
7.Preparation and evaluation of PET tracer 18F-JR-1001 targeting cannabinoid type 1 receptor
Dilong MAO ; Yangyang XU ; Junwei CHEN ; Wanli HE ; Chentao JIN ; Xiaofen MA ; Hong ZHANG ; Yi WEI ; Shuxia CAO ; Qiaozhen CHEN ; Qinggang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(10):617-622
Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.
8.Development and characterization of 18F-SQKJ-2: a novel PET tracer for the diagnosis of fear memory disorders
Wanli HE ; Chenxin MA ; Xinghai CAO ; Junwei CHEN ; Yan GU ; Shuxia CAO ; Zhiqiang WANG ; Dilong MAO ; Qinggang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(11):672-677
Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.
9.Advances in animal models of sphincter of Oddi dysfunction
Haonan LIN ; Yixuan LIANG ; Wangqiang ZHAO ; Junwei CAO ; Tianqi WANG ; Zhuorui LIANG ; Changmiao WANG
Chinese Journal of Hepatobiliary Surgery 2024;30(6):476-480
Sphincter of Oddi dysfunction (SOD) refers to the abnormal physiological function of sphincter of Oddi, which causes a series of syndromes in biliary tract, pancreas and liver. At present, the related research of SOD is becoming a hot spot, but its pathogenesis is not clear. This article will review the domestic and international literatures on SOD, review the advantages and disadvantages of experimental animals such as rabbits, dogs and guinea pigs, and analyze the characteristics of drugs and surgical modeling, so as to provide references for future related model establishment.
10.Clinical application of iohexol plasma clearance assay for determination of glomerular filtration rate in chronic kidney disease
Jing LIU ; Lulu WANG ; Lei JIANG ; Junwei YANG ; Hongdi CAO
Chinese Journal of Nephrology 2024;40(5):358-366
Objective:To evaluate the clinical application value of iohexol plasma clearance assay in assessing glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), and identify alternative methods of 99mTc-diethylene triamine pentaacetic acid renal kinetic imaging (Gates) method for measuring GFR ( 99mTc-mGFR). Methods:It was a cross-sectional study. The CKD patients hospitalized in the Department of Nephrology at the Second Affiliated Hospital of Nanjing Medical University between October 2022 and September 2023 were enrolled. Iohexol plasma clearance was determined by collecting blood samples at 2 and 4 hours after intravenous administration of 5 ml iohexol, and high performance liquid chromatography was used to measure the plasma concentration of iohexol. Br?chner-Mortensen and Jacobsson formulas were used to calculate the double and single plasma iohexol clearance, respectively. CKD-epidemiology collaboration equation based on serum creatinine concentration was used to calculate the estimated GFR (eGFR). Pearson's coefficient was performed to analyze the correlation of iohexol dual plasma clearance assay-measured GFR (iohexol-DS-mGFR), iohexol single plasma 4 hours clearance assay-measured GFR (iohexol-SS 4h-mGFR), iohexol single plasma 2 hours clearance assay-measured GFR (iohexol-SS 2h-mGFR) and eGFR with 99mTc-mGFR as the gold standard. Bland-Altman analysis, 95% limits of agreement, and intra-correlation coefficient were used to compare the diagnostic concordance of Iohexol-DS-mGFR, Iohexol-SS 4h-mGFR, Iohexol-SS 2h-mGFR and eGFR with 99mTc-mGFR. Results:The study enrolled 64 CKD patients, aged (58.91±13.08) years old, comprising of 38 males and 26 females. The distribution of patients across CKD stages based on 99Tc-mGFR was as follows: 12 patients (18.8%) in stage 1, 14 patients (21.9%) in stage 2, 26 patients (40.6%) in stage 3, 10 patients (15.6%) in stage 4, and 2 patients (3.1%) in stage 5. The Pearson correlation analysis revealed that the correlation coefficients of iohexol-DS-mGFR, iohexol-SS 4h-mGFR, iohexol-SS 2h-mGFR and eGFR with 99mTc-mGFR were 0.925, 0.867, 0.820 and 0.894 (all P<0.001), respectively. The median deviation of absolute value of iohexol-DS-mGFR, iohexol-SS 4h-mGFR, iohexol-SS 2h-mGFR and eGFR in the total study population were 6.66, 9.63, 11.47 and 9.59 ml·min -1·(1.73 m 2) -1, respectively. The proportions of iohexol-DS-mGFR, iohexol-SS 4h-mGFR, iohexol-SS 2h-mGFR and eGFR located in the gold-standard GFR ± 10% interval (P10) were 35.9%, 29.7%, 26.6% and 29.7%, respectively, and the proportions located in the gold-standard GFR ± 30% interval ( P30 ) were 87.5%, 68.8%, 60.9% and 73.4%, respectively. Conclusions:Iohexol dual plasma clearance is well correlated and consistent with 99mTc-mGFR. It is a safe and easy alternative to isotope 99mTc-mGFR for clinical use in determining GFR.

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