Table of Content

Volume 27 Issue 1
26 January 2022

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Paricalcitol attenuates intestinal ischemia-reperfusion injury in mice through HMGB1/TLR4/NF-κB signaling pathway

WU Lin, HAO Yingxiang, ZHANG Lei, ZHANG Tianxue, GAO Mingjing, LENG Yufang

2022, 27(1):  1-7.  doi:10.12092/j.issn.1009-2501.2022.01.001

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AIM: To observe the effect of paricalcitol on intestinal ischemia-reperfusion injury, and to explore the relationship with HMGB1/TLR4/NF-κB signaling pathway.  METHODS: Twenty-four SPF-grade healthy adult male C57BL/6J mice were divided into 4 groups (n=6) by random number table: sham operation group (S group), paricalcitol pretreatment+sham operation group (SP group), intestinal ischemia-reperfusion group (IR group) and paricalcitol ischemic preconditioning group (P group). S group and SP group were separated the superior mesenteric artery, IR group and P group were clamped the superior mesenteric artery for 45 minutes and then followed by reperfusion for 2 hours to establish the intestinal ischemia-reperfusion model; SP group and P group were intraperitoneally injected with 0.3 μg/kg paricalcitol 24 hours before surgery, and the other two groups were given equal volume of normal saline. The mice were sacrificed at 2 h after reperfusion, and the intestinal tissue was obtained 5 cm from the terminal ileum. The pathological results were observed under light microscope. The intestinal mucosal injury was scored according to the Chiu's scoring standard. The intestinal tissue diamine oxidase (DAO) and tumor were detected by ELISA. Necrosis factor α (TNF-α) and interleukin 6 (IL-6) content; Western blot was used to detect the expression levels of HMGB1, TLR4 and NF-κB p65 protein in small intestine tissues.RESULTS: Compared with S group and SP group, Chiu's score was increased, the expression of Dao, TNF-α and IL-6 were increased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein increased significantly in IR group (P<0.05); Compared with IR group, Chiu's score was decreased, the expression of Dao, TNF-α and IL-6 were decreased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein decreased significantly in P group (P<0.05). CONCLUSION: Paricalcitol can alleviate intestinal ischemia-reperfusion injury by inhibiting HMGB1/TLR4/NF-κB signaling pathway and playing an anti-inflammatory role.

Tianma Gouteng Yin protects rotenone-induced PC12 cell damage by inhibiting ferroptosis-lipid metabolism

GUO Yuting, LI Shanshan, LI Qinglin

2022, 27(1):  8-14.  doi:10.12092/j.issn.1009-2501.2022.01.002

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AIM: To investigate the effects and protective mechanism of Tianma Gouteng (TGY) against rotenone (Rot) damage in PC12 cells. METHODS: PC12 cells were treated with Rot to establish nerve injury model and cell survival rate was determined by MTT colorimetry to determine the optimal modeling concentration of Rot and effective intervention concentration of TGY. Lipid reactive oxygen species (ROS) were detected by flow cytometry and fluorescence intensity was observed by inverted fluorescence microscope. The biochemical methods were used to detect, superoxide dismutase (SOD), glutathione (GSH) levels and activity and the contents of malondialdehyde (MDA). Transmission electron microscopy observed morphological change of mitochondria and protein expression of glutathione peroxidase 4 (GPX4), long chain lipoyl-coa synthase 4 (ACSL4) and lysophospholipid cholinyltransferase 3 (LPCAT3) were detected by western blot. RESULTS: The survival rate of cells treated with 0.6 μmol/L Rot for 24 h was close to 50%(56.7%±9.9%). Pretreatment with TGY for 12 h could inhibit the damage of Rot. At the same time, the leakage rate of lactate dehydrogenase (LDH) was reduced in a dose-dependent manner. Lipid ROS content increased after the treatment of Rot, whereas pretreatment with TGY effectively reduced lipid ROS content, decreased MDA level and increased SOD activity and GSH level in damaged cells in cells damaged by Rot. Transmission electron microscopy showed that the mitochondria of PC12 cells were shrunk after the damage of 0.6 μmol/L Rot and the mitochondrial morphology of PC12 cells was improved to some extent after preprotection of TGY compared with normal group. Western blot results showed that TGY pretreatment could increase the expression of GPX4 and reduce the expression of ACSL4 and LPCAT3 after damage of Rot to a certain extent. CONCLUSION: TGY can improve nerve damage by up-regulating the expression of GPX4 protein, down-regulating the expression of ACSL4 and LPCAT3 protein to inhibit the oxidation of unsaturated fatty acids, reduce the level of lipid peroxidation and ROS content.

Trigliptin succinate have an effect on gut microbiota of type 2 diabetic mice

CHEN Qian, WANG Yafeng, DUO Delong, CHANG Ya'e, YAN Yingjun, DUAN Kunkun

2022, 27(1):  15-24.  doi:10.12092/j.issn.1009-2501.2022.01.003

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AIM: To study the effects of trigliptin succinate on gut microbiota of type 2 diabetic mice.  METHODS: 16S rRNA high-throughput sequencing method was used to sequence the intestinal flora of mice in the healthy group, the T2DM group, the trigliptin succinate group and the sitagliptin phosphate group. QIME was used to filter the data, classify and annotate the species. Alpha diversity index and Beta diversity index of the samples were analyzed.The richness and diversity of bacteria in the four groups were compared. RESULTS: The gut microbiota structure of mice in the healthy group, the T2DM group, the trigliptin succinate group and the setagliptin phosphate group were significantly different. The results showed that the ratio of Firmicutes to Bacteroidetes was decreased compared with that in the healthy group. Cyanobacteria, Verrucomicrobia and Tenericutes had significant differences (P<0.05). Potential biomarkers for T2DM group were Bacilli, Lactobacillales, Lactococcus and Streptococcaceae. Candidate biomarkers of trigliptin succinate group may be Bacteroidia, Bacteroidetes, Bacteroidales, Prevotella, Paraprevotellaceae, Parabacteroides, Porphyromonadaceae; The candidate biomarkers of sitagliptin phosphate group may be Lactobacillus, Lactobacillaceae and Helicobacter. CONCLUSION: The intestinal flora of mice in the trigliptin succinate group was significantly different from that in the healthy group and the T2DM group. Using trigliptin succinate to improve the intestinal flora of mice might achieve the hypoglycemic effect by improving the intestinal flora.

Effects of different administration methods on the pharmacokinetics and tissue distribution of ribavirin in rats

GUO Lu, ZHONG Zhendong, HAN Yicen, SHI Yi, YANG Yong, BIAN Yuan, LIU Xiaoshu, ZHANG Jing, LANG Qin, ZHONG Tian

2022, 27(1):  25-32.  doi:10.12092/j.issn.1009-2501.2022.01.004

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AIM: To establish a HPLCQqQMS with multiple reaction monitoring (MRM) method for pharmacokinetics and tissue distribution study of ribavirin by oral and respiratory administration.  METHODS: The experiment established a highsensitivity LCMS analytical method for the detection of ribavirin, and the linearity, specificity, recovery, accuracy, and precision were investigated. The established methods were used to investigate the pharmacokinetics and tissue distribution of the oral and respiratory administration methods. RESULTS: The concentration of drugs in the blood through respiratory tract administration is higher, and the drug absorption is faster. Respiratory tract administration Cmax(46.1±10.6) μg/L and AUC(0t)(276±68) μg·L1·h are significantly higher than oral administration Cmax(8.9±3.8) μg/L and AUC(0t)(142±63) μg·L1·h. The tissue distribution results showed that the content of ribavirin in lung tissue of respiratory tract administration was significantly higher than that of oral administration, and the metabolism time was longer.CONCLUSION: Compared with oral administration, respiratory tract administration has higher blood drug concentration and higher content in lung tissue, revealing the tissue targeting effect of inhaled administration. The HPLCQqQMS detection method is simple, effective, accurate, and reproducible, which can be applied to the determination of ribavirin in rat plasma and tissue.

Comparison of Bayesian method and multiple linear regression method in predicting warfarin dose model

WEN Dusu, WANG Yi, SUN Jianjun

2022, 27(1):  33-38.  doi:10.12092/j.issn.1009-2501.2022.01.005

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AIM: To evaluate the predictive performance of Warfarin Dose Calculator (WDC) based on Bayesian method, Warfarin Dosing and International Warfarin Pharmacogenetics Consortium (IWPC) Warfarin Dose Calculator based on Multiple Linear Regression (MLR) in the absence of warfarin related genotypes, in order to provide help for patients using warfarin in areas where there is unconditional warfarin related genotypes detection. METHODS: The predicted performance of each tool was evaluated by calculating the mean prediction error (MPE), root mean square error (RMSE) and the percentage of patients whose prediction error was within ±20% of the actual maintenance dose. All statistical analyses were performed by SPSS statistics 26.0 software. RESULTS: The Posteriori of the WDC had the lowest MPE, RMSE and highest percentage of patients whose prediction errors within ±20% of the actual maintenance dose. In addition, the predictive accuracy of the Priori and Posteriori of WDC is significantly higher than that of Warfarin Dosing and IWPC warfarin dose calculator. CONCLUSION: Among the three assistant tools for warfarin dose prediction, Warfarin Dose Calculator based on Bayesian method may be more suitable for warfarin dose prediction of patients in unconditional warfarin related genotypes detection area.

Effects of extracorporeal membrane oxygenation on pharmacokinetics and pharmacodynamics of daptomycin in critically ill patients

HU Linlin, XU Silu, LI Weilan, HE Jie, ZHANG Jinglu, SHAO Hua

2022, 27(1):  39-46.  doi:10.12092/j.issn.1009-2501.2022.01.006

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AIM: To investigate the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/pharmacodynamics (PK/PD) of daptomycin in critically ill patients.  METHODS: Twenty four patients with severe infection in our hospital were randomly selected and divided into ECMO group and non ECMO group. They were intravenously injected with daptomycin 500 mg qd. After the drug reached the stability statement, venous blood was collected at different time points before and after the infusion. The plasma drug concentration was measured and the pharmacokinetic parameters were calculated. The probability target acquisition (PTA) and the cumulative fraction response (CFR) were calculated by Monte Carlo simulation. RESULTS: After dosing, the main pharmacokinetic parameters in ECMO and non-ECMO group were calculated and listed as follows: Cmax were (85.5±25.4) μg/mL and (79.4±29.2) μg/mL, AUC0-24 were (674.2±267.2) mg·L-1·h and (952.9±304.5) mg·L-1·h，t1/2 were (10.9±2.1) h and (11.6±4.3) h，Vd were (0.21±0.12) L/kg and (0.150±0.061) L/kg，CL were (13.3±4.7) mL·h-1·kg-1 and (9.2±3.4) mL·h-1·kg-1. There were significant differences in AUC0-24 and CL between the two groups, and there was no significant difference in other pharmacokinetic parameters. Monte Carlo simulation results showed that when the sensitivity of MRSA to daptomycin decreased (MIC≥1 mg/L), the PTA values of ECMO group, non-ECMO group and healthy volunteers were less than 90%. CONCLUSION: ECMO may affect the PK/PD of daptomycin in patients with severe infection to a certain extent. When MIC≥1 mg/L, it is recommended to increase the dosage to achieve the expected antibacterial effect. In view of the individual differences of daptomycin in patients with ECMO, therapeutic drug monitoring (TDM) should be implemented in these patients, and the administration scheme should be adjusted according to the sensitivity of MRSA pathogens to drugs.

Clinical efficacy and modeling evaluation of He-wei-zhi-xie capsules in treating diarrhea patients 

XU Liying, ZHANG Gaosong, HUANG Xiaomin, HUANG Jihan, WANG Shuhua

2022, 27(1):  47-55.  doi:10.12092/j.issn.1009-2501.2022.01.007

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AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie (HWZX) capsules in diarrhea patients.  METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter Emax. A total of 146 cases of adverse event and 13 cases of adverse reaction were observed in the experiment. Adverse event ratio was 6.39%, and adverse reaction ratio was 0.57%. There were 2 cases of serious adverse event with 0.09% of serious adverse event ratio and no serious adverse reaction case. CONCLUSION: HWZX capsules can effectively reduce the number of diarrhea, and has a low incidence of adverse reactions and high safety in this study, which is a therapeutic drug worthy of promotion.

Bioequivalence of amlodipine besylate tablets in Chinese healthy subjects

GAO Rong, MA Yazhong, ZHAO Haixia, WANG Zhaoyuan, ZHANG Weihong, YUAN Hailong

2022, 27(1):  56-62.  doi:10.12092/j.issn.1009-2501.2022.01.008

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AIM: To evaluate the bioequivalence of two kinds of amlodipine besylate tablets in Chinese healthy subjects under fasting and fed conditions. METHODS: Twenty-four healthy subjects were enrolled, and a random, open, single-dose, two preparations, two sequences and double-crossover design was used to give the test or reference preparations under fasting and postprandial conditions. The concentration of metformin in plasma was detected by LC-MS/MS, and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence. RESULTS: In fasting state, the mean of Cmax, AUC0-t, and AUC0-∞ of the test and reference preparations was (3 462.08±683.46) pg/mL, (159 891.00±45 951.00) pg·mL-1·h, (194 850.00±63 829.00) pg·mL-1·h, (3 346.09±710.09) pg/mL, (159 065.00±45 214.00) pg·mL-1·h, (190 461.00±66 160.00) pg·mL-1·h, respectively. The ratio of geometric mean and its 90% confidence interval are 104.82% (100.35%, 109.50%), 103.32% (98.13%, 108.78%), 103.98% (97.95%, 110.38%). In fed condition, the mean of Cmax, AUC0-t, and AUC0-∞ of the test and reference preparations was (2 785.00±600.91) pg/mL, (138 289.00±30 684.00) pg·mL-1·h, (158 765.00±39 260.00) pg·mL-1·h, (2 960.00±671.27) pg/mL, (140 990.00±33 326.00) pg·mL-1·h, (163 996.00±43 606.00) pg·mL-1·h, respectively. The ratio of geometric mean and its 90% confidence interval are 94.89% (88.94%, 101.23%), 97.96% (92.85%, 103.34%) and 97.26% (91.61%, 103.25%). CONCLUSION: Two kinds of amlodipine besylate tablets are bioequivalent, and have similar safety and tolerability in Chinese healthy subjects.

Application of artificial neural network model in bioequivalence study of candesartan cilexetil tablets

HU Yin, YANG Dandan, XU Yichao, SHAO Rong, RUAN Zourong, JIANG Bo, CHEN Jinliang, LOU Honggang

2022, 27(1):  63-69.  doi:10.12092/j.issn.1009-2501.2022.01.009

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AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs.  METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet (test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the Cmax, AUC0-t, and AUC0-∞ of the test product were all fall within 80.00%-125.00% of the reference product, indicating the two formulations were bioequivalent. The candesartan plasma concentration prediction model was constructed by MATLAB software. The performance verification result of MSE is 0.000 781, the gradient amplitude is 0.000 432, the number of verification checks is 0. Good correlation coefficients are showed in the training group, the verification group, and the prediction group (r>0.99). CONCLUSION: The test and the reference product of candesartan cilexetil are bioequivalent under fasting and fed conditions. The established prediction model can accurately predict the candesartan plasma concentration in humans after oral administration. It may provide a basis for clinical rational use of drugs.

Bioequivalence study of buthlphthalide injection in Chinese healthy volunteers

CAI Mingmin, SHAO Jing, TANG Lu, SUN Qiuyue, DOU Ting, QIAN Wei, WANG Huiping

2022, 27(1):  70-76.  doi:10.12092/j.issn.1009-2501.2022.01.010

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AIM: To establish a method to investigate pharmacokinetics and bioequivalence of buthlphthalide injection. METHODS: An open, randomized, and two-cycle crossover study was conducted in 24 healthy volunteers. Plasma concentrations of buthlphthalide were determined by LC-MS/MS after administering a single dose of reference drug or test drug. Main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. RESULTS: For the test drug and the reference drug, the main pharmacokinetic parameters of flurbiprofen were as follows: AUC0-t was (541.0±78.6) ng·mL-1·h and (525.0±76.1) ng·mL-1·h, AUC0-∞ was (571.0±82.1) ng·mL-1·h and (555.0±88.1) ng·mL-1·h, Cmax was (295.0±62.7) ng/mL and (291.0±56.5) ng/mL, and the median of Tmax was 0.92 (0.33, 0.92) h and 0.92 (0.33, 0.93) h, respectively. Under two kinds of conditions, 90%CIs of AUC0-t, AUC0-∞ and Cmax of the test preparation were 80%-125% of the corresponding parameters of the reference preparation，and there was no statistical significance in Tmax between the two preparations (P＞0.05)．CONCLUSION: The test drug and the reference drug are bioequivalent．

Literature analysis of the design and results of the First-In-Human clinical trials of drugs from 2009 to 2020

DENG Kunhong, LIU Yaxin, SUN Yuanyuan, CHEN Wenjing, YANG Nan, HU Zhanqing, CHEN Kaifeng, HUANG Jie, XIANG Yuxia, YANG Guoping

2022, 27(1):  77-85.  doi:10.12092/j.issn.1009-2501.2022.01.011

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AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials.  METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

Interpretation of pharmacokinetic-based criteria for supporting alternative dosing regimens of programmed cell death receptor-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) blocking antibodies for treatment of patients with cancer guidance for industry

LIU Wei, XUE Junsheng, YU Zhiheng, WANG Ziyu, CHEN Rong, ZHOU Tianyan

2022, 27(1):  86-94.  doi:10.12092/j.issn.1009-2501.2022.01.012

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In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.

Influencing factors of PD-1/PD-L1 immune checkpoint inhibitor immunotherapy for gastric cancer

LIU Le, QI Wenbo, BAI Yuping, LIU Qian, YIN Zhenyu, LI Xiaomei, YU Yang, CHEN Hao

2022, 27(1):  95-101.  doi:10.12092/j.issn.1009-2501.2022.01.013

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Gastric cancer has high morbidity and mortality, and limited treatment options for advanced cancer. In recent years, with the advent of targeted drugs (including VEGFR-2 antagonists, anti-HER-2 antibodies) and immunotherapeutics (such as anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies), the efficacy of advanced gastric cancer has been increased. Currently, the clinical data of PD-1 and its ligand PD-L1 inhibitors have achieved phased success, but which factors affect the efficacy of PD-1/PD-L1 immune checkpoint inhibitors immunotherapy, and how to select the benefited patient population and establish the prognosis evaluation system are the urgent problems to be solved. Therefore, this review elaborated the factors affecting the immunotherapy effects of PD-1/PD-L1 inhibitors from the aspects of systemic chemotherapy, intestinal microbiota, MSI, Hp infection, Epstein-Barr virus, TMB, and tumor infiltrating lymphocytes, in order to provide new ideas for clinical work.

Research progress on bile acid metabolism mediated by uridine diphosphate glucuronic acid transferase and its endogenous and exogenous influencing factors 

GUO Shengjie, GUAN Xirui, CAO Wenli, LIANG Sicheng, QI Xiaoyi, GE Guangbo, LV Muhan

2022, 27(1):  102-107.  doi:10.12092/j.issn.1009-2501.2022.01.014

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Uridine diphosphate glucuronic acid transferase (UDP-glucuronosyltransferases, UGT) is an important Ⅱmetabolic enzymes in the body. It is invovled in the metabolism of exogenous compounds, and also in endogenous substances such as bile acid metabolism and regulation. Parsing uridine diphosphate glucuronic acid transferase mediated bile acid metabolism and its influence factors can help enhance related disease treatment and prevention. Studies have shown that the interaction between UGT and bile acids is influenced by many endogenous and exogenous factors. This paper will focus on the effects of internal and exogenous factors such as nuclear receptors, genetic factors, xenobiotics and liver-related diseases on the action of UGT enzyme, and discuss the potential mechanism of bile acid balance intervention.

Research progress of PARP inhibitors in pancreatic cancer

ZHENG Ying, ZHANG Ling, YAO Li, WANG Qianhe, ZHU Kexiang

2022, 27(1):  108-115.  doi:10.12092/j.issn.1009-2501.2022.01.015

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Pancreatic cancer is a highly malignant tumor. PARP inhibitor (PARPI) is the first synthetic antineoplastic drug developed based on the concept of synthetic lethality and has been clinically approved for the treatment of ovarian cancer and breast cancer. Due to specific DNA repair defects, studies have found that tumors with BRCA1/2 germline mutations are sensitive to PARPI, but the specific mechanism of action is still unclear. A number of clinical trials for pancreatic cancer have been carried out. Phase III POLO studies have shown that Olaparib is effective and well tolerated as a maintenance treatment in patients with germline BRCA1/2 mutations and patients with metastatic pancreatic cancer after platinum-based induction chemotherapy. Clinical studies related to combination therapy suggest that the benefit of adding PARPI is likely to come from the maintenance phase of treatment. In general, PARPI has broad prospects in the treatment of pancreatic cancer.

Advances in the study of iodine-resistant differentiated thyroid cancer

CHEN Wenjie, WANG Yabing, CHEN Xiaolin, REN Junling, ZHAO Wanjun, CHEN bin

2022, 27(1):  116-120.  doi:10.12092/j.issn.1009-2501.2022.01.016

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Thyroid cancer is one of the most common malignant tumors. After standardized surgery, selective 131I radiotherapy and gonadotropin suppression therapy, the overall prognosis of most patients with differentiated thyroid cancer is good. However, there are still a small number of patients who are not sensitive to radioactive iodine treatment and have mutations of one or more oncogenes, which become iodine-resistant differentiated thyroid cancer. The application of traditional treatment methods cannot achieve satisfactory efficacy, the disease progresses rapidly and the mortality rate is high. This article reviews the progress in the diagnosis and treatment of iodine-resistant differentiated thyroid cancer in order to obtain the necessary time for early identification and targeted therapy.

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2022, 27(1):  117. 

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