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Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Table of Content

    Volume 28 Issue 11
    26 November 2023
    Tetramethylpyrazine protected against intestinal ischemia-reperfusion injury induced pyroptosis by inhibiting NLRP3 inflammasome activation
    CAO Xuefen, LENG Yufang, HAN Xiaoxia, HOU Xiaoyu, LYU Xingjiao, Janvier NIBARUTA
    2023, 28(11):  1201-1208.  doi:10.12092/j.issn.1009-2501.2023.11.001
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    AIM: To verify the role of tetramethylpyrazine (TMP) in intestinal ischemia-reperfusion (I/R) injury and its relationship with pyroptosis. METHODS: Thirty-six healthy SPF male C57BL/6 mice, 8-12 weeks old, weighing 20-25 g, were divided into six groups randomized by table of random number (n = 6/group): Sham group (S1 group)、Ischemia/reperfusion group (I/R1 group), I/R + TMP treatment group: 15 mg/kg (T15 group), 30 mg/kg (T30 group), 60 mg/kg (T60-1 group), 120 mg/kg (T120 group). In experiment 2, thirty healthy SPF male C57BL/6 mice were divided into five groups (n = 6/group): Sham group (S2 group), I/R group (I/R2 group), I/R + dimethyl sulphoxide (DMSO) group (DMSO group), I/R + TMP (60 mg/kg) group (T60-2 group), and I/R + DMSO + TMP (60 mg/kg) + Nigericin sodium salt (NSS) group (T60+NSS group). I/R-induced intestinal injury was established by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion, while the sham group mice underwent isolation of superior mesenteric artery without clamping. An NLRP3 agonist NSS was dissolved in DMSO, was intraperitoneally injected (4 mg/kg) 60 minutes before ischemia. And DMSO group mice were intraperitoneally administered with corresponding DMSO. Different TMP dosage groups and T60+NSS group mice were intraperitoneally administered with TMP 30 minutes before ischemia. IL-1β and IL-18 concentrations in the intestine were measured at 120 minutes after reperfusion by ELISA. The pathological changes of the sections were observed by optical microscope, and the intestinal mucosal injury was evaluated by Chiu's score grading. Western blot was used to detect NLRP3, Caspase-1, and GSDMD in intestinal tissue. RESULTS: Statistically significant increase of Chiu's score, IL-1β, IL-18 concentrations in the I/R1 group were found as compared with S1 group (P<0.05). And compared with I/R1 group, Chiu's score and IL-1β, IL-18 concentrations in the T60-1, T120 groups were reduced (P<0.05). Moreover, Chiu's score in the T120 group was lower than that in the T60 group (P<0.05). We found a statistically significant increase of Chiu's score and IL-1β, IL-18 concentrations and the expression of NLRP3, GSDMD, caspase-1 in the I/R group (P<0.05)as compared with S2 group. Compared with I/R2 group, Chiu's score, IL-1β, IL-18 concentrations and NLRP3, GSDMD, caspase-1 expression in the T60-2 group was reduced (P<0.05). Compared with T60-2 group, Chiu's score, IL-1β, IL-18 concentrations and NLRP3, GSDMD, caspase-1 expression in the T60+NSS group were upregulated (P<0.05). CONCLUSION: The protective effect of TMP against intestinal I/R injury was dose-dependent. And TMP can decrease pyroptosis mainly by inhibiting the activation of the NLRP3 inflammasome.
    Baicalein promotes laryngeal cancer cell death and inhibits invasion via miR-125b-5p/IRF4 axis
    WANG Jian, SUN Yongdong, ZHOU Xingwei, LIU Lei, CHEN Long, TONG Xingke, ZHU Jiali
    2023, 28(11):  1209-1218.  doi:10.12092/j.issn.1009-2501.2023.11.002
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    AIM: To investigate the mechanism of baicalin-induced apoptosis in human laryngeal cancer cells. METHODS: AMC-HN-8 cells were selected for the study, and baicalin was applied to the cells at different concentrations (0, 10, 30, 100, and 300 μmol/L), and the half-inhibitory concentration (IC50) was measured by the CCK-8 method. Bax, cleaved-caspase-3, Cyto-c, IRF4 protein expression by protein blotting (Western blot); miR-125b-5p and IRF4 expression by RT-qPCR. Dual-luciferase reporter gene validation of Targetscan prediction (binding of miR-125b-5p to IRF4-3'UTR); apoptosis and necrosis inhibitors explore the way baicalein induces death in laryngeal cancer cells. AMC-HN-8 was then divided into blank group, baicalein (IC50), miR-125b-5p inhibitor group, baicalein+inhibitor NC group, baicalein+miR-125b-5p inhibitor group, and cell invasion and clone formation assays to detect cell invasion and proliferation ability, respectively. Apoptosis was detected by flow cytometry. RESULTS: Baicalein inhibited the proliferation of AMC-HN-8 cells in a dose-dependent manner with an IC50 value of 47.31 μmol/L. Compared with the blank group, 47.31 μmol/L baicalin induced apoptosis and inhibited cell invasion, while upregulating the expression of miR-125b-5p and suppressing the mRNA and protein levels of IRF4. The luciferase results showed that the miR-125b-5p mimic was able to inhibit the activity of the IRF4-3'UTR promoter relative to the NC mimic (mimic) group. Baicalein induces laryngeal cancer cell death in an apoptotic manner. In addition, the combination of 47.31 μmol/L baicalin and miR-125b-5p inhibitor affected the behavior of AMC-HN-8 cells, showing that compared with the blank group, the baicalin group showed a decrease in the number of cell clones, weakened invasion ability, and increased apoptosis; the miR-125b-5p inhibitor group showed an increase in the number of cell clones, enhanced invasion ability and decreased apoptosis. The baicalin+inhibitor NC group was consistent with baicalin, with no significant effect of inhibitor NC on cell behavior. The cloning, invasion, and apoptosis of cells in the baicalin+miR-125b-5p inhibitor group were intermediate between the baicalin and miR-125b-5p inhibitor groups. CONCLUSION: Baicalin inhibits the proliferation of AMC-HN-8 cells, and the mechanism may be related to miR-125b-5p targeting to inhibit the expression of IRF4, inducing the pro-apoptotic proteins Bax, cleaved-caspase3, and Cyto-c, and inhibiting the apoptosis suppressor protein Bcl-2 thereby inducing apoptosis.
    Exploring the mechanism of elemene synergistic bortezomib against multiple myeloma by ROS-NF-κB-p38MAPK pathway
    ZHU Ruifang, GUO Dongkai, ZHI Hui, JIANG Yiguo, ZHANG Yueling, QIAN Xiaoping, JI Shiliang
    2023, 28(11):  1219-1226.  doi:10.12092/j.issn.1009-2501.2023.11.003
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    AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P<0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P<0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.
    Interaction effect and predictive efficacy of blood glucose and blood calcium on the prognosis of patients with acute severe pancreatitis
    HUANG Kaige, XU Qinhua, WANG Wei
    2023, 28(11):  1227-1234.  doi:10.12092/j.issn.1009-2501.2023.11.004
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    AIM: To investigate the interactive effects of blood glucose and blood calcium on the prognostic impact of patients with acute severe pancreatitis (SAP) and to analyze their predictive efficacy on prognosis. METHODS: One hundred and seven patients with SAP admitted to our hospital from September 2019 to October 2022 were selected for the study and were divided into poor and good groups according to their prognosis within 28 d. The blood glucose, blood calcium, modified Marshall score, bedside acute pancreatitis severity score  (BISAP) were compared between the two groups before treatment, after 3 d of treatment, and after 7 d of treatment, and the correlation between blood glucose, blood calcium and modified Marshall score and BISAP score was analyzed. The blood glucose levels of patients with different blood calcium were compared. Cox regression was used to analyze the factors associated with prognosis. The presence and type of interaction between blood glucose and blood calcium on prognosis were analyzed using the interaction coefficient γ and relative risk (RR) values. The subject operating characteristic curve (ROC) was used to analyze the predictive efficacy of blood glucose and blood calcium on prognosis. RESULTS: The blood glucose, modified Marshall score, and BISAP score of the adverse group after treatment were higher than those of the good group, while the blood calcium was lower than that of the good group (P<0.05). After 3 and 7 days of treatment, blood glucose was positively correlated with improved Marshall score and BISAP score (P<0.05). The blood glucose level in patients with decreased blood calcium was higher than that in patients with normal blood calcium (P<0.05). The decrease of blood calcium had positive interaction with the increase of blood glucose (P<0.05). After 3 and 7 days of treatment, the AUC of blood glucose combined with blood calcium was greater than that predicted by single index (P<0.05). CONCLUSION: Blood glucose and blood calcium are related to the severity of the disease in SAP patients. There is an interaction between blood glucose and blood calcium in predicting the prognosis of SAP patients. The combined detection of blood glucose and blood calcium has a certain predictive effect on the prognosis of SAP patients.
    Isonlosinine induces autophagy of PC9 cells by ERK signaling pathway in lung cancer
    LI Fei, DING Huiqin, CHEN Mengjing
    2023, 28(11):  1235-1240.  doi:10.12092/j.issn.1009-2501.2023.11.005
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    AIM: To investigate the effects of isonlosinine on proliferation, invasion, migration and autophagy of PC9 cells in non-small cell lung cancer (NSCLC), and to explore its possible molecular mechanism. METHODS: The effect of Isoliensinine on the proliferation of PC9 cells were measured by CCK-8 assay, and the IC50 value of PC9 cells was calculated. Wound healing and transwell experiments were used to study the effect of Isoliensinine on migration and invasion of PC9 cells in vitro, respectively. The formation of autophagosome was observed with acridine orange staining under fluorescence microscope. The expression levels of LC3, p-ERK and ERK in the PC9 cells were determined by western blot. RESULTS: Isonlosinine significantly inhibited the proliferation of PC9 cells. IC50 of isonlosinine (24 h) for the PC9 cells was 34.11 μmol/L. Isonlosinine significantly inhibited cell migration and invasion of PC9 cells. The results of acridine orange fluorescent staining showed that the number of the intracellular acid dye follicular bright red fluorescence in PC9 cells was significantly increased after isonlosinine treatment, while the autophagic lysosomes were rarely observed in control group. The expression of LC3-II in PC9 cells was significantly enhanced after isonlosinine treatment. Furthermore, molecular mechanism study showed that isonlosinine could activate the expression level of p-ERK. CONCLUSION: Isoliensinine significantly inhibits the proliferation, migration and invasion, and induces autophagy of PC9 cells, which may be correlated with the activation of ERK signaling pathway.
    Mechanism of DCLK1 transcriptional regulation in HCC
    WU Xianchuang, LIU Yuxin, NIU Yuji, HE Jinjin, QIAO Hui, ZHANG Leilei
    2023, 28(11):  1241-1246.  doi:10.12092/j.issn.1009-2501.2023.11.006
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    AIM: To investigate the molecular mechanism through which DKK1 is transcriptionally regulated in HCC (hepatocellular carcinoma) cells. METHODS: Real time PCR was used to explore whether EGFR was involved in regulating DCLK1 mRNA expression in HCC cells; Western blot assay was used to examine whether EGFR-mediated the up-regulation of DCLK1 protein in HCC cells; Immunohistochemical (IHC) analyses were used to examine the protein expression of EGFR and DCLK1 in 39 human HCC tumor specimens. RESULTS: EGF promoted the expression of DCLK1 mRNA and protein in HepG2 and Huh-7 cells (P<0.05, P<0.01), while knockdown of EGFR with two specific siRNA could reverse EGF-induced the up-regulation of DCLK1 mRNA and protein (P<0.01). IHC analyses revealed that the amount of EGFR correlated significantly with that of DCLK1 (r=0.669 6). CONCLUSION: EGFR promoted DCLK1 transcription in HCC.
    Curative effect of fuzheng xiaoliu granules in the treatment of primary liver cancer and analysis of serum metabolomics
    SHI Dandan, SUN Yiyao, CHEN Xiaoqi, YANG Fangming, ZHANG Chuanlei, WANG Xinting, YUAN Changwei, CHEN Xinju
    2023, 28(11):  1247-1262.  doi:10.12092/j.issn.1009-2501.2023.11.007
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    AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P<0.05). There was no statistical significance in the comparison of alpha-fetoprotein and child-pugh grade between the two groups after treatment (P>0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.
    Clinical characteristics of anticoagulant rodenticide poisoning in northern Anhui analysis of the effect of the vitamin K1 medication regimen on the efficacy
    TAO Yanyan, TANG Yajie, WANG Lili, WANG Fangli, LU Guoyu, FAN Fangtian
    2023, 28(11):  1263-1268.  doi:10.12092/j.issn.1009-2501.2023.11.008
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    AIM: To analyze the clinical characteristics of anticoagulant rat poisoning and vitamin K1 to improve clinical diagnosis and treatment. METHODS:  The clinical data of 51 patients hospitalized in the emergency department of our hospital from January 2020 to December 2022, including poisoning mode, poisoning time (poison exposure to admission time), clinical manifestations, coagulation function, vitamin K1 dosage and treatment results, etc. All patients were followed up for 3 months. RESULTS: Among the 51 patients, 27(52.94%) were toxic, the highest proportion. PT, APTT, and INR improved significantly at discharge compared to admission (P<0.01). Twenty three patients had bleeding symptoms during admission, PSS score: 12 mild, 7 moderate and 4 severe; Forty six patients with clear history of toxic exposure were divided into 48 h and <48 h groups according to the poisoning time. By comparison between the two groups, the difference was significant (P<0.01). Twenty eight patients had abnormal coagulation function on admission, which was divided into 12 and 16 in 40 mg/d and > 40 mg/d and a long time in 40 mg/d group, but not statistically significant (P>0.05). CONCLUSION: The symptoms of anticoagulant rat dose poisoning are coagulation dysfunction and bleeding; the prolonged coagulation abnormality is more significant; the larger dose of vitamin K1 is not significantly different than the normal dose, and the timeliness and maintenance time of vitamin K1 treatment are more important. 
    Effect of prophylactic anticoagulation duration on venous thrombosis after total hip/knee arthroplasty
    LU Kepeng, LIU Caihong, BI Ying
    2023, 28(11):  1269-1274.  doi:10.12092/j.issn.1009-2501.2023.11.009
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    AIM: By assessing the impact of prolonged prophylactic anticoagulation on venous thromboembolism in patients undergoing total hip/knee arthroplasty, we dared to hope to further clarify whetherprolonged prophylactic anticoagulation duration can benefit patients undergoing total hip/knee arthroplasty. METHODS: The incidence of venous thromboembolism and bleeding events within 90 days of total hip/knee arthroplasty in patients who underwent total hip/knee arthroplasty in the department of orthopaedic surgery was retrospectively analyzed from January 2019 to April 2022. The Kaplan-Meier method survival curve was used to determine whether there is a relationship between the duration of prophylactic anticoagulation and the incidence of postoperative bleeding. RESULTS: A total of 115 patients undergoing primary total hip/knee surgery from January 2019 to April 2022, were enrolled in this study. Among them, there were 38 cases in the short-term prophylactic anticoagulation group and 77 cases in the extended prophylactic anticoagulation group. There were 23 cases (20%) of venous thromboembolism within 90 days after surgery, of which 12 cases (31.58%) were in the short-term anticoagulation group and 11 cases (14.29%) were in the extended anticoagulation group, and there was a statistical difference in the incidence of venous thromboembolism within 90 days after surgery between the two groups in terms of the duration of anticoagulation prevention. CONCLUSION: The results show a significant correlation between the duration of prophylactic anticoagulation and the incidence of venous thromboembolism within 90 days after total hip/knee arthroplasty, which suggests that prophylactic anticoagulation for 15-35 days after undergoing total hip arthroplasty or total knee arthroplasty reduces the incidence of postoperative VTE, and there is no significant difference in bleeding risk depending on the duration of anticoagulant prophylaxis.
    Application of population modeling analysis to evaluate the impact of gene polymorphism on drug PK/PD 
    LIU Lu, SHI Yufei, HE Qingfeng, XU Fengyan, WANG Kun, CAI Weimin, XIANG Xiaoqiang
    2023, 28(11):  1275-1282.  doi:10.12092/j.issn.1009-2501.2023.11.010
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    Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD.
    Research progress on the role of the Nrf2 signaling pathway in the complications associated with obstructive sleep apnea
    ZHU Haobin, YUE Hongmei, WU Xingdong, LIU Miaomiao, LI Yating, XU Jinhui
    2023, 28(11):  1283-1291.  doi:10.12092/j.issn.1009-2501.2023.11.011
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    Mammalian cell defense mechanisms are constantly evolving in response to increasing endogenous and exogenous oxidative stress factors. In recent years, as research has deepened, nuclear factor E2-related factor 2 (Nrf2) has been hailed as a "star" molecule in antioxidant damage defense. Billions of dollars have been spent internationally on developing targeted activators or inhibitors. Obstructive sleep apnea (OSA) is the most common form of sleep breathing disorder in clinical practice. Oxidative stress is one of its main pathological mechanisms and is closely related to target organ damage in the heart, brain, lungs, kidneys, and other systems. Recent research has revealed the mechanistic relationship of the Nrf2 pathway in OSA complications, and some natural Nrf2 activators have demonstrated emerging therapeutic effects in animal experiments. However, the activation mode and effect pathway of Nrf2 in different target organs of OSA have not been clarified. Therefore, this article reviews the research progress of the Nrf2 pathway in OSA and its complications, to deepen understanding of the mechanism of OSA complications and provide a potential treatment strategy.
    Regulation mechanism of post-translational modification of farnesoid X receptor
    LIU Zhaofeng, LI Ling, NA Shufang, YUE Jiang, YE Qifa
    2023, 28(11):  1292-1298.  doi:10.12092/j.issn.1009-2501.2023.11.012
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    Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation,sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases.This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.
    Research progress on the relationship between pediatric epilepsy and vitamin D
    LI Chenhao, YU Xihua, YAN Wenhao, CHAI Yuxia, LI Yanyan, LI Kun, LI Zeyun
    2023, 28(11):  1299-1306.  doi:10.12092/j.issn.1009-2501.2023.11.013
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    Epilepsy is a long-term, chronic, recurrent, multi-factorial, multi-symptomatic nervous system disease, and was caused by abnormal discharge of brain neurons. Etiology can cause irreversible brain dysfunction and even death. There are about 6.5 million children with epilepsy in China, with incidence rate twice that of adult, presenting serious threaten to children's growth and development. Vitamin D has been well-known for crucial importance to development of nervous, skeletal, and immune system. Studies have found that pediatric epilepsy as well as other neurological diseases were closely related with vitamin D deficiency. First, a large number of studies have shown that vitamin D in children with epilepsy is affected by epilepsy itself; second, the use of anti-seizure medicines can alter metabolism of vitamin D by inducing cytochrome oxidases; third, the inducement was concerned to varieties, combination and duration of anti-seizure medicines; fourth, it was expected that supplement of vitamin D during antiepileptic treatment would guarantee an improvement of treating given that anti-seizure medicines may lead to deficiency of vitamin D. Large numbers of researches have reported on the correlation ship between pediatric epilepsy and vitamin D. However, there is still a lack of systematic review. This article aims to retrospect the research progress of relationship between pediatric epilepsy and vitamin D, and provide valuable feedbacks on further treatment of pediatric epilepsy.
    Interactions and clinical significance of gut microbiota and levothyroxine
    ZHOU Jiating, ZHANG Xuan, XIE Zilan, LI Zhi
    2023, 28(11):  1307-1314.  doi:10.12092/j.issn.1009-2501.2023.11.014
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    Levothyroxine is a class of thyroid hormone medication mainly used in the clinical treatment of thyroid hormone replacement therapy and thyrotropin suppression therapy. In recent years, studies have found a close correlation between the human gut microbiota and the occurrence and development of thyroid diseases, as well as changes in thyroid hormone levels. Therefore, understanding the impact of levothyroxine on the gut microbiota, as well as the effects of the gut microbiota on the metabolism and absorption of levothyroxine, is of great significance for the treatment of thyroid diseases and the rational use of clinical medication. This article explores the interaction between the gut microbiota and levothyroxine and summarizes the current clinical findings of the gut microbiota in levothyroxine therapy.
    Pathogenic mechanism and research progress of adipocytokines in endometrial cancer
    MA Yitong, MA Jianhong, GAO Yating, LIU Chang
    2023, 28(11):  1315-1320.  doi:10.12092/j.issn.1009-2501.2023.11.015
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    Endometrial carcinoma (EC) is one of the most common gynecologic tumors, and its incidence and mortality are increasing.The prognosis is usually favorable when the disease is diagnosed at an early stage. However, the prognosis for patients with recurrence and metastasis is relatively poor. As one of the risk factors for EC, the complex and widespread oncogenic role of obesity in EC has been validated, then the oncogenic and pro-carcinogenic mechanisms of adipocytokines secreted by adipose tissue in EC have attracted continuous attention. This review highly summarizes and concludes the previous relevant literature on the role of adipocytokines in endometrial cancer and the progress of research, and elucidates the correlation between adipocytokines and the occurrence risk, stage grading, and long-term prognosis of EC, as well as their signaling pathways and mechanisms of action in the development of EC. All this information will likely contribute to the development of novel molecular markers in EC, the discovery of new therapeutic targets, and the study of related targeted drugs, which may in turn break the current dilemma of early screening, early diagnosis, and treatment of recurrent and metastatic patients in EC in the future, resulting in an improvement of the long-term prognosis of patients with EC.
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    2023, 28(11):  1316. 
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