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

Table of Content

    Volume 26 Issue 2
    26 February 2021
    Salvianolic acid A improves palmitie acid-induced lipotoxicity in cardiomyocyte via inhibiting TLR4/JNK MAPK
    XU Tiantian, WU Xiangyao, PI Aiwen, CHAI Hui, ZHANG Bin, WANG Bangcai, DOU Xiaobing, ZHU Linwensi
    2021, 26(2):  121-128.  doi:10.12092/j.issn.1009-2501.2021.02.001
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    AIM: To reveal the ameliorative effect of salvianolic acid A on palmitie acid-induced lipotoxicity in H9C2 cells and to explore its potential molecular mechanisms preliminarily.  METHODS: H9C2 cell were induced by palmitie acid to establish a lipotoxicity model, while salvianolic acid A was added prior to palmitie acid treatment. Lactate dehydrogenase (LDH) was employed to detect cell damage. Cell counting Kit-8 was used to detect cell viability. The changes of mitochondrial membrane potential in cardiomyocyte were observed by rhodamine 123 staining. The molecular mechanisms of the ameliorative effect of salvianolic acid A was analyzed by Western Blotting. RESULTS: Palmitie acid at a concentration of 400 μmol/L significantly caused lipotoxicity damage to H9C2 cells (P<0.05). There was no cytotoxic effect of different concentrations of salvianolic acid A (10, 20, 40, 80 μmol/L) treatment on H9C2 cells (P>0.05). Salvianolic acid A intervention significantly improved lipotoxicity-induced cell death and reduction of cell mitochondrial membrane potential (P<0.05). The activation of toll-like receptor 4 (TLR4) significantly enhanced lipotoxicity-induced cell damage (P<0.05), while inhibition of TLR4 significantly reduced palmitie acid-induced lipotoxicity (P<0.05). In addition, salvianolic acid A effectively inhibited the upregulation of TLR4 and the downstream c-Jun N-terminal kinase (JNK MAPK) of TLR4 by palmitie acid treatment (P<0.05). CONCLUSION: Salvianolic acid A effectively improves lipotoxicity-induced cardiomyocyte damage. The inhibition of p38 signaling pathway is potentially involved in its protective effect. The protective effect may be related to the inhibition of TLR4/JNK MAPK signaling pathway, providing a potential molecular target for the prevention and treatment of lipotoxic cardiomyopathy.
    Gardenoside alleviates diabetic cardiomyopathy via inhibiting VPO1/ERK1/2 signaling pathway to improve myocardial apoptosis in rats
    ZHANG Weiping, JIANG Jianjun, CHEN Xiaofeng, XU Shasha
    2021, 26(2):  129-136.  doi:10.12092/j.issn.1009-2501.2021.02.002
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    AIM: To investigate the effect of geniposide (GE) on diabetic cardiomyopathy and its mechanism.  METHODS: Twenty-four adult male SD rats were randomly divided into three groups: Control group (n=8), DCM group (n=8) and DCM+ GE group (n=8). The diabetic cardiomyopathy model was established by high fat diet combined with streptozotocin (STZ), and H9C2 injury model was induced by hypochlorite (HOCl). After 12 weeks of intervention, the histopathological changes of heart were observed by HE and Masson staining, the level of cardiomyocyte apoptosis was detected by TUNEL staining, and the expression levels of VPO1/ERK1/2 signal pathway and apoptosis-related proteins were detected by immunohistochemistry and Western blot. The changes of ERK1/2, p-ERK1/2, Bcl-2 and Bax protein expression in cardiomyocytes were detected by Western blot after HOCl stimulation. After administration of ERK1/2 inhibitor U0126, the protein expression levels of ERK1/2, p-ERK1/2, Bcl-2 and Bax were detected again by Western blot assay. RESULTS: Compared with the control group, the arrangement of myocardial fibers was disordered and the content of myocardial collagen was significantly increased in DCM group by HE and Masson staining, while the myocardial injury was significantly improved in DCM+GE group (P<0.05). Compared with the control group, the apoptotic rates of cardiomyocytes and the ratio of Bax/Bcl-2 in DCM group were remarkably increased, while the myocardial apoptosis in DCM+GE group was significantly improved (P<0.05). The results of immunohistochemistry and Western blot showed that the expression of VPO1 and p-ERK1/2 was increased in DCM group, while the expression level of VPO1 and p-ERK1/2 was inhibited in DCM+GE group (P<0.05). When H9C2 cells were stimulated with HOCl, the expression of p-ERK1/2 and the ratio of Bax/Bcl-2 were both increased as compared with the control group, while the expression level of p-ERK1/2 and the ratio of Bax/Bcl-2 were decreased after the addition of ERK1/2 inhibitor U0126 (P<0.05). CONCLUSION: Geniposide alleviates the diabete-induced myocardial injury by suppressing cardiomyocyte apoptosis via inhibiting VPO1/ERK1/2 signal pathway.
    Ferulic acid protects palmitic acid-induced lipotoxicity in hepatocytes via inhibiting p38 MAPK
    FU Ai, XU Tiantian, YANG Zhen, HAN Qiang, DOU Xiaobing, LI Songtao
    2021, 26(2):  137-143.  doi:10.12092/j.issn.1009-2501.2021.02.003
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    AIM: To investigate the protective effect of ferulic acid on palmitic acid-induced lipotoxicity in HepG2 cells and to explore its potential molecular mechanisms.  METHODS: HepG2 cells were induced by palmitic acid to establish a lipotoxicity model, while ferulic acid was added prior to palmitic acid treatment. Lactate dehydrogenase (LDH) was used to detect cell damage. Methyl azozole trace enzyme reaction is used for 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) was employed to detect cell viability. The molecular mechanisms of the protective effect of ferulic acid was analyzed by Western Blotting. RESULTS: There was no cytotoxic effect of different concentrations of ferulic acid (25, 50, 100, 200 μmol/L) treatment on HepG2 cells (P>0.05). Ferulic acid intervention significantly inhibited palmitic acid-induced cell death and improved palmitic acid-induced reduction of cell mitochondrial membrane potential (P<0.05). The activation of p38 significantly enhanced palmitic acid-induced hepatocellular lipotoxicity (P<0.05), while inhibition of p38 significantly improved palmitic acid-induced cell damage (P<0.05). In addition, ferulic acid significantly inhibited the upregulation of p38 phosphorylation by palmitic acid treatment (P<0.05). p38 activator exposure blocked the protective effect of ferulic acid on lipotoxicity (P<0.05). CONCLUSION: Ferulic acid effectively improves hepatocellular injury induced by lipotoxicity.The inhibition of p38 signaling pathway is potentially involved in its protective effect. Ferulic acid may be an effective factor in the prevention and treatment of liver disease with lipotoxicity as a major pathological characteristic.
    Rosuvastatin regulates cerebral I/R damage to neurons by UCP2-SIRT3 signal
    YUN Qiang, DONG Xuejia, WANG Mengjiao, LIU Yahong, WANG Zhiguang, JIANG Mingfang
    2021, 26(2):  144-153.  doi:10.12092/j.issn.1009-2501.2021.02.004
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    AIM: To study the protective effect and mechanism of rosuvastatin on cerebral ischemia-reperfusion injury.  METHODS: (1) Cerebral infarction and OGD/R cell models were established to detect the effects of different concentrations of rosuvastatin on cell proliferation and apoptosis; (2) Different concentrations of rosuvastatin were used to treat OGD/R cell models and to observe rosuvastatin effects on cell morphology and expression and localization of UCP2-SIRT3 in cells; (3) UCP2 silent cell line was constructed to observe cell mitochondrial morphology and expression and localization of TOMM20 and SIRT3 molecules in cells, and to study the channels and mechanisms that play a protective role of rosuvastatin in OGD/R cell model; (4) The mitochondrial membrane potential, mitochondrial gene PGC1, Drp1 and Opa1 expression were detected to study the protective effect of rosuvastatin on mitochondria. RESULTS: (1) Rosuvastatin of different concentrations could significantly reduce OGD/R cell apoptosis and increase cell survival rate; (2) Rosuvastatin exerted cell protection by affecting the expression of UCP2 and SIRT3 in cells, thereby protecting cells from OGD/R injury; (3) Rosuvastatin affected the expression of TOMM20 by regulating UCP2, increased mitochondrial transmembrane transport and energy metabolism, enhanced mitochondrial function, and improved cell state and reduced apoptosis. CONCLUSION: Rosuvastatin inhibits mitochondrial damage of OGD/R cells by regulating UCP2/SIRT pathway, thereby exerting neuron protection.
    Correlation between changes of intestinal flora in children with Kawasaki disease and the levels of specific transcription factors RORγt, FOXP3 and T lymphocyte subsets
    XUAN Miaoyan, XU Zhen
    2021, 26(2):  154-160.  doi:10.12092/j.issn.1009-2501.2021.02.005
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    AIM: To explore the relationship between the changes of intestinal flora in children with Kawasaki disease (KD) and the specific transcription factor Rar related orphan receptor γt (RORγt), Fork head box P3 (FOXP3), and T lymphocyte subsets.  METHODS: A total of 110 children with KD in our hospital from January 2018 to June 2020 were selected and divided into simple KD group (68 cases) and KD co-infection group (42 cases) according to whether they were co-infected, and 42 healthy children during the same period were selected as the control group. The changes of the three groups of intestinal flora, RORγt, FOXP3, and T lymphocyte subsets were compared, and the relationship between the intestinal flora, RORγt, FOXP3, T lymphocyte subsets and KD co-infection was analyzed. Pearson correlation was used to analyze the correlation between the intestinal flora and RORγt, FOXP3, and T lymphocyte subsets.The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the predictive value of intestinal flora, RORγt, FOXP3, and T lymphocyte subsets for KD co-infection. RESULTS: Lactobacillus, Veillonococcus, Clostridium, FOXP3, CD3+, CD4+/CD8+ in the KD co-infection group were lower than those in the simple KD group and the control group, the simple KD group was lower than the control group. The Bacteroides, Enterococcus, Parabacter, and RORγt were higher than the simple KD group and the control group, and the simple KD group was higher than the control group (P<0.05). Logistic regression analysis showed that Lactobacillus, Veillonococcus, Clostridium, RORγt, FOXP3, CD3+, CD4+/CD8+ were important protective factors for KD and KD co-infection, Bacteroides, Enterococcus, and Parabacter were important risk factors for KD and KD co-infection (P<0.05). Pearson correlation analysis showed that Lactobacillus, Veillonococcus and Clostridium were negatively correlated with RORγt, and positively correlated with FOXP3, CD3+, CD4+/CD8+. Bacteroides, Enterococcus, and Parabacterium were positively correlated with RORγt, and negatively correlated with FOXP3, CD3+, CD4+/CD8+ (P<0.05). The ROC curve showed that the AUC of KD co-infection predicted by the combination of intestinal flora, RORγt, FOXP3, and T lymphocyte subsets was 0.888. The 95% CI was 0.822-0.953, P<0.001, the prediction sensitivity was 76.19%, and the specificity was 89.71%, which was better than the single prediction of each index. CONCLUSION: The changes of intestinal flora in children with KD are significantly related to RORγt, FOXP3, and T lymphocyte subsets, and are closely related to KD and KD co-infections. Combined detection can be an important means to predict infection.
    Tetrahydroxy stilbene glycoside protects mice from acetaminophen-induced liver injury: study based on metabonomics
    GAO Yan, LI Juntong, WU Qinglin, LI Lin, ZHANG Lan
    2021, 26(2):  161-166.  doi:10.12092/j.issn.1009-2501.2021.02.006
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    AIM: To explore the pharmaceutical effects of tetrahydroxy stilbene glycoside (TSG) on acute liver injury induced by acetaminophen (APAP) using method of non-targeted metabonomics.  METHODS: SPF C57BL/6 mice were randomly divided into the group of APAP-induced model and the group of TSG intervention groups (n=15). After intragastric administration of TSG for 7 days, the mice were injected once by APAP via intraperitoneal injection and the livers were taken 6 hours later. RESULTS: H&E staining, MDA and SOD tests showed that the injection of APAP could cause hepatic injury, but TSG could reduce the severity of liver injury. The results of metabolite detection showed that there were significant changes in ABC transporter, choline metabolism, central carbon metabolism, galactose and alanine amino acid metabolism in TSG groups compared with APAP model group. CONCLUSION: TSG protects against acute liver injury induced by APAP, mainly by improving lipid peroxidation and disorder of energy metabolism.
    Resveratrol suppresses NLRP3 inflammasome activation in colonic epithelial cells triggered by Escherichia coli O104∶H4
    DENG Li, TIAN Jing
    2021, 26(2):  167-173.  doi:10.12092/j.issn.1009-2501.2021.02.007
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    AIM: To study the effects of resveratrol (RES) on the mitochondrial damage, oxidative stress injury and NLRP3 inflammasome activation in colonic epithelial cells (Caco-2) induced by Escherichia coli O104∶H4.  METHODS: Caco-2 cells pre-treated with 200 μmol/L RES for 12 h, then cells were infected with 107 CFU/mL Escherichia coli O104∶H4 (MOI 10∶1) for 4 h. CCK-8 was used to detect the cell viability. qRT-PCR was performed to measure the expression levels of PGC1α, COX-4, NRF1, TFAM, SOD1 and HO-1 mRNA. Western blot was used to determine the expressions of NLRP3, CASP1 p20, CASP1 p10, pro-IL-1β and IL-1β. In addition, the mitochondrial membrane potential, oxygen consumption and ROS level were detected. RESULTS: Escherichia coli O104∶H4 infection could induce the expression levels of NLRP3, CASP1 p20, CASP1 p10, IL-1β protein and PGC1α, COX-4, NRF1 mRNA, and promote the oxygen consumption and ROS level, whereas significantly inhibit the cell viability, TFAM mRNA expression and the mitochondrial membrane potential (P<0.05). Furthermore, the expression levels of NLRP3, CASP1 p20, CASP1 p10, IL-1β protein and PGC1α, COX-4, NRF1 mRNA, and the oxygen consumption and ROS level were greatly decreased after treatment with RES in Caco-2 cells infected with Escherichia coli O104∶H4, whereas significantly induce the cell viability, TFAM mRNA expression and the mitochondrial membrane potential (P<0.05). In addition, ROS inhibitor (NAC) also could suppress the expressions of NLRP3 inflammasome and IL-1β. CONCLUSION: Escherichia coli O104∶H4 infection induces mitochondrial ROS release and NLRP3 inflammasome activation in Caco-2 cells, while RES exerts a preventive role in cells upon Escherichia coli O104∶H4 infection partially due to prevention of ROS production and activation of NLRP3 inflammasome.
    Model based efficacy evaluation of belimumab in patients with systemic lupus erythematosus
    ZHANG Lingxiao, LI Ting, XU Ling, LI Lujin, ZHENG Qingshan
    2021, 26(2):  174-181.  doi:10.12092/j.issn.1009-2501.2021.02.008
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    AIM: Belimumab is a fully humanized IgGl-X monoclonal antibody, which can specifically bind to soluble B cell stimulating factor (BLyS) preventing BLyS from binding to B cells to promote B cell apoptosis. It is the first drug approved by the FDA for the treatment of systemic lupus erythematosus (SLE). Based on data from global clinical literature of the drug, this study evaluated the effect of belimumab in the treatment of SLE through modeling analysis, quantitatively expressed its pharmacodynamic characteristics, and explored its potential influencing factors to establish the efficacy of belimumab in the treatment of SLE, which could provide a reference for the development of drugs for the treatment of SLE.  METHODS: Literature retrieval was conducted in Pubmed database. The clinical studies of belimumab in the treatment of SLE were included. Data, including the demography and baseline characteristics, dosage, administration methods, efficacy and safety of belimumab, was extracted to establish an analysis sets. Then a pharmacodynamic model was developed to evaluate the pharmacodynamic characteristics of the drug. The robustness of the model was evaluated via a variety of model evaluation methods. RESULTS: A total of 5 articles containing efficacy data were included in this analysis, involving 11 dosage groups (3 493 subjects). The results of covariate screening showed that race (Asian population or non-Asian population), age, course of disease, positive anti-dsDNA had no significant effect on the therapeutic effect of belimumab in SLE and there were no factors that had significant influence on model parameters. Model evaluation showed that the model established in this study can better describe the dose-effect relationship of belimumab in the treatment of SLE. The final model indicated that the response rate of the efficacy index SRI was close to the peak (approximately 99% of the peak level) at the 52nd week. The SRI response rates of placebo, belimumab 1 mg/kg intravenous injection, 10 mg/kg intravenous injection, and 200 mg subcutaneous injection were 46.1%, 52.9%, 57.9%, and 60.9%, respectively. After deducting the placebo effect, the SRI response rates (drug pure effect) of belimumab 1 mg/kg intravenously, 10 mg/kg intravenously, and 200 mg subcutaneously at 52 weeks were 6.8%, 11.8%, and 14.8%, respectively. CONCLUSION: The efficacy (SRI response rate) of belimumab in the treatment of SLE patients was close to its peak in the 52nd week. The SRI response rates of belimumab 1 mg/kg intravenously, 10 mg/kg intravenously, and 200 mg subcutaneously in the 52nd week were 52.9%, 57.9%, and 60.9%, respectively.
    Information construction of drug clinical trials based on literature analysis
    ZHANG Qian, HU Wei, YU Bin, QIN Huiling, CHEN Mingzhuang, LU Chao
    2021, 26(2):  182-189.  doi:10.12092/j.issn.1009-2501.2021.02.009
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    AIM: To sort out the research context of information construction of drug clinical trials and understand the hot spots and development trend of informatization construction of drug clinical trials.  METHODS: The knowledge map CiteSpace Ⅴ software was applied to analyze the 391 items of literature collected from China CNKI database during the year of 2000 to 2020. A thorough investigation was conducted from the perspectives of quantitative analysis, research institutes, author, research hot topics and the research trend. A knowledge map was generated to sort out the main ideas of the research of the drug clinical trial information construction. RESULTS: The results showed that in the past 20 years, the number of published papers related to the construction of clinical information of drugs fluctuated, and most of the major research institutions had strong research ability in this field. But the interactions within research institutions remained improved, and the academic exchanges between scholars still needed to be strengthened. The shift in hot-spot research reflected a greater focus on systematizing and protecting subjects' rights. CONCLUSION: The research of information construction of drug clinical trial mainly focuses on clinical trial, drug clinical trial, quality control and other aspects. It is the trend of future research to further improve the efficacy of trial management through information construction, ensure the reliability and standard of drug clinical trials, and effectively reduce the risks and hidden dangers of drug clinical trials.
    Bioequivalence study of pramipexole hydrochloride tablets in Chinese healthy subjects 
    WANG Xiaoru, ZHANG Xueyuan, WANG Xiaoyan, YANG Hanyu
    2021, 26(2):  190-195.  doi:10.12092/j.issn.1009-2501.2021.02.010
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    AIM: To assess the bioequivalence of pramipexole hydrochloride tablets with reference(Sifrol).  METHODS: A randomized, open-label, 2-period crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 volunteers for each condition). In each session, the subjects received a single oral dose of 0.25 mg test (T) or reference (R) formulation. Pramipexole concentrations in plasma were determined by a validated HPLC-MS/MS. Pharmacokinetic parameters were calculated using a non-compartmental model through Phoenix WinNonlin version 6.4. Other statistic analysis were analyzed by using software of SAS 9.3. RESULTS: The pharmacokinetic parameters of test drug and reference drug under fasted condition(n=20) were: Cmax (481.15±102.21) and (497.25±133.31)  pg/mL, Tmax 1.77 (0.5, 5) and 1.50 (0.5, 5) h, AUC0-t (6.18±1.49) and (6.20±1.28) pg·mL-1·h, AUC0-∞ (6.41±1.55) and (6.42±1.31) pg·mL-1·h, T1/2 (9.18±1.29) and (9.02±1.14) h, respectively. The 90%CIs of T/R for Cmax, AUC0-t and AUC0-∞ were 92.20%-103.10%, 94.06%-104.35%, 94.17%-104.07%, all were within the range of 80.00%-125.00%; the two formulations tested were considered bioequivalent when administered under fasted condition to healthy adult subjects. The pharmacokinetic parameters of test drug and reference drug under fedcondition (n=22) were: Cmax (515.36±83.28) and (500.05±64.12) pg/mL, Tmax 2.00 (1.00, 4.00) and 1.75 (1.00, 4.00) h, AUC0-t (5.94±1.36) and (5.67±1.05) pg·mL-1·h, AUC0-∞ (6.16±1.43) and (5.88±1.11) pg·mL-1·h, T1/2 (8.92±2.00) and (8.85±1.98) h, respectively. The 90%CIs of T/R for Cmax, AUC0-t and AUC0-∞ were 97.84%-107.41%, 99.03%-108.79%, 99.12%-108.68%, all were within the range of 80.00%-125.00%. All results meet the cretiria of bioequivance. CONCLUSION: This study suggests that the test formulation of pramipexole hydrochloride tablets are bioequivalent with the reference formulation of Sifrol in Chinese healthy subjects. 
    Treatment strategies of FGFR molecular alterations in lung squamous cell carcinoma
    XIE Rongrong, CHEN Zhi, YANG Yu, XIE Raoying, LI Pingping, SUN Shuangshuang, CHEN Wenjun
    2021, 26(2):  196-203.  doi:10.12092/j.issn.1009-2501.2021.02.011
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    Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death. Molecular targeted therapy for lung cancer, especially non-squamous non-small cell lung cancer, has developed rapidly and achieved good results. Several studies have found that fibroblast growth factor receptor (FGFR) signaling supports cancer cell proliferation and stimulates angiogenesis through different mechanisms, which plays a role in the development and progression of several tumors. This indicates that the inhibitions of FGFR signaling pathway may inhibit the proliferation of cancer cells. Dysregulation of FGFR signaling has been observed in some types of malignancy, including lung squamous cell carcinoma (LUSC), making FGFR a potential therapeutic target for LUSC. This review focuses on the role of FGFR signaling and some FGFR inhibitors in LUSC.
    Advances on pharmacogenomics of diuretics-related adverse reactions
    XING Kai, GONG Jinyu, LUO Jianquan
    2021, 26(2):  204-212.  doi:10.12092/j.issn.1009-2501.2021.02.012
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    Diuretics are the first-line drugs for the treatment of hypertension. Long-term use of diuretics often causes elevated blood sugar, electrolyte disturbances (most commonly hypokalemia), abnormal lipid metabolism (such as increased triglycerides, elevated cholesterol), increased serum uric acid levels and so on. In order to clarify the specific mechanism of the adverse reactions related to diuretics which are widely used in the treatment of hypertension, many documents have reported the pharmacogenomics research of diuretics-related adverse reactions. This review discusses the related genes and their variants of adverse reactions caused by commonly used diuretics in the treatment of hypertension in hope of providing a basis for the study of individualized use of diuretics.
    Management strategies and suggestions on stomatological clinical trials under the influence of epidemic
    ZHENG Lichun, WANG Xiang, WANG Wenmei
    2021, 26(2):  213-216.  doi:10.12092/j.issn.1009-2501.2021.02.013
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    Since the outbreak of Coronavirus Disease 2019 (COVID-19), a large number of clinical trials affected by the epidemic are suspended and postponed, and clinical trial institutions have initiated a series of emergency management measures. The characteristics of the diagnosis and treatment of stomatology are that the doctors and patients are closed to each other face to face, it is easy to produce droplets and aerosols, and there are many invasive operations, which leads to high risk of cross infection. The epidemic of COVID-19 poses a huge challenge to the operation of stomatological clinical trials. This paper based on the epidemic prevention and control requirements and the consensus on clinical trial management under major public health emergencies, combined with the relevant work guidelines of the institution and the relevant clinical trial regulations, puts forward suggestions on the clinical trial operation management and protective measures during the epidemic period. It may be helpful to the stomatological clinical trial researchers and subjects during the period of COVID-19.
    Current situation and future perspectives of treatment of chronic pulmonary aspergillosis
    WANG Nana, TAN Xiaofeng, MA Tao, CHENG Yusheng
    2021, 26(2):  217-222.  doi:10.12092/j.issn.1009-2501.2021.02.014
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    Chronic pulmonary aspergillosis (CPA) is a serious fungal infection, which complicates pulmonary tuberculosis, chronic obstructive pulmonary disease and sarcoidosis with high mortality. At present, the treatment of CPA include drug treatment and surgical treatment. The treatment plan should be determined by the type, clinical manifestations and surgical indications of the patients. Nevertheless, there is no standard plan, and more research is needed to improve it. Combined with the current literature reports, this article reviews the current and progress in the treatment of CPA.
    Research progress of thyroid dysfunctions during treatment with immune-checkpoint inhibitors
    MIN Hang, GUO Mengran, YE Yue, XU Xiaoshuang, ZHEN Donghu
    2021, 26(2):  223-229.  doi:10.12092/j.issn.1009-2501.2021.02.015
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    Thyroid dysfunction (TD) is one of the commonest endocrine immunotherapy-related adverse events (IRAEs) during cancer patients' treatment with immune checkpoint inhibitors (ICIs). In the hope that cooperation between departments will be enhanced to alleviate the side effect of immunotherapy which thyroid dysfunctions can cause, this review is contributed to make more endocrinologists and oncologists acknowledge and master clinical characteristics, diagnostic methods and therapeutic strategies of thyroid IRAEs, by the introduction of its pathogenesis, epidemiological features, diagnosis, treatment and prognosis.
    Progress in pharmacokinetics of polysaccharides
    XU Xin, WANG Rui, GAO Jian, PENG Jinyong, LI Hua, WANG Li
    2021, 26(2):  230-235.  doi:10.12092/j.issn.1009-2501.2021.02.016
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    Polysaccharide (PS) is one of the principal constituents in most traditional Chinese medicine. In recent years, the efficacy of PS has gradually become a popular aspect in fields of life science. Meanwhile, its pharmacokinetic research is still in its infancy. The classification, bioanalytical methods and pharmacokinetics of PS in recent years are summarized in this review. We hope to provide reference and guidance for researchers to study the pharmacokinetics of PS.
    Progress in research on hyperuricemia cell model
    WU Dan, DIAO Yong, XU Xianxiang
    2021, 26(2):  236-240.  doi:10.12092/j.issn.1009-2501.2021.02.017
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    High uric acid models are divided into animal models and cell models. Model construction is very important for hyperuricemia researching and drug screening. High uric acid animal model is mature, but there is a large gap between animals and humans, and animal models still have shortcomings. The cell model research cycle is short and the operation is simple. Meanwhile it is a model closer to human hyperuricemia, but it is rarely reported. This article briefly lists the cells commonly used in the construction of high uric acid models, outlines the construction methods of high uric acid cell models according to the two modeling principles of increasing uric acid synthesis and reducing uric acid excretion, and provides references for the development of hyperuricemia related research.