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

Table of Content

    Volume 28 Issue 1
    26 January 2023
    Comparative study on the ability of active ingredients in Jinfukang to decrease neutrophils recruiting by lung cancer circulating tumor cells
    LIU Jiajun, QUE Zujun, TIAN Jianhui
    2023, 28(1):  1-9.  doi:10.12092/j.issn.1009-2501.2023.01.001
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    AIM: To observe the recruitment effect of lung cancer circulating tumor cells (CTCs) on neutrophils, and find out the effective components of Jinfukang in inhibiting the recruitment of neutrophils by CTCs.  METHODS: The ability of human lung adenocarcinoma circulating tumor cells CTC-TJH-01 cells to recruit neutrophils from whole blood leukocytes, and the effect of Jinfukang and its six active ingredients on the recruitment of neutrophils by CTCs was detected by flow cytometry. CCK-8 assay was used to observe cell viability to determine the concentration of action; transwell chemotaxis assay was used to detect the effect of six active ingredients on the chemotaxis of CTC-TJH-01 cells to neutrophils. RESULTS: CTC-TJH-01 cells could increase the recruitment of neutrophils compared to blank control (P<0.01); after the effect of Jinfukang, the neutrophils recruited by CTC-TJH-01 cells decreased (P<0.01). Trigonelline and Ophiopogonin D reduced neutrophil recruitment to CTC-TJH-01 cells at concentrations that had no effect on cell viability (P<0.01), trigonelline had the best effect; the chemotaxis of CTC-TJH-01 cells to neutrophils was weakened by trigonelline, astragaloside IV and Ophiopogon polysaccharide (P<0.05), and trigonelline had the best effect. CONCLUSION: Jinfukang can inhibit the recruitment of neutrophils by circulating tumor cells, and trigonelline, an effective monomer with "Fuzheng" effect in Jinfukang, can significantly inhibit the recruitment of neutrophils by circulating tumor cells in lung cancer, which proves that trigonelline may have the potential to inhibit lung cancer metastasis through targeting neutrophils.
    Pyroptosis mediated renal injury caused by chronic intermittent hypoxia and the intervention effect of edaravone in rats
    YANG Zhian, ZHAO Yan, HE Yao, LIU Weiying, YU Qin
    2023, 28(1):  10-18.  doi:10.12092/j.issn.1009-2501.2023.01.002
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    AIM: To study the protective effect of edaravone on renal injury induced by chronic intermittent hypoxia and its effect on Caspase-1 mediated pyroptosis signaling pathway in rats.  METHODS: Twenty four SPF male SD rats were randomly divided into normal control group, intermittent hypoxia group, intermittent hypoxia + normal saline group and intermittent hypoxia + edaravone group, with 6 rats in each group. The four groups of rats were placed in the closed feeding chamber for modeling. The oxygen concentration in the NC group was maintained at about 21%; the IH group, IH+NS group and IH+EDA group were given regular input of pure oxygen, pure nitrogen and compressed air to form anoxic-reoxygenation cycle (60 s hypoxic period + 60 s reoxygenation period). During the hypoxic period, the oxygen concentration in the chamber was reduced to 6%-7%, and the rats in the IH+EDA group were intraperitoneally injected with edaravone at a dose of 5 mg/kg per day before modeling, while the rats in the IH+NS group were intraperitoneally injected with normal saline at the same dose per day. After 8 weeks of modeling, blood and kidney tissue samples were collected to measure the levels of Crea and Urea in each group. The pathological changes and fibrosis degree of kidney were observed under light microscope after HE and Masson staining. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined by chemical method. The expression levels of NLRP3, Caspase-1 and IL-1β in renal tissues were determined by immunohistochemical staining. The expression levels of caspase-1 and IL-1β in renal tissues were determined by Western blot. GSDMD and IL-18 mRNA were detected by RT-PCR.RESULTS: After intermittent hypoxia exposure, serum Crea and Urea were increased significantly (P<0.01), renal tubules were damaged by pathology, collagen fiber deposition occurred in balloon space of renal units, MDA content was increased and SOD activity was decreased (P<0.01). Caspase-1, NLRP3, IL-1β protein expression increased (P<0.01 or P<0.05), GSDMD mRNA and IL-18 mRNA amplification increased (P<0.01); After Edaravone intervention, the above indexes showed a reverse trend compared with that after intermittent hypoxia exposure, and the pathological damage of kidney was reduced (P<0.01 or P<0.05). CONCLUSION: Chronic intermittent hypoxia may mediate kidney injury through oxidative stress activation of caspase-1 involved in the cell pyroptosis signaling pathway, while edaravone may inhibit the activation of pyroptosis signaling pathway by scavenging oxygen free radicals and down-regulating the level of oxidative stress in the body, thus playing a protective role in kidney. 
    Study on the improvement of Qingdaipowder Gel for external use on mice with specific dermatitis
    HUANG Yurong, ZHANG Hongqiang, YOU Rongli, JIA Ying, WANG Yan, FAN Jie, WANG Yingli
    2023, 28(1):  19-28.  doi:10.12092/j.issn.1009-2501.2023.01.003
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    AIM: To study the effect of Qingdaipowder Gel (QDPG) on mice specific dermatitis (AD) model and the antibacterial effect of the ethanol extract of Qingdaipowder.  METHODS: AD model of mice was established by repeated skin induction with 2,4-dinitrochlorobenzene (DNCB). Fifty-six mice were randomly divided into blank group, model group, Hydrocortisone Butyrate Cream group (Hyd, 1.5 mg/cm2), matrix group, high dose group of Qingdaipowder Gel (QDPG-H, 240 mg/cm2), medium dose group of Qingdaipowder Gel (QDPG-M, 120 mg/cm2), and low dose group of Qingdaipowder Gel (QDPG-L, 60 mg/cm2). For external use, the drug was administered to the skin once a day for 12 consecutive days. The skin lesions, auricle swelling, thymus and spleen index of mice in each group were analyzed. Hematoxylin eosin (HE) staining was used to observe the pathological changes of skin lesions, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum immunoglobulin E (IgE), interleukin-6 (IL-6), interleukin-4 (IL-4), and tumor necrosis factor α (TNF-α) and γ Interferon (IFN-γ) Level of inflammatory factors. Filter paper method and minimum inhibitory concentration (MIC) method were used to determine the antibacterial activity of the ethanol extract of Qingdaipowder against Staphylococcus aureus and Escherichia coli, the main pathogens of specific dermatitis. RESULTS: Compared with the model group, the degree of auricle swelling and the thickness of cortex in Hyd group and QDPG groups decreased significantly (P<0.01), and the serum levels of IL-4, IL-6, IgE, IFN-γ And TNF-α The level decreased significantly (P<0.01), IFN- γ/The ratio of IL-4 increased (P<0.05), and the thymus spleen index decreased (P<0.05) in QDPG-H group. The MIC values of the ethanol extract of Qingdaipowder against Escherichia coli and Staphylococcus aureus were 31.25 mg/mL and 62.5 mg/mL, respectively. CONCLUSION: QDPG can effectively alleviate the symptoms of specific dermatitis, and its mechanism of action can improve the skin lesions of AD model mice by inhibiting pathogenic bacteria and regulating the balance of T helper cells TH1/TH2.
    Effect of Atglistatin on PA-induced VSMCs proliferation and ATGL expression
    TANG Zizhao, NIE Fangqin, YAN Xin, FU Yangxia, HUANG Jun, WANG Xia, GUO Ren
    2023, 28(1):  29-35.  doi:10.12092/j.issn.1009-2501.2023.01.004
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    AIM: With building a proliferation model of PA-induced VSMC, the effect of ATGL, a key fat metabolism enzyme, on the phenotype transformation of VSMC was preliminarily explored.  METHODS: 40 μmol/L Atglistatin was added to the proliferation model of VSMC induced by PA (50 μmol/L, 100 μmol/L, and 200 μmol/L, respectively) at separately administered concentrations, and cell viability and cell proliferation were detected by CCK-8 and EDU; cell migration ability was detected by scratch assay; oil red staining was used to detect the accumulation of lipid droplets in VSMC was detected by oil red staining; the effects of PA on ATGL as well as the effects of smooth muscle contraction phenotype proteins were examined by Western blot. RESULTS: PA at a concentration of 100 μmol/L could significantly induce VSMC proliferation, promote lipophagy and increase lipid droplet accumulation in VSMC; meanwhile, Atglistatin could exacerbate these changes caused by PA and increase lipid droplet accumulation in VSMC.CONCLUSION: Atglistatin exacerbates PA-induced VSMC proliferation and increases VSMC lipid droplet accumulation, and exacerbates transformation of proliferative phenotype of VSMC.
    Involvement of autophagy in iron ion regulation promotes ferroptosis in cells undergoing intestinal ischemia-reperfusion injury
    ZHANG Jingyu, WANG Yihan, LI Jun, JIN Ping, SHEN Xiping, WANG Yingbin, LIU Jieting
    2023, 28(1):  36-41.  doi:10.12092/j.issn.1009-2501.2023.01.005
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    AIM: To investigate the effect of autophagy on cell ferroptosis in intestinal ischemia-reperfusion injury. METHODS: Twenty-four SPF grade Wistar rats weighing 200-220 g were divided into 4 groups (n=6): sham operation group (sham group), ischemia group (I group), ischemia-reperfusion group (I/R group),and ischemia-reperfusion+autophagy inhibitor group (I/R+3-MA group).The ischemia model was established by clamping the superior mesenteric artery for 1 hour, and the intestinal ischemia-reperfusion injury model was established by reperfusion for 2 hours. HE staining was used to observe the pathological changes of intestinal mucosa and Chiu score under light microscope. Fe2+ contents was measured by Colorimetric and LDH, LPO contents were measured by ELISA. FTH1, NCOA4, and LC3II/I expression by WB, and mitochondrial morphology was measured by transmission electron microscopy. RESULTS: Compared with the sham group, the remaining three groups had higher Chiu scores, FTH1 and NCOA4 were downregulated and LC3II/I was upregulated (P<0.01), LDH and Fe2+ were increased (P<0.01) in I and I/R, LDH (P<0.05), Fe2+ (P<0.01) were increased in I/R+3-MA group, the LPO content was elevated (P<0.01) in I/R; Compared with group I, the Chiu score (P<0.01), LDH, Fe2+ (P<0.05) and LPO (P<0.01) content were increased in group I/R (P<0.01), FTH1, NCOA4 was downregulated and LC3II/I was upregulated (P<0.01); Compared with the I/R, The Chiu score was decreased, the LDHand LPO (P<0.01), Fe2+ (P<0.05) content were decreased in I/R+3-MA, FTH1, NCOA4 was up-regulated and LC3II/I was down-regulated (P<0.01). Mitochondrial morphological changes: in sham group, intestinal tissue and mitochondria were intact, I group the mitochondrial cristae is reduced, and the double membrane structure is incomplete; in I/R group, the mitochondrial cristae was greatly reduced, and the organelle damage was serious. Increincrease in mitochondrial number and internal cristae were observed after 3-MA inhibition, and the membrane gradually became intact. CONCLUSION: In intestinal ischemia-reperfusion injury, autophagy participates in the regulation of cellular iron ions and promotes the occurrence of cell ferroptosis, and the inhibition of autophagy can reduce I/R intestinal injury.
    Effects of co-culture of dendritic cells loaded with MAGE-A3 antigen and cytokine-induced killer cells on tumor stem cells and malignant progression of endometrial cancer
    HUANG Hao, JIA Hong, WANG Xiaoshuang, ZHANG Lu, JIANG Hua
    2023, 28(1):  42-50.  doi:10.12092/j.issn.1009-2501.2023.01.006
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    AIM: To explore the effects of dendritic cells (DC) and cytokine-induced killer cells (CIK) carrying melanoma-associated antigen gene A3 (MAGE-A3) on endometrial cancer tumor stem cells and malignant progression.  METHODS: Human peripheral blood was collected to separate mononuclear cells, and DC and CIK cells were induced by cytokines, respectively. DCs were incubated with MAGE-A3 and then co-cultured with CIK, and the phenotypes of DC-CIK and MAGE-A3-DC-CIK were detected by flow cytometry; The CD133+ stem cells of the endometrial cancer cell line Ishikawa were sorted by flow cytometry, the endometrial cancer stem cells were used as target cells, and CIK, DC-CIK and MAGE-A3-DC-CIK were used as effector cells, respectively, MTT method was used to detect the cytotoxic activity of effector-target ratios of 10∶1, 20∶1 and 40∶1, ELISA method was used to detect IFN-γ, IL-2, IL-12 and IL-17 in the supernatant of the combined cultured cells, Annexin V-FITC/PI double staining was used to detect the apoptosis of endometrial cancer stem cells; A nude mouse model of endometrial cancer stem cell transplanted tumor was established, DC-CIK or MAGE-A3-DC-CIK was injected into the tail vein, and the tumor growth in nude mice was observed. The tumor size was measured every 2 days, after 21 days, the tumor tissue was taken and weighed on an electronic balance. HE staining was used to detect e the pathological changes of tumor tissues, and immunohistochemical staining was used to detect Ki-67 expression in tumor tissues. RESULTS: The expressions of CD80, CD86 and HLA-DR on the isolated DC surface were 88%, 86% and 90%, respectively. The ratios of CD8+CD3+ and CD56+CD3+ on the surface of MAGE-A3-DC-CIK group were higher than those of DC-CIK group (P<0.01); After sorting by magnetic beads, endometrial cancer stem cells with a proportion of CD133+ cells as high as 90.23% were obtained; Compared with CIK group and DC-CIK group, MAGE-A3-DC-CIK group has higher killing ability on endometrial cancer stem cells under different target ratios, the secretion level of IFN-γ, IL-2, IL-12, IFN-γ and IL-17 in the cell supernatant were increased, and the apoptotic rate of endometrial cancer stem cells treated with the culture medium supernatant was increased, the difference were statistically significant (P<0.01); At the same time, compared with the control group and DC-CIK group, the tumor volume of the transplanted nude mice in the MAGE-A3-DC-CIK group was smaller, the tumor weight was lighter, the cells in the tumor tissue were sparse, and the rate of Ki-67 positive cells was reduced, the difference were statistically significant (P<0.01). CONCLUSION: The co-culture of DC loaded with MAGE-A3 and CIK can promote the maturation of CIK, improve the lethality of endometrial cancer stem cells, and inhibit the malignant progression of transplanted tumor in nude mice.
    Quality management and indicator system for clinical trials of medical devices
    DAI Jiahui, SUN Sijia, XIE Xuefeng
    2023, 28(1):  51-58.  doi:10.12092/j.issn.1009-2501.2023.01.007
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    AIM: Exploring medical device clinical trial quality management indicator system to continuously improve medical device clinical trial quality system construction. METHODS: Through literature research and Delphi method, we summarized the risks of medical device clinical trials in various aspects such as quality management, clinical trial data, and clinical trial research personnel construction, analyzed the risks and proposed a clinical trial quality management index system, as well as corresponding quality improvement measures. RESULTS: To establish an appropriate medical device clinical trial quality evaluation management tool for quality risk monitoring and management, and to support and help the construction of a medical device clinical trial quality management system. CONCLUSION: To identify risks in various aspects of clinical trials and establish a preliminary assessment index system to provide a reference for the evaluation of the effectiveness of clinical trial quality management.
    Effects of esketamine combined with sufentanil on postoperative analgesia and emotion after thoracoscopic radical resection of lung cancer
    SU Yang, ZHOU Feng, DING Jinlei
    2023, 28(1):  59-65.  doi:10.12092/j.issn.1009-2501.2023.01.008
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    AIM: To observe the effect of Esketamine combined with sufentanil on analgesia and emotion after thoracoscopic radical resection of lung cancer. METHODS: A total of 108 patients undergoing thoracoscopic radical resection of lung cancer were randomly divided into three groups: Esketamine plus sufentanil patient-controlled analgesia group (S group), low-dose sufentanil patient-controlled analgesia group (LC group) and high-dose sufentanil patient-controlled analgesia group (HC group). PCIA was performed after operation. The formula of analgesia pump in group S: Esketamine 1.2 mg/kg, sufentanil 1 μg/kg, LC group analgesic pump formula: sufentanil 1 μg/kg; Formula of analgesic pump in HC group: sufentanil 1.5 μg/kg; Tropisetron 10 mg was added to three groups of analgesia pumps, and normal saline was diluted to 100 mL. Observe the visual analogue scale (VAS) and Ramsay sedation score of resting and exercise pain at 6 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) after surgery in both groups, evaluate and record the scores of SAS and SDS at 24 h (T0) before surgery, 24 h (T3), 48 h (T4), 72 h (T5) after surgery, and 7 d (T6) after surgery. Record the times of rescue analgesia, the times of effective pressing of the analgesia pump within 48 hours after operation, the times of ineffective pressing, and the occurrence of adverse reactions. RESULTS: In terms of anxiety, there was no difference in SAS scores among the three groups of T0. The SAS scores of T3 and T4 in S group and HC group were lower than those in LC group (all P<0.05). The SAS scores of T5 and T6 in the three groups were not statistically significant (all P>0.05); In terms of depression, the number of patients with depression in T0 group was not statistically significant (P>0.05), the number of patients with depression in T3, T4, T5 in AS group was less than that in LC group and HC group (P<0.05), and the number of patients with depression in T6 group was not statistically significant (P>0.05); In terms of analgesia, the VAS scores of rest and exercise in T1 group were not statistically significant (all P>0.05). The VAS scores of T2, T3, T4 in S group and HC group were lower than those in LC group (all P<0.05). The times of PCIA self-control and ineffective pressing in LC group within 48 hours after surgery were higher than those in S group and HC group (P<0.05). There was no significant difference in the times of pain relief in the three groups after surgery; In terms of adverse reactions, nausea, vomiting and skin itching in group S and LC were better than those in group HC (all P<0.05). There was no statistical significance in terms of sleepiness, respiratory depression, separation symptoms and nightmares in the three groups. CONCLUSION: Esketamine combined with sufentanil for postoperative analgesia after thoracoscopic radical resection of lung cancer can effectively reduce the scores of depression and anxiety of patients, with good analgesic effect and no increase in the incidence of adverse reactions.
    Exploratory study of the influence of respiratory microbiology on the efficacy of PD-1 inhibitors monotherapy for patients with advanced non-small cell lung cancer
    HUANG Xiaoming, DU Ye, LIN Shaoming, SHEN Guanle
    2023, 28(1):  66-74.  doi:10.12092/j.issn.1009-2501.2023.01.009
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    AIM: To investigate the implication of respiratory microbiology on the efficacy of PD-1 inhibitors monotherapy for patients with NSCLC.  METHODS: This study was designed as a retrospective study, fifty-eight patients with previously-treated advanced NSCLC who were received PD-1 monotherapy from October 2018 to October 2021 were included. The PD-1 inhibitors were consisted of camrelizumab, sintilimab and pembrolizumab. Additionally, the basic demographic data, therapeutic efficacy data, survival prognosis and adverse reactions during the PD-1 inhibitors treatment were collected and analyzed through the patients' medical records of the department and the electronic medical record system of the hospital. Furthermore, deep induced sputum specimens of the patients before treatment with PD-1 inhibitor were collected. And the respiratory microbiology of 58 samples were detected using 16S rRNA gene sequencing method. The index of respiratory microbiology α diversity was analyzed, and the correlation analysis was performed with the efficacy and prognosis of patients.RESULTS: A total of 58 patients with advanced NSCLC met the study's screening criteria and were evaluable for efficacy and safety profile. Efficacy data suggested that the objective response rate (ORR) and disease control rate (DCR) of the patients who received PD-1 inhibitors was 19.0%(95%CI: 9.9%-31.4%) and 55.2%(95%CI: 41.5%-68.3%). Furthermore, prognostic data obtained from follow-up indicated that the median PFS of the 58 patients with advanced NSCLC was 3.2 months (95%CI: 2.29-4.11) and the median OS was 10.5 months (95%CI: 5.58-15.43). Regarding the exploratory analysis between efficacy and respiratory microbiology, the 58 patients with NSCLC were divided into high α diversity group (group H) and low α diversity group (group L) according to Shannon diversity index of respiratory microecology detection. And the association analysis suggested that the ORR of patients with group H and group L was 23.3%and 17.9%(P=0.380), respectively. Furthermore, prognostic analysis indicated that the median PFS of patients with group H and group L was 3.8 and 2.8 months, respectively, which was statistically significant (P=0.034). CONCLUSION: PD-1 inhibitors monotherapy demonstrated preliminary efficacy and prognosis as subsequent line treatment for patients with advanced NSCLC. Patients with higher α -diversity of respiratory microbiology might confer a superior prognosis. And the conclusion should be validated in large sample prospective clinical trials subsequently.
    General considerations for clinical pharmacology of antitumor antibody-conjugated drugs: Implications from FDA review cases
    GAO Lili, WANG Yuzhu, WANG Yan, LI Jian, WANG Jun
    2023, 28(1):  75-85.  doi:10.12092/j.issn.1009-2501.2023.01.010
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    Antibody-drug conjugates (ADCs) are conjugated by a linker between an antibody drug targeting a specific antigen and a payload, such as a small cytotoxic drug. ADCs combine the potent killing effect of traditional small cytotoxic drugs with the tumor targeting property of antibody drugs. As of February 2022, the U.S. Food and Drug Administration (FDA) had approved 12 ADC anti-tumor agents. Based on the analysis of clinical pharmacology review reports of approved ADC drugs combined with relevant guidelines, it is found that in the development of ADC, in addition to the general research in clinical pharmacology, there are special considerations in dose selection and dose modification for special population due to the special anti-tumor mechanism of ADC. It is hoped that this paper will be enlightening to domestic researchers when developing ADC.
    Functions of CRABP2 in tumorigenesis and progression
    LIU Jiajia, GAO Yan, ZHANG Yehui, WU Jing
    2023, 28(1):  86-92.  doi:10.12092/j.issn.1009-2501.2023.01.011
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    Retinoic acid (RA) is a metabolic intermediate of vitamin A, which plays an important role in embryonic development and cell growth and differentiation. Cellular retinoic acid-binding proteins 2 (CRABP2) are a group of low-molecular weight intracellular proteins whose primary physiological function is to transport RA to the nucleus. Generally, CRABP2 binds to the retinoic acid receptor (RAR), then regulates specific downstream signaling pathways to function. Abnormal expression of CRABP2 was closely related to several human malignant tumors, and could affect the tumor occurrence and development through regulating multiple growth or apoptosis associated pathways or key biological molecules. Therefore, CRABP2 may be considered as a new diagnostic and prognostic marker for cancer, and a new therapeutic target for malignant tumors. Our present article summarizes the relationship between CRABP2 and tumor progression, drug resistance and prognosis, so as to provide reference for the future research.
    Role of the m7G methyltransferase METTL1 in tumours
    HONG Ziqiang, GOU Wenxi, CUI Baiqiang, BAI Xiangdou, JIN Dacheng, GOU Yunjiu
    2023, 28(1):  93-100.  doi:10.12092/j.issn.1009-2501.2023.01.012
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    N7-methylguanosine (m7G) is a common post-transcriptional modification of RNA that plays an important role in RNA processing, metabolism and function and is mainly regulated by the methyltransferase 1 (METTL1) and WD repeat domain 4 (WDR4) complexes. Several studies have shown that the METTL1/WDR4 complex promotes or inhibits the progression of many tumours, including head and neck tumours, lung, liver, colon, bladder and esophageal squamous cancers, which are dependent on m7G methylation modification of tRNA or miRNA. Therefore, METTL1 and m7G modification can be used as biomarkers or potential intervention targets, providing a new direction for early diagnosis and treatment of tumors. This article will mainly discuss the mechanism and corresponding research progress of METTL1 in tumorigenesis through m7G.
    Research progress on the relationship between hypoglycemic drugs and sarcopenia
    CAI Jing, PAN Binjing, LIU Jingfang
    2023, 28(1):  101-108.  doi:10.12092/j.issn.1009-2501.2023.01.013
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    Sarcopenia is a disease characterized by a decrease in muscle mass and function that can induce adverse events such as falls, weakness, and death. The latest research shows that the use of many hypoglycemic drugs is associated with sarcopenia. Different types of hypoglycemic drugs may have different effects and mechanisms for the quality and function of skeletal muscle. In this paper, we review the research progress of the relationship between hypoglycemic drugs and sarcopenia and the molecular mechanism in recent years to provide a reference for the diagnosis and treatment prevention of sarcopenia in clinical areas. 
    Research progress on signal pathways related to the pathogenesis of pancreatitis
    HUANG Huizhen, HAN Lei, LIN Xiaodong, CHEN Lei
    2023, 28(1):  109-113.  doi:10.12092/j.issn.1009-2501.2023.01.014
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    Pancreatitis is a common digestive disease, the main clinical symptoms are abdominal pain, emaciation, diarrhea, fatty diarrhea and so on. So far, the pathogenesis of pancreatitis has not been clarified, and there are few drugs with clear target, stable curative effect and fewer side effects. This paper summarizes the possible related signal pathways and related treatment methods of pathogenesis of pancreatitis, in order to provide new ideas and references for the research of new drugs for the treatment of pancreatitis.
    Research progress in the regulation of hypoxic pulmonary hypertension by hypoxia-inducible factor-1 signaling pathway
    SHEN Chang, AI Kelong, HU Changping
    2023, 28(1):  114-120.  doi:10.12092/j.issn.1009-2501.2023.01.015
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    Pulmonary hypertension (PH) is a rare and severe progressive disease. It results from hypertrophic remodeling of distal pulmonary arterioles that increases pulmonary arterial pressure and pulmonary vascular resistance in the absence of left heart, pulmonary parenchymal, or thromboembolic disease. Hypoxia-inducible factor-1 (HIF-1) regulates a large number of genes related to the occurrence and development of PH, and induces pulmonary angiogenesis, cell proliferation and migration, cellular energy metabolism and utilization. HIF-1 is an important component of the pathogenesis of hypoxic PH and plays an important role in driving the pathological process of pulmonary vascular and right ventricular remodeling. This article systematically elucidated the role and regulation of HIF-1 in hypoxic PH and its potential in targeted therapy of PH.