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

Table of Content

    Volume 27 Issue 12
    26 December 2022
    Research progress on the effect of noninvasive neuromodulation technique on patients with postoperative sleep disturbances after general anesthesia
    YANG Jie, CAO Junli, LIU He
    2022, 27(12):  1322-1332.  doi:10.12092/j.issn.1009-2501.2022.12.001
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    Noninvasive neuromodulation technique is a non-invasive, safe and convenient research and treatment method, which is mainly regulated by electrical stimulation and magnetic stimulation. In recent years, it has been more and more used in the research and treatment of brain function. It has been confirmed in the regulation of cognitive impairment, depression, anxiety, delirium and insomnia in patients with stroke. Clinical departments such as neurology, rehabilitation department, pain department and other disciplines have widely used this technique of non-invasive neural regulation, but its application in the perioperative period is less, especially for postoperative sleep disorders in patients with general anesthesia. Postoperative sleep disorder is a common and easily neglected complication, which is often manifested as postoperative sleep structure disorder, sleep quality decline, sleep is obviously shortened, and the sleep function of patients with general anesthesia is more likely to be affected. Postoperative sleep disorder includes many influencing factors before, during and after operation, affecting the whole perioperative period and even a few years after discharge.
    Research progress on effects of sevoflurane anesthesia on developing brain
    FAN Di, SHI Cuina, YANG Qingqing, JI Muhuo
    2022, 27(12):  1333-1339.  doi:10.12092/j.issn.1009-2501.2022.12.002
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    Sevoflurane is a commonly used inhalation anesthetic in children's general anesthesia, which may have some adverse effects on brain development. This review discusses the effects of sevoflurane anesthesia on developing brain, based on the characteristics of developing brain tissue, the effects on developing brain function, the mechanism of sevoflurane neurotoxicity and the strategies to reduce sevoflurane anesthesia neurotoxicity, so as to provide reference for clinical application.
    Effects of different doses of dexmedetomidine on non-cardiac surgery stress and postoperative sleep in patients with coronary heart disease
    YAN Lei, JIANG Haibin, NAFEISHA Paerhati, REZIWANGULI Yikemu, GENG Boyu, MAIERHABA Maimaitiaili
    2022, 27(12):  1340-1346.  doi:10.12092/j.issn.1009-2501.2022.12.003
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    AIM: To investigate the effects of different doses of dexmedetomidine on stress and postoperative sleep in patients with coronary heart disease (CHD). METHODS: Sixty patients with coronary heart disease undergoing endoscopic abdominal surgery were randomly divided into three groups (n=20): low-dose group (D1), high-dose dexmedetomidine group (D2) and control group (C) In groups D1 and D2, a loading dose of dexmedetomidine (0.5 μg/kg) was injected with intravenous pump for 10 min, followed by the maintain dose of dexmedetomidine 0.2 and 0.6 μg·kg-1·h-1 until 30 min before the end of surgery, respectively. The control group was given equal volume of normal saline. The scores of AIS on the first day before operation, the first day after operation and the third day after surgery were recorded. The mean arterial pressure (MAP), heart rate (HR) and the dosage of propofol and remifentanil during the surgery were recorded before anesthesia induction (T0), immediately after tracheal intubation (T1), immediately after pneumoperitoneum injection (T2), and immediately after extubation (T3). RESULTS: The AIS scores of the three groups were significantly higher than those before operation (P<0.05). MAP and HR at T1, T2 and T3 in D1 and D2 group were significantly lower than those in C group (P<0.05), and HR at T3 in D2 group was significantly lower than that in D1 group (P<0.05). The dosage of remifentanil and propofol in group D2 was significantly lower than that in group C (P<0.05). Compared with group D1 and C, the incidence of severe bradycardia was increased (P<0.05). CONCLUSION: Different doses of dexmedetomidine can reduce stress, stabilize hemodynamics and improve postoperative sleep of patients with coronary heart disease during non-cardiac surgery.
    Research progress of ketamine psychomimetic symptoms and reward mechanism
    YANG Hang, LU Fangzhou, YANG Chun, ZHU Wei
    2022, 27(12):  1347-1353.  doi:10.12092/j.issn.1009-2501.2022.12.004
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    Ketamine is a non-selective N-methyl-D-aspartic acid (NMDA) receptor antagonist. Ketamine plays a significant role in the treatment and research of neuropsychiatric diseases in recent years. The neural mechanism of ketamine psychogenic effects and reward pathway remains to be perfected, which may be closely related to a variety of neurons and pathways in the brain. This paper intends to review the relevant studies at home and abroad, and try to integrate the known neural mechanisms and put forward reasonable hypotheses.
    Research progresses in toxic effects and mechanism of anesthetics on the developing nervous system
    YAO Yiting, LIU Hanyu, WU Zifeng, WANG Di, YANG Chun, HUANG Chaoli
    2022, 27(12):  1354-1364.  doi:10.12092/j.issn.1009-2501.2022.12.005
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    Anesthesia is indispensable for surgery, but a growing number of studies have confirmed its toxic effects on the developing nervous system, and has attract increasing attentions from the scientific community. In this review, we briefly introduce the preclinical and clinical studies on the neurotoxic effects of anesthetic drugs on the developing brain, and summary the mechanisms from the aspects of molecular mechanisms (Ca2+ homeostasis, tau phosphorylation and m6A modification), subcellular structure (synaptic plasticity and mitochondrial dysfunction), neuroapoptosis and brain function, so as to provide a basis for guiding the use of anesthetics in clinical practice and improve the safety of infant anesthesia.
    Anesthetics, analgesics and cognitive function
    NI Yuanbo, ZHANG Xin, LI Yi, LIU Cunming
    2022, 27(12):  1365-1374.  doi:10.12092/j.issn.1009-2501.2022.12.006
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    Cognitive dysfunction has become a pivotal factor affecting the quality of life of elderly patients. The existing literatures can not explain the factors causing cognitive decline. Many researchers believe that anesthetics and analgesics may play important roles in cognitive dysfunction. This review will discuss the effects of different anesthetics and analgesics on cognitive function and briefly describe their mechanisms, so as to provide reference for the rational choice of medications in clinical practice.
    Effects of prolonged sevoflurane exposure on metabolomics of prefrontal cortex in aged mice
    HE Huan, XUE Zhenyu, MAO Haoli, ZHANG Lei
    2022, 27(12):  1375-1380.  doi:10.12092/j.issn.1009-2501.2022.12.007
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    AIM: To explore the effects of prolonged sevoflurane exposure on prefrontal cortical metabolites in aged mice using a metabolomics approach.  METHODS: Ten 18-month-old male C57BL/J6 mice were divided into a sevoflurane group (Sev group) and a control group (Con group) by the random number table method, with five mice in each group. Mice in the sevoflurane group were anesthetized with 3%sevoflurane and 60%oxygen for 6 h. Mice in the control group were given 60%oxygen under the same conditions for 6 h. All mice were executed immediately after the end of anesthesia or oxygenation, and fresh prefrontal cortex was taken for LC-MS/MS analysis. The data obtained were processed and analyzed using OSV2.1 software (AB SCIEX). RESULTS: Compared with the control group, the content of glutathione, arginine, coenzyme A, 1-methyl-histidine, L-arginino-succinate and 2-isopropylmalic acid was reduced in the prefrontal cortex of aged mice in the sevoflurane group, while the content of mesaconic acid was increased. A total of 29 metabolic pathways were involved in the differential metabolites, with significant enrichment in nine pathways including arginine biosynthesis. CONCLUSION: Significant changes in metabolites such as glutathione, arginine, and coenzyme A occurred in the prefrontal cortex of aged mice exposed to prolonged sevoflurane. The changes in these products may affect the amino acid metabolic pathway and the gluconeogenic pathway.
    Advance of general anesthetics-induced developing brain injury
    YANG Liu, LUO Ailin, LI Shiyong
    2022, 27(12):  1381-1390.  doi:10.12092/j.issn.1009-2501.2022.12.008
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    The effect of general anesthetics (GA) on the developing brain has been a research hotspot in the last two decades. Numerous studies have shown that GA could damage the developing brain and cause long-term cognitive impairment in the preclinical setting, while it remains controversial in the clinical context regarding this topic. In light of the limitations of directly translating the preclinical findings into clinical context, drawbacks of retrospective studies, lack of standard behavioral and mental assessing tools in clinical studies, and other confounding factors, it is difficult to gain an agreement on the issue. To improve the repeatability and persuasion of data in the field of GA-induced developing brain, we tried to integrally analyze the current status and progress of the topic and make it as reference for the related studies in the future. 
    Effects of different inhalation anesthetics on glial cells activation in neonatal rats
    ZHANG Jing, GAO Danyang, YU Kang, LIN Xiaowan, CAO Ying, LIU Xiao, MIAO Huihui, LI Tianzuo
    2022, 27(12):  1391-1399.  doi:10.12092/j.issn.1009-2501.2022.12.009
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    AIM: To examine the effects of three commonly used general anesthetics on the proliferation and activation of glial cells in neonatal rats. METHODS: Neonatal rats were exposed to either isoflurane, sevoflurane or desflurane for 2 h on postnatal day 2 (P2). The animals were euthanatized and the brain were harvested on P7 and P14, respectively. The immunohistochemical localization of glial markers (vimentin, GFAP, Iba1) were examined. RESULTS: Activation of astrocyte in granular layer and molecular layer of dentate gyrus of hippocampus was significantly enhanced on P7 and P14 after desflurane exposure, while that in isoflurane group the change was only significantly different on P14. The activation of microglia in the granular layer of dentate gyrus but not in the pyramidal cell layer of CA1 region was significantly enhanced in the desflurane group on P7 and P14, while the isoflurane group only showed significant difference on P14. CONCLUSION: Short time exposure of different inhalation anesthetics has different effects on the activation of glial cells in different subregions of hippocampus in neonatal rats on postnatal day 2, and sevoflurane may have the least effect on it.
    Research progress of anesthesia-related neural network in depth of anesthesia monitoring
    DING Jiahui, ZHOU Yu, YUAN Tianjie, XIA Junming, LI Wenxian, HAN Yuan
    2022, 27(12):  1400-1407.  doi:10.12092/j.issn.1009-2501.2022.12.010
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    Improper control of depth of anesthesia is not only detrimental to the rapid and stable recovery of anesthesia, but also affects the postoperative outcome of patients. Therefore, accurate control of anesthesia depth is an urgent clinical and scientific problem in the field of anesthesiology. At present, different algorithm models derived from electroencephalogram (EEG) signals are used to monitor the depth of anesthesia, but they cannot meet the requirements of anesthesiologists to accurately evaluate the depth of anesthesia. In recent years, the research on the mechanism and modulation of anesthesia-related neural network suggests that it has potential value as a method to monitor depth of anesthesia. Anesthesia-related neural networks mainly include sleep-wake circuit, thalamic-cortical circuit and corticocortical network. A thorough understanding of the neural network involved in the loss of consciousness caused by anesthesia will guide the depth of anesthesia monitoring more accurately and provide possibility for improving the quality of clinical anesthesia resuscitation.
    Evaluation of the effect of propofol and desflurane on intracranial pressure in patients undergoing gynecological laparoscopic surgery based on the ratio of diameter of optic nerve sheath to transverse diameter of eyeball
    ZHAO Xin, LI Ding, WU Anshi
    2022, 27(12):  1408-1413.  doi:10.12092/j.issn.1009-2501.2022.12.011
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    AIM: To evaluate the effects of propofol and desflurane on intracranial pressure in  patients undergoing gynecological laparoscopic surgery by measuring the ratio of optic nerve sheath diameter (ONSD) to transverse diameter of the eye (ETD).  METHODS: Forty patients, scheduled for elective gynecological endoscopic surgery, were randomly divided into propofol group (group P) and desflurane group (group D) (n=20). Anesthesia maintenance: propofol was injected intravenously in group P, desflurane was inhaled in group D. Remifentanil was injected intravenously and rocuronium was added on schedule. The patients were mechanically ventilated in volume-controlled mode. ETD was recorded after induction of anesthesia. ONSD, HR, MAP, peak airway pressure (Ppeak) and PETCO2 were recorded 5 min after induction of anesthesia (T0), 10 min (T1), 30 min (T2), 60 min (T3) after Trendelenburg position and after resuming the supine position (T4). ONSD/ETD values were calculated at different time points. RESULTS: Compared with T0, ONSD values of the two groups were increased at T2-T3 (P<0.05). ONSD value of group D was higher than that of group P at T2 (P<0.05). Compared with T0, the ratio of ONSD/ETD in group D was significantly increased at T1 (P<0.05). The ratio of ONSD/ETD in group D was significantly higher than that in group P at T1-T4 (P<0.05). Compared with T0, MAP in both groups was significantly increased at T1-T4 (P<0.05); Ppeak in both groups increased significantly at T1-T3 (P<0.05). MAP in group D was significantly lower than that in group P at T2-T3 (P<0.05). There was no significant difference in the incidence of postoperative adverse reactions between the two groups. CONCLUSION: In addition to remifentanil as anesthesia maintenance analgesic, intravenous injection of propofol or inhalation of desflurane can be safely used in gynecological laparoscopic anesthesia maintenance. Compared with desflurane, propofol maintenance can relieve the increase of intracranial pressure.
    Effect of erythrocytes, plasma proteins, and lysosomes on systemic exposure to tetrandrine and fangchinoline 
    LIAO Peiwei, WANG Wenxin, TIAN Nannan, ZENG Xueshan, REN Lingling, ZHU Yaxuan, JIA Weiwei, LI Chuan
    2022, 27(12):  1414-1424.  doi:10.12092/j.issn.1009-2501.2022.12.012
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    AIM: The Chinese medicinal herb Hanfangji is dried roots of Stephania tetrandra S. Moore (Family, Menispermaceae). Tetrandrine and fangchinoline are two major constituents of Hanfangji and these bisbenzyltetrahydroisoquinoline alkaloids possess anti-cancer and other pharmacological activities. To facilitate further pharmacodynamic investigation of these compounds, a pharmacokinetic investigation was performed in rats and in vitro. METHODS: Pharmacokinetics of tetrandrine and fangchinoline were characterized in rats p.o. or i.v. dosing an aqueous extract of Hanfangji or the individual compound. Unbound levels of systemic exposure to these two alkaloids were assessed using in vitro studies of plasma protein binding, blood-plasma partition, and lysosomal trapping. All the study samples were analyzed by liquid chromatography/mass spectrometry.RESULTS: We found two pharmacokinetic features of tetrandrine and fangchinoline. First, the two compounds had blood levels of systemic exposure substantially higher than the respective plasma levels of systemic exposure. Second, the two compounds exhibited significantly higher systemic exposure levels after p.o. dosing an aqueous extract of Hanfangji than the respective exposure levels after p.o. dosing the individual compound, at the same compound dose levels and under the same conditions for analytical measurement and the same conditions for animal study. Unbound fractions of tetrandrine and fangchinoline in rat plasma were 2%-5%and the concentrations of the alkaloids in rat erythrocytes were 5-times higher than those in rat plasma. Lysosomal inhibitor could block their trapping in lysosomes and significantly reduce their concentrations in HEK-293 cells. CONCLUSION: The following pharmacokinetic aspects should be noted in pharmacodynamic investigation of tetrandrine and fangchinoline: extensive binding with plasma proteins, extensive binding with erythrocytes, and trapping by lysosomes of tissue cells substantially reduce the levels of unbound tetrandrine and fangchinoline in the systemic circulation. 
    Effect of esketamine and butorphanol on morphine-induced pruritus after cesarean section: A randomized controlled clinical study
    FENG Yan, LI Gaowei, JIN Qiqi, CAI Weicha, LIN Xuezheng, LI Jun
    2022, 27(12):  1425-1430.  doi:10.12092/j.issn.1009-2501.2022.12.013
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    AIM: To evaluation the effects of esketamine and butorphanol on postoperative pruritus induced by epidural morphine injection in cesarean delivery parturients.  METHODS: A total of 162 parturients who underwent elective cesarean section under continuous epidural anesthesia in Taizhou Central Hospital (Taizhou University Hospital), were selected and randomly divided into esketamine group (group K), butorphanol group (group B) and blank control group (group C). 5min after umbilicus amputation, parturients in group K was injected with 3 mg morphine diluent through epidural catheter, and esketamine 0.2 mg/kg intravenously. Parturients in groups B and C were given the same dose of morphine,and butorphanol 10 μg/kg or the same volume of normal saline, respectively. The incidence of postoperative pruritus at different times, the degree of pruritus and incidence of other adverse reactions were compared among three groups. RESULTS: The highest incidence of pruritus occurred within 4 hours after operation. The incidence of postoperative pruritus at 4 hours in group K and B was significantly lower than that in group C (3.7% vs. 3.7% vs. 29.6%, P<0.05), the total incidence of postoperative pruritus within 48 hours was also significantly lower than that in group C (13.0% vs. 11.1% vs. 40.7%, P<0.05), and the incidence of moderate to severe pruritus was also significantly lower than that of group C (5.6% vs. 3.7% vs. 31.5%, P<0.05). There was no significant difference between group K and group B (all P>0.05). There were no significant differences in the incidence of postoperative nausea, vomiting, dizziness and postoperative pain scores among three groups (P>0.05). CONCLUSION: Both esketamine and butorphanol can reduce the incidence and degree of pruritus caused by epidural morphine injection in parturients, without affecting the analgesic effect of morphine and without increasing the incidence of adverse reactions. Esketamine is as effective and safe as butorphanol in preventing pruritus after cesarean section.
    Research progress on human immunodeficiency virus-associated pulmonary arterial hypertension
    MENG Shi, WANG Zhongqun
    2022, 27(12):  1431-1440.  doi:10.12092/j.issn.1009-2501.2022.12.014
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    Human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) is a long-term cardiovascular complication of AIDS patients, with an incidence of about 0.5%. The onset of HIV-PAH is insidious and lack of specific symptoms with poor prognosis. The pathogenesis is complicated while the bystander effect of HIV or the complication of HIV is possible mechanism. Echocardiography is an important diagnostic method and facilitates early screening of patients. At present, there is no specific drug targeted HIV-PAH, and the treatment strategy is to follow the treatment recommendations for idiopathic pulmonary arterial hypertension on the basis of highly active antiretroviral therapy, while the interaction between two types of drugs should be considered. This paper will mainly focus on the pathogenesis and treatment of HIV-PAH.