Table of Content

Volume 26 Issue 5
26 May 2021

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Pathophysiology and cognitive behavioral therapy of chronic insomnia

ZHAO Zhengqing, LI Yanpeng, XIANG Xiaoxia, ZHUANG Jianhua, ZHAO Zhongxin

2021, 26(5):  482-486.  doi:10.12092/j.issn.1009-2501.2021.05.001

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The occurrence and development of chronic insomnia involves subjective and objective factors, which can be classified as predisposing factors, precipitating factors and perpetuating factors. Cognitive behavioral therapy for insomnia (CBT-I) evolves from the pathopsychological analysis of chronic insomnia patients, and selectively combines the sleep hygiene, cognitive therapy and behavioral therapy to improve the symptoms of patients. With the popularity of internet, the digital cognitive behavioral therapy for insomnia has an convenient advantage over the traditional therapy, and has become the focus of research. Researchers have proposed multiple therapies for chronic insomnia, including drug therapy and non-drug therapy, which improve the treatment effect of chronic insomnia from different perspectives.

Progress in clinical diagnosis and drug treatment of chronic insomnia

LI Yanpeng, ZHAO Zhengqing, WANG Wenwen, ZHUANG Jianhua, ZHAO Zhongxin

2021, 26(5):  487-490.  doi:10.12092/j.issn.1009-2501.2021.05.002

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The clinical symptoms of chronic insomnia are various, the clinical diagnosis process needs to be combined with sleep parameters, daytime symptoms and psychological status of patients. Recently, the neuroimaging research suggests that chronic insomnia patients have certain structural changes and functional changes, which leads a new direction for the following research. The new drugs for the treatment of chronic insomnia, improving receptor specificity or increasing intervention targets, will provides more choices for patients.

Progresses in clinical manifestations and treatments of narcolepsy

WANG Mengmeng, ZHAO Zhongxin, WU Huijuan

2021, 26(5):  491-496.  doi:10.12092/j.issn.1009-2501.2021.05.003

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Narcolepsy is a rare disease that presents with sleep-wake disorder, which divided into narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). NT1 accounts for more than 75%, which is characterized by excessive daytime sleepiness (EDS), cataplexy attacks and nocturnal sleep symptoms (e.g. sleep paralysis, hallucinations, sleep disruptions, sleep movement disorders, etc.), accompanied by metabolic, psychiatric and emotional disturbances. The main clinical manifestation of NT2 is EDS, without cataplexy and nonspecific other symptoms of NT1. The treatments of narcolepsy mainly include the treatments of EDS and cataplexy, as well as the improvement of nocturnal sleep. This article will elaborate the advances in clinical manifestations and treatments of narcolepsy.

Clinical characteristics and standardized treatment of restless legs syndrome

ZHAO Xianchao, REN Jiafeng, SUN Shuyu, SU Changjun

2021, 26(5):  497-503.  doi:10.12092/j.issn.1009-2501.2021.05.004

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Restless legs syndrome is a common motor-sensory disease of the nervous system. The main manifestations are an urge to move the legs, usually accompanied by or thought to be caused by uncomfortable and unpleasant sensations in the legs. These symptoms may begin or worsen during periods of rest or inactivity such as lying down or sitting and be partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues. This article will systematically review the pathogenesis, clinical manifestations, diagnostic criteria, differential diagnosis and treatment of restless legs syndrome.

Progress in the diagnosis and treatment of rapid eye movement sleep behavior disorder

YUAN Yuan, ZHANG Yimeng, LI Ning, ZHAN Shuqin

2021, 26(5):  504-510.  doi:10.12092/j.issn.1009-2501.2021.05.005

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Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and rapid eye movement (REM) sleep without atonia. RBD is closely related to α-synucleinopathy disease, including Parkinson's disease (PD), Lewy body dementia (DLB) and multiple system atrophy (MSA). Many studies have discussed the markers, heredity, cognition, autonomic nervous function of RBD, and the predictive value for neurodegenerative diseases. This article reviews the research progress of early markers and treatments in recent years, and discusses future research directions.

Strategies for the treatment of circadian dysrhythmic sleep and wakefulness disorder

WU Wei, DENG Liying

2021, 26(5):  511-515.  doi:10.12092/j.issn.1009-2501.2021.05.006

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Circadian rhythm sleep-wake disorders (CRSWDs ) is a group of sleep-wake disorders caused by circadian rhythm disorder. Patients complain of difficulty in falling asleep, early waking, daytime drowsiness, which are often misdiagnosed and delayed for treatment. The American Academy of Sleep Medicine (AASM) updated the diagnostic criteria in 2014, and issued relevant treatment guidelines in 2015. In recent years, many countries have issued relevant clinical practice guidelines or consensus. The treatment of circadian rhythm sleep-wake disorder is different from the common sleep-wake disorder, with the focus on non-pharmacologic circadian rhythm regulation to reset the normal 24-hour sleep-wake rhythm. This article mainly introduces its treatment strategy and method.

Treatment of sleep disorder in patients with acute cerebrovascular disease

HUANG Yaqin, XUE Rong

2021, 26(5):  516-521.  doi:10.12092/j.issn.1009-2501.2021.05.007

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The high incidence of cerebrovascular disease and the high rate of disability cause a huge burden on the patient, family and society. The incidence of sleep disorder in acute cerebrovascular disease is high, which has an important effect on the prognosis of patients with cerebrovascular disease. This paper reviews the treatment of sleep disorder in patients with acute cerebrovascular disease, mainly acute ischemic cerebrovascular disease. 

Ursolic acid alleviates the injury of human aortic endothelial cells induced by high glucose and high fat#br#

LIU Xiaoling, SONG Zhenrong, FU Yuan, CHEN Min, SHI Ruizan, ZHANG Xuanping

2021, 26(5):  522-531.  doi:10.12092/j.issn.1009-2501.2021.05.008

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AIM: To investigate the effect and mechanism of ursolic acid on high glucose and high-fat injury of human aortic endothelial cells. METHODS: MTT method was used to select the appropriate injury concentration of high glucose and sodium palmitate and UA pre incubation concentration. The levels of NO and ROS, the release rate of lactate dehydrogenase and the activities of antioxidant enzymes including total superoxide dismutase, catalase and glutathione peroxidase were detected by kit. The expression of endothelial nitric oxide synthase, intercellular adhesion molecule, vascular cell adhesion molecule caspase-1 and GSDMD were detected by Western blot. The protective effect of UA on HAEC was observed. Hoechst33342 combined with PI fluorescence staining was used to detect the whole state of cell membrane to explore the occurrence of pyroptosis. RESULTS: Pre-incubation with UA (1 and 5 μmol/L) could reduce the damage of HAEC caused by high glucose and high fat (30 mmol/L Glu + 0.1 mmol/L SPA), enhance HAEC activity, increase NO release and eNOS protein expression, alleviate oxidative stress injury, reduce the protein expression of adhesion molecules and reduce the occurrence of pyroptosis. CONCLUSION: UA may reduce the damage of endothelial cells by inhibiting the oxidative stress response and the occurrence of pyroptosis induced by high glucose and high fat.

Gastrodin inhibits H₂O₂-induced ferroptosis of PC12 cells

WANG Youlin, LI Shanshan, WANG Meng, GUO Yuting, CHENG Hui, TIAN Shasha, LI Qinglin

2021, 26(5):  532-538.  doi:10.12092/j.issn.1009-2501.2021.05.009

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AIM: To investigate the protective mechanism of gastrodin against hydrogen peroxide (H2O2) damage in PC12 cells. METHODS: PC12 cells were treated with H2O2 to establish injury model, MTT assay was used to detect cell viability to establish the best suitable concentration of the model and the optimal treatment concentration of gastrodin were determined. Biochemical methods were used to analyze MDA, GSH and SOD activity. Flow cytometry were used to detect the change of ROS. Inverted transmission electron microscopy was used to observe PC12 cell morphology. Western blot was used to analyze the expression of p53, GPX4 protein. RESULTS: MTT assay showed that 50 μmol/L H2O2 inhibited PC12 cells after 48 h of treatment, while 1, 5, 25 μmol/L gastrodin cells reduced the inhibition of H2O2 on PC12 cells. MDA, GSH and SOD results showed that gastrodin reduced MDA level and increased SOD and GSH level after H2O2 treatment. Flow cytometry detection showed that gastrodin pretreatment reduced the content of intracellular reactive oxygen species after H2O2 injury. Transmission electron microscopy showed that the mitochondrial ridge was thicker and the mitochondrial volume was smaller in the 50 μmol/L H2O2 group than in the normal group, while the mitochondrial morphology tend to normal after gastrodin preconditioned PC12 cells. Western blot results showed that gastrodin could increase GPX4 protein expression and decrease p53 protein expression after H2O2 injury. CONCLUSION: H2O2 can cause ferroptosis by increasing the level of oxidative stress in PC12 cells, and gastrodin pre-protection can reduce the generation of oxidative stress and prevent ferroptosis which may be related to the up-regulation of GPX4 protein expression and down-regulation of p53 protein expression.

Vinpocetine improves the long-term cognitive function of infant rats induced by sevoflurane via Wnt/GSK3β/β-catenin signaling pathway

WU Wei, CHEN Zheng, DU Zhen, QU Shuangquan

2021, 26(5):  539-545.  doi:10.12092/j.issn.1009-2501.2021.05.010

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AIM: To explore the effect and mechanism of Vinfluoxine on long-term learning and memory function in infant mice.  METHODS: Sixty SD infant rats were randomly divided into Control group, Anesthesia group, Vinpocetine group (5 mg/kg), Vinpocetine group (10 mg/kg), GSK3β inhibition group (10 mg/kg) , with 12 infant rats in each group. Two hours before anesthesia, the infant rats in each group were injected with the corresponding drugs. Except for the control group, each group continued to inhale 4% sevoflurane for 4 hours. After 8 weeks, the Morris Water Maze experiments were started. Immunofluorescence double stains were used to detect neuronal proliferation in the brain. Western Blot was used to detect the protein expression in the hippocampus. RESULTS: There was no significant difference in the incubation period of the rats in the early training groups. On the third day of training, compared with the control group, the rats in the anesthesia group reached a significantly increased platform incubation period (P<0.05); In contrast, the intervention of vinpocetine and SB216763 significantly reduced the latency of rats to reach the platform (P<0.05). And in the test, compared with Anesthesia group, the 10 mg/kg vinpocetine and SB216763 intervention rats achieved a significant reduction in the latency of the first time to the platform (P<0.05), and the number of platforms crossing increased significantly (P<0.05). At the same time, sevoflurane anesthesia mediated a significant decrease in the number of BrdU/NeuN positive cells in rats (P<0.05). In addition, sevoflurane mediated a decrease in Wnt3a expression, an increase in p-GSK3β expression, and a decrease in β-catenin expression in the hippocampus (P<0.05). The intervention of vinpocetine and SB216763 significantly reversed the expression of these cells and proteins. CONCLUSION: Vinpocetine improves the long-term learning and memory function of sevoflurane anesthesia-induced infant rats through Wnt/GSK3β/β-catenin signaling pathway.

Protective effects of the extract from Toona sinensis seeds on gastric mucosa injury in experimental mice

LI Lihua, ZHANG Shengpeng, QIN Jiaxu, NIAN Sihui

2021, 26(5):  546-551.  doi:10.12092/j.issn.1009-2501.2021.05.011

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AIM: To study protective effects of the extract from Toona sinensis seeds on gastric mucosal injury in experimental mice.  METHODS: The mice were given 200 mg/kg, 400 mg/kg of Toona sinensis seeds every day for 2 weeks and ethanol or aspirin was used to induce gastric mucosa injury model. The gastric mucosal injury index and injury inhibition rate were calculated, the levels of SOD, MDA in serum and the contents of ET-1, PGE2 and NO in gastric mucosal tissues were determined to explore protective effects of Toona sinensis seeds on mucosa injury. RESULTS: After 14 days of prevention administration, Toona sinensis seeds could significantly reduce the gastric mucosa injury index induced by ethanol and aspirin. The inhibition rate of ethanol-induced gastric mucosa injury in the two dose groups was 40.4% and 47.4%, and that of aspirin -induced gastric mucosa injury was 38.9% and 44.6%. The inhibitory rate of cimetidine on ethanol and aspirin-induced gastric mucosa injury was 50.9% and 50.2%, respectively. In addition, compared with the model animal group induced by ethanol and aspirin, the doses of 200 and 400 mg/kg of Toona sinensis seeds could increase the levels of SOD, PGE2 and NO in the gastric mucosal tissues of mice, and reduce the contents of MDA and ET-1. CONCLUSION: The extract of Toona sinensis seeds has a certain protective effect on the injury of gastric mucosa in mice caused by ethanol and aspirin.

Population pharmacokinetics of capecitabine in Chinese breast cancer patients

XU Guofang, ZHANG Sisen, LIU Ping, MEI Jiazhuan, LIU Weiwei, LIU Ya'ou, QI Qi

2021, 26(5):  552-559.  doi:10.12092/j.issn.1009-2501.2021.05.012

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AIM: To investigate the population pharmacokinetic characteristics of capecitabine and its possible influencing factors in Chinese patients of breast cancer.  METHODS: 78 cases of Chinese patients with breast cancer were chosen as the objects in this study. Following treatment with capecitabine (0.6 g, 0.15 g/piece, 4 pieces, orally), blood samples were collected and concentrations of capecitabine in plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. The nonlinear mixed-effects software (NONMEM) was used to analyze the data and the population pharmacokinetic model was constructed accordingly. RESULTS: The final established model of absorption and elimination is one-compartment model. The clearance (CL/F) in pharmacokinetic formula of the model is as follows: CL/F=291×eηCL,i×(CCR÷93.1)0.47. The typical pharmacokinetic parameters of the model are as follows: the clearance (CL/F) is 291 L/h; the apparent volume of distribution (V/F) is 556 L; the absorption rate constant (Ka) is 1.05 h-1. In addition, the elimination of capecitabine can be notably influenced by creatinine clearance rate (CCR). CONCLUSION: The constructed model is stable, which fits features well of the population pharmacokinetics of capecitabine in Chinese patients with breast cancer. The modle can be utilized for the individualized administration plan in clinic.

Impact of China-US drug regulatory incentives on local innovative drug simultaneous development in multiple countries: An empirical study based on zanubrutinib

SHI Yingzi, ZHAO Yang

2021, 26(5):  560-569.  doi:10.12092/j.issn.1009-2501.2021.05.013

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This article teases out the main regulatory incentives for innovative drugs in China and US, including optimizing the processes, setting time limits for registration, expedited programs, R&D and evaluation communication and receiving clinical data from overseas. Meanwhile, case study method is used to analyze the impact of these regulatory incentives on BeiGene's zanubrutinib, which is the first drug from Chinese Innovation Company simultaneously developed in US and China. The results show that regulatory incentives are key factors to realize simultaneous development of zanubrutinib by shortening the time of registration in both countries and reducing the costs and risks of drug development. Other domestic companies can learn from the experience of zanubrutinib, to target unmet clinical needs, to rationally use domestic and foreign regulatory policies, and to enhance communication with regulators. Domestic regulator also can provide more suggestion to companies who have the intention to develop products abroad, so that more innovative drugs developed by local companies can be on the world stage.

Commonly used quantitative proteomics research techniques and their application in the study of pathogenesis of liver-derived diseases

SONG Ruzheng, PENG Ying, WANG Guangji, SUN Jianguo

2021, 26(5):  570-578.  doi:10.12092/j.issn.1009-2501.2021.05.014

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Proteomics is a subject with proteome as its research object. It is an important omics technology in the post-genomic era. Protein is the final product of gene expression. The overall study of protein expression is of great significance to the study of disease mechanisms and drug efficacy. Among them, quantitative proteomics has been widely used in recent years. The liver is the most important drug metabolism organ in the body, and more than 70% of drugs are metabolized by the liver. This article introduces the commonly used proteomics technology so far, as well as the progress of quantitative proteomics in drug-induced liver injury, non-alcoholic fatty liver disease, liver fibrosis and cirrhosis, hepatocellular carcinoma in the past five years.

Research progress of cytokines in wound healing

HE Xiujuan, MA Huike, LIU Qingwu, CHEN Jia, LIN Yan, LI Ping

2021, 26(5):  579-585.  doi:10.12092/j.issn.1009-2501.2021.05.015

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A variety of cytokines work synergistically to participate in wound healing. Although there are many studies on cytokines, the current clinical use of cytokines to treat wounds has not achieved the desired effect. The sequential administration of cytokines or the study of its drug delivery system may be its strategy to promote chronic wound healing. This article reviews the research progress of major growth factors, chemokines and inflammatory factors in wound repair in recent years.

Research progress in the treatment of depression with monome of Chinese herb, drug pairs, compound prescriptions and Chinese patent drugs

CHEN Ying, YUAN Yonggui

2021, 26(5):  586-593.  doi:10.12092/j.issn.1009-2501.2021.05.016

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Depression is a relatively common psychosomatic disease in clinical practice. It is mainly characterized by significant and lasting depression. It generally manifests as depression, loss of interest, impaired cognitive function, etc. Some patients are accompanied by somatization symptoms such as insomnia or lethargy, Loss of appetite, fatigue, loss of libido, etc. In severe cases, self-injury or even suicide may occur. According to research, depression has become the third leading cause of disability and death. At present, the pathogenesis of depression has not been definitively concluded, but a large number of studies have shown that it is related to biochemical, neuroendocrine, and neuroimmunological factors. At present, selective 5-HT reuptake inhibitors are routinely used in clinical treatment, such as sertraline, citalopram, Prozac, etc., but they often have slow onset and obvious side effects, making it difficult to achieve satisfactory therapeutic effects. Traditional Chinese medicine has gradually begun to be accepted by doctors and patients in the treatment of refractory diseases due to its multi-component and multi-target characteristics. This article mainly discusses the research progress of Chinese herbal extracts, Chinese herbal medicine pairs, Chinese herbal compound prescriptions, and Chinese patent medicines in the treatment of depression, and provides references for the clinical application of Chinese medicines in the treatment of depression.

Prospect of mesenchymal stem cell microvesicles repairing pelvic floor organ prolapse by antioxidant stress

HAN Qiaoling, PING Yi

2021, 26(5):  594-600.  doi:10.12092/j.issn.1009-2501.2021.05.017

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Pelvic organ prolapse (POP) is a common gynecological disease caused by pelvic floor fascia and ligament relaxation in middle-aged and elderly women. A large number of studies have shown that oxidative stress (OS) is one of the core mechanisms of POP. Mesenchymal stem cells (MSCs) are a research hotspot in regenerative medicine. Many evidences show that MSCs can play antioxidant properties in myocardial infarction, hyperoxic lung injury and other diseases，thus reducing inflammation and oxidative stress.In addition, microvesicles (MVs)derived from MSCs secreted can replicate the functions of MSCs through protein, mRNA, miRNA and lipid transport, and participate in many biological processes regulating tissue homeostasis and disease physiology and pathology. This article reviews the potential positive effects of MSCs-MVs in the treatment of POP through antioxidant stress.