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

Table of Content

    Volume 29 Issue 4
    26 April 2024
    Analysis of the effect of fudosteine on induced sputum components in patients with stable neutrophil-dominated COPD
    LI Zhanbo, DU Kaifeng, JIANG Zhilong, GAO Jiameng, CHEN Mengjie, MA Yuan, CHEN Zhihong
    2024, 29(4):  362-369.  doi:10.12092/j.issn.1009-2501.2024.04.001
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    AIM: To observe the effect of fudosteine on induced sputum cell components and lung function in patients with stable neutrophil-dominated COPD. METHODS: From October 2019 to October 2022, 53 patients with stable COPD were selected and divided into fudosteine group and placebo group. The placebo group was treated with routine treatment, and the fudosteine group was treated with fudosteine on the basis of routine treatment. The two groups were treated for 6 months. The clinical symptoms [Saint George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Modified British Medical Research Council Dyspnea scale (MMRC), Breathlessness, Cough, and Sputum Scale (BCSS)], lung function index, induced sputum cytology analysis and other related examination results were recorded in detail before and after treatment. RESULTS: (1) Compared with the baseline, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) of the two groups were improved after treatment, and the differences were statistically significant (P<0.05). However, after treatment, there was no significant difference in pulmonary function between the two groups except for the percentage of carbon monoxide diffusion in the predicted value (DLCO%pre) (DLCO%pre in the fudosteine group was higher than that in the placebo group). (2) After treatment, the total number of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group. Compared with the number of cells in each component at baseline, the total number of induced sputum cells and neutrophil count in the fudosteine group were significantly lower (P<0.05). CONCLUSION: Fudosteine treatment in patients with stable neutrophil-dominated COPD can improve lung function, reduce the total number of induced sputum cells and the total number of neutrophils, thereby improving airway inflammation. 
    Induced sputum testing in chronic airway disease and the prospects for its development
    GAO Jiameng, SHEN Yao, XUE Liping, CHEN Zhihong
    2024, 29(4):  370-376.  doi:10.12092/j.issn.1009-2501.2024.04.002
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    Induced sputum testing is a non-invasive test that reflects the nature and extent of airway inflammation and plays an important role in the diagnosis, treatment and prognosis of chronic airway diseases. This article outlines the development history of induced sputum technology, introduces the principle and operation of induced sputum technology, evaluates its safety, summarizes the three main test components, elaborates the role of this technology in various chronic airway diseases, such as reflecting the type of airway inflammation, predicting the efficacy of medication, and combining it with transcriptomics to study disease mechanisms, and briefly summarizes its innovations and makes a vision for the future.
    Targeted biotherapy for chronic obstructive pulmonary disease
    BAI Haodong, SHA Bingxian, Ambedkar Kumar Yadav, XU Xianghuai, YU Li
    2024, 29(4):  377-382.  doi:10.12092/j.issn.1009-2501.2024.04.003
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    Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease. The current status of treatment based mainly on bronchodilators and ICS is not sufficient for all of COPD patients. Various studies have attempted to use biologics targeting specific cytokines and their receptors in COPD patients to alleviate respiratory symptoms or reduce the risk of acute exacerbations. However, they failed to bring significant clinical benefits. More studies are needed to further determine the efficacy of targeted biotherapy for COPD.
    Mechanism and treatment of mucous hypersecretion in chronic obstructive pulmonary disease
    ZHANG Ting, SUN Rong, YANG Yong, LIU Weichun, YUAN Yuping, JU Xu, WANG Qian
    2024, 29(4):  383-391.  doi:10.12092/j.issn.1009-2501.2024.04.004
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    Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchoscopy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.
    Clinical features, risk factors and treatment of type 2 diabetes mellitus in patients with acute exacerbation of chronic obstructive pulmonary disease
    WANG Xiaochuan, WANG Hanchao, YAO Yu, LI Li, HE Gaoyan, LI Bo, ZHU Tao
    2024, 29(4):  392-400.  doi:10.12092/j.issn.1009-2501.2024.04.005
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    AIM: To investigate the clinical features of acute exacerbation chronic obstructive pulmonary disease (AECOPD) of complicated with type 2 diabetes mellitus (T2DM) , and analyze the related clinical features and risk factors. METHODS: This was a single-center cross-sectional study. From March 2020 to January 2023, 479 hospitalized patients with AECOPD in the department of respiratory and critical care medicine, Suining Central Hospital were included. There were 215 patients in AECOPD group and 60 patients in AECOPD with T2DM group. The collected variables included demographic data, complications, blood routine, infection index, random blood glucose, blood gas analysis and lung function. The adoption rate and constituent ratio of the basic description classification data were expressed as mean standard deviation for the normal distribution measurement data and median interquartile range for the skew distribution measurement data. T-test was used for normal distribution and non-parameter test was used for non-normal distribution. The categorical variables were tested by chi-square test. Rank sum test was used for rank variable data. Binary logistic regression model was used to investigate the independent factors associated with T2DM in patients with AECOPD. Finally, the results of logistic regression were verified and visualized by nomogram, validation curve, ROC curve and DCA curve. P<0.05 was a significant statistical difference. RESULTS: Univariate analysis showed that there were significant differences in body mass index (BMI), essential hypertension, coronary heart disease, atrial fibrillation (AF), pulmonary function (GOLD stage), blood neutrophil (NS), blood lymphocyte (LYM), arterial blood gas PaCO2, Alanine transaminase (ALT) and random blood glucose (RBG) between the two groups (P<0.05). The binary logistic regression model (C-index=0.847) was constructed with the above 10 variables, the results showed that BMI (OR=1.309), Af (OR=8.188), LYM counts (OR=0.474), PaCO2 (OR=1.082) and RBG (OR=1.434) were independently associated with type 2 diabetes in patients with AECOPD (all P>0.05). The results of logistic regression were verified and visualized by Nomogram and its-associated ccurves. The MAE and AUC curves were 0.021 and 0.847 respectively, indicating that the model had good prediction consistency and accuracy. The DCA curve showed that Nomogram's risk threshold ranged from 0.01 to 0.99, suggesting that nomogram's model had better clinical predictive value. CONCLUSION: Our results showed that increased BMI, PaCO2 and random glucose, decreased blood lymphocyte, and atrial fibrillation is an independent clinical feature of AECOPD with T2DM. These results suggest that the immune function of patients with AECOPD and T2DM are more severely impaired and more likely to be accompanied by atrial fibrillation, which is a potential cause of poor prognosis in these patients. Meanwhile, this conclusion needs to be further verified in multicenter study with large sample size.
    Navafenterol, a new drug for the treatment of chronic obstructive airway disease
    LIU Yuru, WU Wenwen, WANG Gang
    2024, 29(4):  401-405.  doi:10.12092/j.issn.1009-2501.2024.04.006
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    Navafenterol is a new compound with both muscarinic receptor antagonist and β2 receptor agonist effects in a single molecule, who is being developed for the treatment of chronic obstructive airway disease such as chronic obstructive pulmonary disease and asthma. These pilot clinical studies found that it can significantly improve lung function and symptoms, and is safe and well tolerated. Common treatment emergent adverse events include headache, nasopharyngitis, and dizziness. It may become a next-generation bronchodilator for chronic obstructive airway disease. This review introduced the prospective of Navafenterol.
    Progress and prospect of inhaled biological agents in asthma
    LI Guanghui, HUANG Jing, ZHU Min, ZHAO Rui, WAN Yakun, CHEN Zhihong
    2024, 29(4):  406-414.  doi:10.12092/j.issn.1009-2501.2024.04.007
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    More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5%-10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of biopharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.
    Immunologic characteristics and management and prospects of targeted biological therapy in adults with severe asthma
    SUN Ao, WANG Jingluan, LIU Wenjuan, REN Dunqiang, LIU Xiaojing
    2024, 29(4):  415-422.  doi:10.12092/j.issn.1009-2501.2024.04.008
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    Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding of asthma's pathophysiology deepens, a beacon of hope emerges in the form of biological targeted therapies, offering a promising avenue for the management of this challenging condition. These therapies, by precisely inhibiting or modulating pivotal molecules in the inflammatory cascade, offer potential benefits in symptom alleviation, lung function enhancement, and risk reduction of acute exacerbations. They signify a paradigm shift in severe asthma treatment. Within the confines of this article, we embark on a systematic exploration of the immunological underpinnings that define severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.
    Value of biotargeted drugs in airway mucus therapy of asthma
    MOU Duo, LIU Kexin, CHANG Chun
    2024, 29(4):  423-426.  doi:10.12092/j.issn.1009-2501.2024.04.009
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    Airway mucus plug is a common phenotype in asthma that increases the risk of acute asthma attacks by causing aggravation of airflow obstruction. Given its important role in asthma, treatment targeting airway mucus plugs may be a strategy to control asthma progression and prevent fatal asthma exacerbations. Previous studies have shown that acidosophils and T2 type inflammation are related with the formation of mucus plugs, and biotargeted drugs targeting the above pathways may be effective in the treatment of airway mucus plugs.
    Progress in the application of AIT in allergic airway diseases
    WANG Linlin, MA Yuan, CHEN Zhihong, JI Haiying
    2024, 29(4):  427-431.  doi:10.12092/j.issn.1009-2501.2024.04.010
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    Allergen specific immunotherapy (AIT) is to identify the patient's allergen, give the patient repeated exposure to the allergen extract, and gradually increase the concentration and dose until the target maintenance dose is reached, so that the patient can develop tolerance to the allergen, which is the only treatment that can regulate the pathogenesis of allergic diseases and change its natural course. In recent years, domestic and foreign scholars have made great progress in the clinical practice and research field of AIT. This article reviewed the relevant progress of the mechanism, efficacy and drug administration of AIT.
    Use of central neuromodulators in chronic cough
    SHA Bingxian, BAI Haodong, LI Wanzhen, YU Li, XU Xianghuai
    2024, 29(4):  432-439.  doi:10.12092/j.issn.1009-2501.2024.04.011
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    Chronic cough is a common condition that imposes significant physical, psychological, and social burdens on patients. Although chronic cough is often associated with underlying conditions such as asthma, gastroesophageal reflux disease, and eosinophilic bronchitis, some patients experience uncontrollable coughing that is difficult to attribute to a specific cause. Many of these patients exhibit clinical features of cough hypersensitivity syndrome, providing new directions for research into the treatment of chronic cough. As the pathophysiological mechanisms of chronic cough are further elucidated, treatment approaches for chronic cough are entering a new stage of development. This article summarizes and discusses the mechanisms and clinical evidence of central neuromodulators used in the treatment of chronic cough, suggesting promising clinical applications for these drugs in the future.
    Effects of gastrodin on the expression of BDNF and IL-6 in the striatum of rats with cerebral ischemia
    LIU Min, DING Yanxia, ZHANG Yegui, CHAN Cuicui, GONG Rujie, NI Jingzhong
    2024, 29(4):  440-446.  doi:10.12092/j.issn.1009-2501.2024.04.012
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    AIM: To investigate the effect of gastrodin on the expression of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the striatum of cerebral ischemia rats, and to explore the potential mechanism of gastrodin in treating cerebral ischemia. METHODS: The rats were randomly divided into four groups: normal, sham, model, and gastrodin groups, each consisting of 10 rats. After successful modeling using middle cerebral artery occlusion (MCAO), the gastrodin group received intraperitoneal injection of gastrodin injection at a dose of 10 mg/kg once a day for 14 consecutive days. Pathological changes in striatal neurons were observed using Nissl staining. Immunohistochemistry was utilized to detect positive expression of BDNF and IL-6 proteins in the striatum. Additionally, immunoblot analysis was performed to determine the expression levels of BDNF and IL-6 proteins in the striatum. RESULTS: Nissl staining revealed clear and intact structures of striatal neurons in the normal and sham groups, with tightly arranged cells. In the model group, the number of cells was significantly reduced compared to the sham group (P<0.01), and there was a noticeable cytosolic atrophy and loose cell arrangement. The gastrodin group showed a significant increase in the number of Nissl-positive neurons compared to the model group (P<0.01), and there was also a significant improvement in cell morphology. The results of immunohistochemistry and immunoblot were consistent, and there was no statistically significant difference in BDNF and IL-6 protein expression between the normal group and the sham group (P>0.05). Compared to the sham group, the model group showed a decrease in the protein expression level of BDNF in the striatum on the ischemic side (P<0.01) and an increase in the protein expression level of IL-6 (P<0.05, P<0.01). In contrast, the gastrodin group showed an increase in the protein expression level of BDNF in the striatum on the ischemic side (P<0.05, P<0.01) and a decrease in the protein expression level of IL-6 (P<0.05, P<0.01) compared to the model group. CONCLUSION: Gastrodin has a significant protective effect on striatal injury caused by cerebral ischemia, and its mechanism may be related to the up-regulation of the anti-inflammatory factor BDNF and the down-regulation of the pro-inflammatory factor IL-6.
    Effect of radix scutellariae microemulsion gel on chronic eczema in mice model
    WANG Ke, NIU Chenbing, CHANG Yinxia, QIN Xuemei, LUAN Zhihua, ZHANG Yue
    2024, 29(4):  447-454.  doi:10.12092/j.issn.1009-2501.2024.04.013
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    AIM: To prepare radix scutellariae microemulsion gel and investigate its therapeutic effect on chronic eczema based on the previous research of radix scutellariae self microemulsion. METHODS: The gel matrix and humectant were optimized by single factor method and response surface method to obtain the formula and preparation technique of the gel. The Franz diffusion cell method was used to evaluate the transdermal properties of microemulsion and microemulsion gel in vitro. By establishing a chronic eczema model in the mouse ear, the swelling degree, swelling inhibition rate, pathological changes and tumor necrosis factor α (TNF-α), Interleukin-1β (IL-1β) and interleukin?6 (IL-6) of radix scutellariae microemulsion gel were measured, to investigate the therapeutic effect on chronic eczema in mice. RESULTS: The physical and chemical properties of radix scutellariae microemulsion gel were stable. Compared with microemulsion, the microemulsion gel had better transdermal performance. The cumulative transdermal amount of baicalein and wogonin, the main components of microemulsion gel, was 1.85 times and 2.77 times of that of microemulsion respectively. Moreover, the steady flow rate and permeability coefficient of microemulsion gel significantly increased, and the lag time significantly shortened. Pharmacodynamic study showed that compared with the model group, the radix scutellariae microemulsion gel could significantly reduce the ear swelling of mice (P<0.05), and the serum inflammatory factor TNF-α, IL-1β and IL-6 reduced content by over 37%. Compared with the radix scutellaria aqueous extract and aqueous extract gel, the treatment of chronic eczema was better. CONCLUSION: The preparation process of radix scutellaria microemulsion gel is feasible, with strong transdermal property, and a significant therapeutic effect on chronic eczema.
    Investigation and analysis of the current status of clinical research nurses
    CHEN Liming, ZHANG Haiyan, HUANG Fan, ZHAO Wenyan, DING Rui, CAO Cai, FANG Yi
    2024, 29(4):  455-459.  doi:10.12092/j.issn.1009-2501.2024.04.014
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    AIM: To investigate and analyze the current situation and needs of clinical research nurses in China, in order to provide scientific basis for constructing a training system for research nurses, promoting standardized training, and achieving standardized management for them. METHODS: A self-made questionnaire was used to investigate 102 research nurses from nearly 70 well-known clinical trial institutions in China. The contents of the questionnaire mainly included the general information, professional experience and work content of the research nurses, the sense of accomplishment and training needs of clinical trial work. RESULTS: Among the 102 research nurses surveyed, 92.15% have a bachelor's degree or above; 53.92% of those have intermediate or higher professional titles; 74.51% of them are part-time research nurse. Among professional experiences, 19.61% have more than 10 years of clinical trial experience; 47.06%, 40.20%, and 21.17% of surveyed research nurses were authorized to participate in clinical trial drug management, sample management, and quality control; 70.59% of research nurses have a high sense of achievement in their daily work. In terms of education and training needs, clinical trial related laws and regulations, standardized training for clinical trial protocol implementation, and good clinical practice (GCP) are the three most important aspects. CONCLUSION: Clinical research nurses in China have a relatively high level of education and nursing experience, but there is still a large gap in the amount of professional full-time clinical research nurses in China. Due to the rapid development of innovative drugs and devices, as well as the urgent need to improve the clinical research system, it is necessary to establish a training, assessment, and evaluation system for research nurses that is in line with China's national conditions in order to improve the professional level of research nurses, and improve the quantity and quality of clinical trial research on innovative drugs and devices in China.
    Predictors of curative effect of Quyin Koufuye and its synergistic effect on biologics in the treatment of psoriasis
    DU Juan, LIN Lanmei, DONG Canbin, YAN Kexiang, GAO Jian
    2024, 29(4):  460-465.  doi:10.12092/j.issn.1009-2501.2024.04.015
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    AIM: To assess the efficacy of Quyin Koufuye in different types of psoriasis vulgaris and analyzes the relationship between efficacy and various disease-related factors, as well as its complementary role in biologic therapy. METHODS: This study included a total of 396 patients with psoriasis.Based on the patient history, participants were categorized into the biologics group (n=98), Quyin Koufuye-assisted biologics group (n=62), and Quyin Koufuye monotherapy group (n=236). Patient history data were collected, including gender, duration of illness, disease type, initial site of onset, degree of itching, recurrence status and time, smoking habits, joint pain, family history of psoriasis, nail damage, treatment plan, and PASI/BSA scores. A retrospective analysis was conducted to identify factors influencing the efficacy of Quyin Koufuye and to analyze its combined effects with biologics. RESULTS: Combining Quyin Koufuye with biologics significantly boosted the PASI90 response rate to 72.6% (P=0.014). Responders to PASI50 with Quyin Koufuye experienced longer recurrence intervals (>6 months) than non-responders (50% vs. 33.6%, P=0.045). Influencing factors included psoriasis-affected body surface area (OR=0.960, P=0.000), prolonged smoking history (OR=2.10, P=0.046), and psoriasis type (OR=2.47, P=0.015). CONCLUSION: This study underscores the synergy of Quyin Koufuye and biologics in treating psoriasis, particularly for longer recurrence intervals-factors like smoking history, psoriasis type, and affected body surface area impact Quyin Koufuye's efficacy. 
    Research progress on the role of circular RNA in neonatal hypoxic-ischemic encephalopathy
    DANG Yinxia, SHEN Fuhui, WANG Shengxia, LU Xia, WANG Fan
    2024, 29(4):  466-474.  doi:10.12092/j.issn.1009-2501.2024.04.016
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    Hypoxic-ischemic encephalopathy (HIE) is a major cause of newborn mortality and childhood disability. Despite hypothermia treatment being the current standard method, it has its limitations and often produces unsatisfactory outcomes. Additionally, due to time and equipment constraints, hypothermia treatment cannot be promptly administered, leading to high mortality rates or varying levels of neurological impairments even after treatment. Hence, the exploration of alternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology.Research has shown that HIE induces intricate changes in the neurological system at the physiological, cellular, and molecular levels. Circular RNA (circRNA) exhibits high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes. Therefore, circRNA holds promise as a potential therapeutic target for HIE. This article provides a comprehensive overview of the regulatory effects of circRNA on different types of neural cells in HIE, aiming to offer new theoretical foundations for the treatment of HIE.
    Progress in the potential therapeutic mechanism of mesenchymal stem cell-derived exosomes for liver fibrosis
    ZHAO Tingting, LI Junfeng, ZHANG Liting
    2024, 29(4):  475-480.  doi:10.12092/j.issn.1009-2501.2024.04.017
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    Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.