南京中医药大学学报

Modern Interpretation of the Scientific Connotation of the Pathogenesis of Cancerous Toxin

CHENG Hai-bo, ZHOU Zhong-ying

2021, 37(5): 637-641. doi: 10.14148/j.issn.1672-0482.2021.0637

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Abstract:
Pathogenesis theory of cancerous toxin is an innovative theory of traditional Chinese medicine oncology developed by the team, which has been widely used to guide the clinical differentiation and treatment for malignant tumors in recent years, and has achieved good clinical efficacy. Cancerous toxin is a specific pathogenic factor that causes malignant tumors and is the key pathogenesis for the development of malignant tumors. The team has been conducting research on the scientific connotation of pathogenesis of cancerous toxin for a long time. Through exploring the relationship between pathogenesis theory of cancerous toxin and tumor microenvironment as well as the correlation between pathogenesis of cancerous toxin and specific morbid substances in tumor microenvironment, the team comes up with that the scientific connotation of cancerous toxin is a specific morbid substance (affecting tumor genesis and development) in tumor microenvironment. In addition, the team also believes that inflammatory factors, lactic acid, angiogenic factors, immunosuppressive factors, and non-coding RNAs may be the biological basis for the pathogenesis of cancerous toxin. Applying modern oncology research progress, we interpret the scientific connotation of the pathogenesis of cancerous toxin, and provide scientific basis for further promotion of the theory of cancerous toxin and its clinical application.

From "Experience" to "Evidence": Evidence-Based Medicine Facilitates the Inheritance and Innovation of Traditional Chinese Medicine

DONG Fei, LIU Jian-ping

2021, 37(5): 642-647. doi: 10.14148/j.issn.1672-0482.2021.0642

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Evidence-based medicine (EBM) has been introduced and disseminated in China for over two decades, with milestone achievements made in traditional Chinese medicine (TCM) research. Based on the analysis of the connotation of evidence-based Chinese medicine, this paper briefly combs the current situation and challenges of the development of evidence-based Chinese medicine, and summarizes that evidence-based Chinese medicine is beset with "four surpluses" and "four shortages". According to a new understanding of the EBM methodological system (including methodology and basic research approaches), this paper also puts forward suggestions on conducting clinical TCM research based on evidence-based practice, with a view to promoting TCM's transformation from "experience" to "evidence", exerting TCM's original advantages, and driving TCM's inheritance, innovation, and development.

Analysis on the Translational Medicine Research Ideas and Methods of Traditional Chinese Prescription Guided by Clinical Value

CHENG Xiao-lan, WANG Qian, YUAN Fei-fei, CUI Xiao-ying, ZHANG Wen-juan, CAO Peng

2021, 37(5): 648-653. doi: 10.14148/j.issn.1672-0482.2021.0648

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Abstract:
Traditional Chinese prescription is the main form of clinical medication of traditional Chinese medicine (TCM), and also the important carrier of TCM inheritance and innovation. Because of the bottle-neck problems such as unclear chemical basis, unclear function mechanism, unstable quality control and lack of evidence-based medicine, traditional Chinese prescription has been questioned frequently. It is difficult for traditional Chinese prescription to gain international approval, and its clinical application and industrial development are very limited. How to carry out the basic research of traditional Chinese prescription scientifically and effectively for better clinical application has become an urgent problem to be solved in the development of TCM. In recent years, the rising and developing of translational medicine has brought new opportunities and ideas for the innovation and development of TCM. This paper briefly described the difficulties in the clinical application and development of traditional Chinese prescription, discussed the present situation and the main problems in the translational research of TCM, and further condensed the research ideas and methods, with the purpose to provide beneficial guidance for the further research of TCM.

"Compound-Delivery-Efficacy" Characterization Idea of External Chinese Medical Properties Based on Biopharmaceutical Thoughts

CHEN Jun, YAO Jun-hong, WANG Yi-wei, GU Wei, YAN Guo-jun, ZHANG Xiao-dong, DUAN Jin-ao

2021, 37(5): 654-657. doi: 10.14148/j.issn.1672-0482.2021.0654

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Abstract:
Characterization of Chinese medical properties is the key basis for guiding modern study in drug property discovery. However, lack of appropriate guidance limits current studies of external Chinese Medicine(CM). Based on the study progress of Chinese medical properties and the characteristics of external CM, three key elements of "component-delivery-efficacy" are proposed based on biopharmaceutical thoughts. Using such characterization model, drug delivery can be firstly regarded as the key factor between the component and the efficacy under the external route. Under the guidance of "compound-delivery-efficacy", essential oils (EOs) from herbs with "hot" property was found to possess higher penetration enhancement effect compared to other properties. The results revealed the rationale of the proposed three-element theory. This theory may lead a new strategy in scientific research, clinical application, and development of external CM products.

Reflections on the Establishment of an Integrated Speculation System in Traditional Chinese Medicine

LIU Yu-liang, LI Ru-hui, TAO Lin

2021, 37(5): 658-661. doi: 10.14148/j.issn.1672-0482.2021.0658

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Abstract:
Syndrome differentiation and mechanism observation are the keys to the traditional Chinese medicine (TCM) clinical practice. They are also crucial to the improvement of clinical efficacy. This study gives a detailed explanation of the speculation system of syndrome differentiation and mechanism observation: speculating according to the chronological order of occurrence and development of diseases and syndromes (vertical speculation), along with speculating on the elements of syndromes and mechanism in an appositive way (horizontal speculation). In addition, the differentiation and analysis of the various influencing factors of syndromes and diseases are supplements to the combination of the vertical and horizontal speculations. The collection and analysis of the four diagnostic information form the basis of that combination speculations. Besides, we propose the dynamically integrated relationship of speculation on the complex mechanism and the speculation model of syndrome differentiation and mechanism observation by incorporating modern scientific methods. Thus, it has a certain guidance value for the research of the theory of syndrome differentiation and mechanism in TCM.

Efficacy of Nasal Administration of Bikangfu in the Treatment of Chronic Rhinosinusitis in Children

WU Zi-lu, LI Jing-bo, CAI Ji-tang, WANG Jun-jie, XU Xin-ming

2021, 37(5): 662-668. doi: 10.14148/j.issn.1672-0482.2021.0662

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Abstract:
OBJECTIVE To investigate the clinical efficacy of nasal administration of Bikangfu in the treatment of chronic rhinosinusitis in children.METHODS A total of 168 children with chronic rhinosinusitis were randomly divided into observation group and control group, 84 cases in each group. The observation group was given nasal administration of Bikangfu therapy, the control group was given Tongqiao Biyan granules combined with Sinupret drops orally. The course of treatment was four weeks. The changes of visual analog scale (VAS) symptom score, symptoms and signs scores of rhinosinusitis in traditional Chinese medicine, Lund-Mackay score of nasal sinus CT were observed in patients treated before and after treatment. The levels of nasal secretions and serum inflammatory factors including prostaglandin D₂ (PGD₂), leukotriene C4 (LTC4), interleukins (IL-17, IL-33), eosinophil cationic protein (ECP), and immunoglobulin (IgE) were measured before and after treatment in the two groups.RESULTS After treatment, the VAS score, traditional Chinese medicine symptoms and signs scores, and Lund-Mackay score of nasal sinus CT in the two groups were decreased significantly compared with those before treatment (P < 0.05, P < 0.01), while the results in the observation group were better than those the control group (P < 0.05, P < 0.01). The total effective rate after treatment was better in the observation group than that in the control group (P < 0.01). In addition, the levels of PGD₂, LTC4, IL-17, IL-33, ECP, and IgE in the serum and nasal secretions in both groups were lower than those before treatment (P < 0.05, P < 0.01), while the results in the observation group were better than those in the control group (P < 0.05, P < 0.01). Besides, there was no obvious adverse reaction occurred in the two groups after treatment.CONCLUSION With no adverse reaction, nasal administration of Bikangfu therapy can effectively reduce the clinical symptoms of children with chronic rhinosinusitis. Its mechanism of action may be related to the regulation of inflammatory factors in serum and nasal secretions.

Efficacy of Thunder-Fire Moxibustion Combined with Sijunzi Decoction in the Treatment of Chronic Pharyngitis with Lung and Spleen Qi Deficiency and the Effect on the Level of Inflammatory Factors and Immune Factors

ZHANG Tian-tian, SUN Mai-qing

2021, 37(5): 669-672. doi: 10.14148/j.issn.1672-0482.2021.0669

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OBJECTIVE To observe the efficacy of thunder-fire moxibustion combined with Sijunzi decoction in the treatment of chronic pharyngitis with lung and spleen qi deficiency and the effects on the levels of inflammatory factors and immune factors.METHODS A total of 60 patients with chronic pharyngitis of lung and spleen qi deficiency were randomly divided into observation group and control group, 30 patients in each group. The observation group was treated with thunder-fire moxibustion combined with modulated Sijunzi decoction, while the control group was given conventional western medical treatment. There were four courses of treatment, seven days per course. In addition, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), immunoglobulin A (IgA), immunoglobulin E (IgE), and secretory immunoglobulin A (SIgA), Chinese medicine syndrome scores and clinical efficacy were observed before and after treatment in the two groups.RESULTS After treatment, Chinese medicine syndrome scores of the two groups improved significantly (P < 0.05, P < 0.01), while the result in the observation group was better than that in the control group (P < 0.05, P < 0.01). The levels of inflammatory factor IL-6, TNF-α, and immune factor IgE decreased, while the levels of immune factor IgA and SIgA increased in the two groups (P < 0.01). However, the results in the observation group were better than those in the control group (P < 0.05, P < 0.01).CONCLUSION Thunder-fire moxibustion combined with modulated Sijunzi decoction treatment can significantly reduce the pharyngeal symptoms in patients with chronic pharyngitis with lung and spleen qi deficiency. The mechanism is related to reducing the levels of inflammatory factor IL-6, TNF-α, and immune factor IgE, increasing the levels of immune factor IgA and SIgA, enhancing systemic immunity, as well as improving the local environment.

Evaluation of the Effect of Suxiao Jiuxin Pills on Myocardial Damage in Acute STEMI with Qi Stagnation and Blood Stasis Based on Intracoronary Electrocardiogram

YANG Yue-dong, WU Li-xing

2021, 37(5): 673-677. doi: 10.14148/j.issn.1672-0482.2021.0673

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OBJECTIVE To evaluate the effect of Suxiao Jiuxin pills on myocardial damage in acute ST-segment elevation myocardial infarction (STEMI) with qi stagnation and blood stasis based on intracoronary electrocardiogram.METHODS 60 acute STEMI patients with qi stagnation and blood stasis who underwent percutaneous coronary intervention (PCI) directly from March 2019 to February 2020 at Integrated Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine were selected. Besides, according to the random number table, these patients were divided into the control group and the study group, with 30 cases in each group. The two groups were given standard preoperative treatment, while based on that, the study group was given sublingual administration of Suxiao Jiuxin pills. The clinical efficacy of traditional Chinese medicine (TCM), as well as TCM syndrome score and adverse reactions were compared between the two groups after one week of treatment. In addition, the value of ST-segment resolution (ΔIST) of intracoronary electrocardiogram combined with the blood flow of thrombolysis and thrombin inhibition in myocardial infarction (TIMI) were compared after PCI.RESULTS The TCM clinical efficacy and ΔIST in the study group were significantly higher than those in the control group (P < 0.05), while the TCM syndrome scores of both groups were decreased significantly (P < 0.01). In addition, the syndrome scores of chest distress, distention and fullness in the chest and hypochondriac region, as well as spontaneous sweating in the study group were significantly lower than those in the control group (P < 0.05). However, there was no statistical difference in the postoperative TIMI flow grades and adverse reactions between the two groups (P>0.05).CONCLUSION Preoperative administration of Suxiao Jiuxin pills can further reduce myocardial damage, alleviate clinical symptoms, and enhance the TCM clinical efficacy without increasing adverse reactions in patients with acute STEMI with qi stagnation and blood stasis.

Exploring the Correlation between Syndrome Differentiation of Traditional Chinese Medicine of Non-Ischemic Cardiomyopathy and Myocardial Fibrosis Based on Cardiac MRI

CHEN Hai-xiong, LI Min-yan, DU Yong-xing, LIN Qiu-hong, HU Qiu-gen, YANG Shao-min

2021, 37(5): 678-681. doi: 10.14148/j.issn.1672-0482.2021.0678

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OBJECTIVE To investigate the correlation between syndrome differentiation of traditional Chinese medicine (TCM) of non-ischemic cardiomyopathy (NICM) and parameters of the cardiac volume and function, along with myocardial fibrosis.METHODS We selected 64 patients clinically diagnosed with NICM from September 2019 to October 2020 at Shunde Hospital of Southern Medical University. The patients were divided into three groups according to TCM syndrome differentiation, including the syndrome of stasis obstructing the heat blood, syndrome of turbid phlegm obstruction, as well as the syndrome of neither stasis obstructing the heat blood nor turbid phlegm obstruction (heart yang insufficiency, heart-kidney yin deficiency, deficiency of both qi and yin, and cold congealing heart vessel). All patients underwent cardiac magnetic resonance (CMR), which includes black-blood sequence, bright-blood sequence, and late gadolinium enhancement (LGE). The CMR bright-blood sequence images were post-processed to obtain parameters of cardiac volume and function, including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular stroke volume index (LVSVI), left ventricular cardiac output index (LVCOI), and left ventricular mass index (LVMI). The LGE left ventricular images were divided into 17 segments according to the American Heart Association (AHA) recommendations and were classified into grades one to three according to the segmental distribution of abnormal ventricular wall enhancement. In addition, statistical analysis was performed on the above data.RESULTS The differences were statistically significant (P < 0.05) when comparing the LVEF in the turbid phlegm obstruction group and neither stasis obstructing the heat blood nor turbid phlegm obstruction groups. The differences were statistically significant (P < 0.05, P < 0.01) when comparing the LVEDVI in the turbid phlegm obstruction group, the stasis obstructing the heat blood group, as well as neither stasis obstructing the heat blood nor turbid phlegm obstruction groups. The differences were statistically significant (P < 0.01) when comparing the LVESVI in the turbid phlegm obstruction group and neither stasis obstructing the heat blood nor turbid phlegm obstruction groups. The difference was statistically significant (P < 0.05) when comparing myocardial fibrosis degree in the stasis obstructing the heat blood group with the turbid phlegm obstruction group.CONCLUSION The TCM syndrome differentiation of NICM has some correlation with parameters of the cardiac volume and function as well as myocardial fibrosis degree. Thus, this study provides new ideas for objective research and new methods for revealing the essence of Chinese medicine through the semi-quantitative and quantitative study of TCM syndrome differentiation combined with modern magnetic resonance technology.

Adenosine-Mediated Cardioprotection of Local Cyclical Compression on Neiguan on Myocardial Ischemic Rats

XU Sen-lei, GU Ren-jun, YANG Xue-ying, BIAN Xiang-yu, XU Xin, XIA Xue-feng, SUN Ke, WU Jia-hong, LIU Yu-chen, LU Sheng-feng, ZHANG Hong-ru, GU Yi-huang

2021, 37(5): 682-687. doi: 10.14148/j.issn.1672-0482.2021.0682

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OBJECTIVE To observe the effect of cyclic mechanical compression of Neiguan (PC 6) on myocardial infarct size and cardiac function in rats with myocardial ischemia, and to preliminarily investigate the possible mechanism by which this factor produces cardioprotective effects.METHODS A total of 18 adult male SD rats were randomly divided into sham, model, and mechanical stimuli group, 6 rats in each group. The myocardial ischemia model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model and mechanical stimuli group, while threading but not ligating at LAD was applied in the sham group. In the mechanical stimuli group, the Neiguan (PC 6) was pressed by the self-made instrument, with a contact surface of 3 mm diameter circular silica gel head and a force of 150 g, and the pressing mode was 5 min of pressing and 5 min of relaxation, with 3 cycles as one group, with intervention once a day for 3 consecutive days. The TTC staining was used to measure myocardial infarction area. Left ventricular ejection fraction(LVEF)was measured by echocardiography. The myocardial expression of IL-1β, IL-6 and TNF-α were detected by Western blot. Serum adenosine concentration was detected by ELISA. The expression level of adenosine deaminase(ADA)in acupoints was detected by immunohistochemistry.RESULTS Compared with sham group, myocardial infarction area of model group increased(P < 0.001), LVEF value decreased(P < 0.001), and there was no difference in serum adenosine content and ADA expression in acupoint area (P>0.05). Compared with model group, the myocardial infarction area and myocardial expression of IL-1β, IL-6 and TNF-α in mechanical stimuli group decreased (P < 0.01), LVEF value increased (P < 0.001), serum adenosine content increased (P < 0.01), and the expression level of adenosine deaminase in acupoints decreased (P < 0.05).CONCLUSION Cyclic mechanical compression of Neiguan (PC 6) can reduce the infarct size and improve cardiac function in Myocardial ischemic rats. The mechanism may be related to mechanical stimuli limiting adenosine degradation by inhibiting the expression of ADA in acupoint, contributing to cardioprotection via increased adenosine concentration in the artery.

Experimental Study on the Safety of Hypertime Window Thrombolysis for Cerebral Infarction by Inhibiting the Activation of Astrocytes with Acupuncture

XU Wen-tao, JIANG Si-yuan, CHANG Si-qi, ZHANG Zhi-hui, SONG Yang-yang, ZHANG Xin-chang, NI Guang-xia

2021, 37(5): 688-695. doi: 10.14148/j.issn.1672-0482.2021.0688

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OBJECTIVE To observe the effect of acupuncture on the safety of hypertime window thrombolysis in rats with acute cerebral infarction, and to explore its mechanism from the way of astrocytes.METHODS Cerebral infarction model was prepared by improved autoembolism method in rats. "Xingnao Kaiqiao" acupuncture was used as interventional method, and rt-PA was injected through caudal vein as thrombolysis method. 66 SD rats were randomly divided into sham operation group, model group, 4.5 h thrombolysis group, 6 h thrombolysis group, acupuncture+4.5 h thrombolysis group and acupuncture+6 h thrombolysis group, with 11 rats in each group. Bederson method was used to evaluate the neurobehavioral scores of rats at the 2nd and 24th hour after modeling. TTC staining method was used to compare the cerebral infarct volume percentage of rats in each group, EB osmotic method was used to compare the blood-brain barrier (BBB) permeability of rats in each group, and dry-wet weight method was used to measure the brain water content of rats in each group. 48 SD rats were randomly divided into sham operation group, model group, 6 h thrombolysis group and acupuncture+6 h thrombolysis group, with 12 rats in each group. The qPCR and Western blot were used to detect the mRNA and protein expressions of astrocyte-related indexes glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4) in the cerebral cortex of rats in each group.RESULTS Compared with the sham operation group, the neurobehavioral score, percentage of cerebral infarct volume and brain water content in the model group significantly increased (P < 0.01). The neurobehavioral scores, percentage of cerebral infarct volume and brain water content in the 4.5 h thrombolysis group and the acupuncture+4.5 h thrombolysis group were lower than those in the model group (P < 0.01). Compared with the model group and the 6 h thrombolytic group, the neurobehavioral score, the percentage of cerebral infarct volume and brain water content in the acupuncture+6 h thrombolytic group significantly decreased (P < 0.05, P < 0.01). The mRNA and protein expression levels of GFAP and AQP-4 in model group were significantly higher than those in sham group (P < 0.05, P < 0.01). The mRNA and protein expression levels of GFAP and AQP-4 in acupuncture+6 h thrombolysis group were significantly lower than those in model group and 6 h thrombolysis group (P < 0.05, P < 0.01).CONCLUSION Acupuncture can inhibit the activation of astrocytes by down-regulating the expression of GFAP and AQP-4, thus improve the safety of hypertime window thrombolysis in cerebral infarction.

Effects of Electroacupuncture Preconditioning on Cardiac Dysfunction and Inflammatory Response in LPS-Induced Sepsis Mice

CHEN Li-yao, YANG Wen-xiu, SHI Jun-jing, YANG Jia-li, FU Shu-ping, YU Mei-ling, LU Sheng-feng

2021, 37(5): 696-701. doi: 10.14148/j.issn.1672-0482.2021.0696

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OBJECTIVE To investigate the effects of electroacupuncture (EA) pretreatment on cardiac dysfunction and inflammatory reaction in lipopolysaccharide (LPS)induced sepsis mice, and to explore the possible mechanisms of EA preconditioning for cardioprotection.METHODS A total of 24 male C57BL/6J mice were randomized into 3 groups: control group, model group, and EA pretreatment group, with 8 mice in each group. Before modeling, mice in the EA pretreatment were given "Zusanli" (ST36) EA stimulation (2/15 Hz, 2 mA, 15 min)under anesthesia with isoflurane. The model group and the control group were only fixed for 15 min in the same way. The sepsis mice models were established by intraperitoneal injection of LPS (10 mg/kg). Similar to the control group, an equal volume of saline was administered. Cardiac function was measured by echocardiography and the contents of inflammatory cytokines in serum was examined by ELISA. The mRNA and protein expression levels of inflammatory cytokines in cardiac tissue were detected with qPCR and Western blot respectively, the number of F4/80⁺CD11b⁺macrophages and the contents of F4/80⁺CD11b⁺CD206^low M1 and F4/80⁺CD11b⁺CD206^high M2 macrophages in myocardium was determined by flow cytometry.RESULTS Compared with the control group, the LVEF, LVFS value of the model group was decreased (P < 0.01), the serum levels of TNF-α, IL-1β increased (P < 0.01), the expression of TNF-α, IL-1β, IL-6, IL-10 mRNA and protein increased (P < 0.01, P < 0.05), the number of F4/80⁺CD11b⁺macrophages in cardiac tissue increased (P < 0.01), the proportion of F4/80⁺CD11b⁺CD206^low M1 macrophages increased (P < 0.01). Nevertheless, EA pretreatment group could reverse these changes mentioned above in the model group. Compared with the model group, the LVEF, LVFS values increased significantly (P < 0.01), the serum levels of TNF-α, IL-1β decreased (P < 0.05, P < 0.01), the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and the number of macrophages in the myocardium downregulated (P < 0.05, P < 0.01), the expression of anti-inflammatory interleukins IL-10 (P < 0.05) and the proportion of M2 macrophages in the myocardium upregulated (P < 0.01).CONCLUSION EA preconditioning may promote the polarization of macrophages in myocardial tissue from M1 pro-inflammatory macrophages to M2 anti-inflammatory macrophages, reduce the level of systemic and local inflammation, improve heart function, and produce myocardial protection.

Effects of Senescent Hepatocytes Exosomes on Inflammatory Chondrocytes Induced by LPS and Intervention Effect of Paeonia Lactiflora

ZHANG Li, LI Xiao-chen, LIAO Tai-yang, WANG Pei-min, XING Run-lin

2021, 37(5): 702-708. doi: 10.14148/j.issn.1672-0482.2021.0702

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OBJECTIVE To explore the effects of senescence hepatocellular exosomes on LPS-induced chondrocytes and the intervention effect of Paeonia lactis.METHODS The primary hepatocytes of mice were extracted and the optimal concentration of the decoction of Paeonia lactis was selected by CCK-8. Subsequently, liver cells were randomly divided into the normal group, the senescence group and the Paeonia lactide group. The senescence of liver cells was induced by 0.3 mm hydrogen peroxide, and the gene and protein expressions of p16, p21 and p53 were detected to observe the senescence of liver cells and the intervention effect of Paeonia lactis. Exosomes were extracted from the supernatant of liver cells in each group, and identified by electron microscopy, particle size analysis, and tetrapod CD9, CD63, CD81. Chondrocytes were cultivated in mice, the content of TNF-α and IL-1β in cell supernatant were determined with or without LPS. The intake of chondrocytes were observed by PHK67 dye marker, and LPS-induced chondrocytes were treated with exosomes collected from the supernatant of each liver cell groups. Both gene and protein expression of chondrocyte matrix degradation-synthetic markers MMP3, MMP13, SOX9, ADAMTS5 were detected.RESULTS 100 μg·mL^-1 was the optimal concentration of the decoction of Paeonia lactis. After hydrogen peroxide intervention, the gene and protein expression of cell senescence markers p16, p21 and p53 in the senescence group were all higher than those in the normal group (P < 0.05), but were lower in the Paeonia lactis group than those in the senescence group (P < 0.05). Exosomes collected by liver cells from each group presented a bistratal membranaceous structure, with no difference in morphology and size. The enrichment of the exosomes in particle sizes all met the range of 40-120 nm, the representative particle sizes were enriched at 116.8 nm, and the abundance was 98%. The exosome markers CD9, CD63, and CD81 were all positively expressed. The levels of pro-inflammatory cytokines TNF-α and IL-1β in chondrocytes supernatant increased after LPS stimulation compared with before (P < 0.01), and PHK67 staining reagent was used to confirm the uptake of chondrocyte exosomes in each group. The expression levels of genes and proteins of chondrocyte matrix degradation-synthetic markers MMP3, MMP13, SOX9 and ADAMTS5 in the senescence group were all higher than that in the normal group (P < 0.05), while the exosomes in the Paeonia lactis group were lower than that in the senescence group (P < 0.05).CONCLUSION Ageing phenotype hepatocyte exosomes can aggravate the LPS-induced degeneration of inflammatory chondrocytes, and the decoction of Paeonia lactiflora has a benign intervention in this process.

Effect of Changpu Yujin Decoction on Synaptosome SNARE Protein Complex in Tourette Syndrome Model Rats

FENG Peng, SUN Zhi-qian, LUO Wen-zhen, SHI Zheng-gang, LI Yu-xia, WU Li-ping, SHANG Jing, TIAN Wen-xia, CHEN Jing

2021, 37(5): 709-719. doi: 10.14148/j.issn.1672-0482.2021.0709

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OBJECTIVE To study the regulatory effect of Changpu Yujin Decoction on the SNARE protein complex in the synaptosomes of Tourette syndrome (TS) model rats, and to reveal the pharmacodynamic mechanism of Changpu Yujin Decoction in the treatment of TS.METHODS 240 SPF SD male rats (3 weeks) were randomly divided into blank group (n=60) and model group (n=180). Model group received intraperitoneal injection of 3, 3'-iminodipropionitrile to establish TS model. After the TS model was successfully established, the model rats were randomly divided into model group, tiapride group, and Changpu Yujin Decoction group, each with 60 rats. The intragastric administration was started from the next day after the TS model was made (d0). The blank group and the model group were given normal saline, and the other groups were given corresponding drugs, once a day, for 4 consecutive weeks. At d0, d7, d14, d21 and d28, 12 rats were randomly selected from each group. After anesthesia, the striatum was taken out, and the synaptosomes in the striatum were prepared by Percoll density gradient centrifugation. Morphological identification was performed under transmission electron microscope; The level of dopamine (DA) in the striatum was examined by ELISA; Expression of SNAP-25, Syntaxin-1a and VAMP-2 in the synaptosomes/striatumwere measured by qPCR, Western blot analysis and immunohistochemical staining.RESULTS Compared with the blank group, the DA content in the striatum in the model group was reduced (P < 0.01), and the expressions of SNAP-25, Syntaxin-1a, VAMP-2 mRNA and protein in the synaptosome/striatum significantly reduced (P < 0.05, P < 0.01); Compared with the model group, the DA content in striatum and the mRNA and protein expression levels of SNAP-25, Syntaxin-1a, VAMP-2 in the tiapride group and Changpu Yujin group showed a gradual increase trend during the intervention period (d7, d14, d21, d28); At d28 (after the end of treatment), the expressions of SNAP-25, Syntaxin-1a, VAMP-2 mRNA, Syntaxin-1a protein in synaptosome and SNAP-25 and VAMP-2 protein in the striatum were higher than those of tiapride group (P<0.05, P < 0.01).CONCLUSION Changpu Yujin Decoction promotes the release of DA by regulating the expression of SNAP-25, Syntaxin-1a, and VAMP-2, thereby exerting its anti-tic effect.

Analysis of Alkaloids in Aconiti Lateralis Radix Praeparata and Prediction of Their Mechanism in the Treatment of Cancer

LU Chao-ying, DING Meng-lei, CAI Shu-hui, XIE Hui, ZHANG Wen, DI Liu-qing

2021, 37(5): 720-729. doi: 10.14148/j.issn.1672-0482.2021.0720

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OBJECTIVE To quantify the alkaloids in aqueous extract of Aconiti Lateralis Radix Praeparata(Fuzi in Chinese) by ultra performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS), meanwhile investigate the anti-cancer mechanism of these alkaloids by network pharmacology. This article aimed to provide a reference for the material basis of anticancer effect of Fuzi.METHODS UPLC-MS/MS was used to analyze 12 alkaloids in Fuzi aqueous extract. The alkaloids and disease targets were predicted by Swiss Target Prediction and Gene Cards platform. The related function network was constructed by Cytoscape software. Finally, the key gene was analyzed by GO and KEGG pathway enrichment analysis.RESULTS Monoester alkaloids accounted for the highest proportion (59.07%), followed by alcohol amine alkaloids (29.48%). Network pharmacology speculated that MTAP (methylthioadenosine phosphorylase) and ABCB1 (ATP binding cassette subfamily B member 1) genes were the key targets for the anticancer efficacies of active alkaloids. The key targets were closely related to inflammatory response, phosphatidylinositol-mediated signaling, HIF-1 signaling pathway, estrogen signaling pathway and central carbon metabolism in cancer.CONCLUSION The developed method can determine 12 kinds of alkaloids in Fuzi simultaneously. The method is simple, feasible, accurate and reliable, which can provide the basis for clinical anticancer application and laid the foundation for further molecular biological research of Fuzi.

In Vitro Dissolution and Consistency Evaluation of Compound Danshen Tablets Based on RTCA Technology

ZHOU Yue, MA Xiao-fei, MA Li-xia, ZHANG Jia, ZHUANG Xin-ya, YU Yi-ting, ZHANG Qian, DONG Jie, CHEN Jun, YAN Guo-jun

2021, 37(5): 730-736. doi: 10.14148/j.issn.1672-0482.2021.0730

[Abstract](189) [FullText HTML] (48) [PDF 1916KB](69)

Abstract:
OBJECTIVE Based on real-time cell-based assay (RTCA), the feasibility of evaluating the in vitro dissolution of Compound Danshen Tablets by cell biological effect was investigated.METHODS According to the concentration gradient dependence of rat cardiomyocytes (H9C2) on the dissolution of Compound Danshen Tablets at different times, RTCA was used to monitor the dynamic changes of cells in different time. Thus, a dissolution kinetic model based on cell index (CI) was established. At the same time, the dissolution rate was calculated to evaluate the correlation and consistency with the dissolution curve determined by traditional UV spectrophotometry. Finally, DDSolver software was used for correlation analysis.RESULTS Taking the dissolution curve obtained by UV spectrophotometry as a reference, the difference factor f₁ of the dissolution curve of Compound Danshen Tablets from three different manufacturers was less than 15, and the similarity factor f₂ was greater than 50. Under the two evaluation methods, the best fitting model of dissolution curves of Compound Danshen Tablets from the same manufacturer were consistent.CONCLUSION This result showed that the cell biological effect evaluation method based on RTCA could basically reflect the characteristics of in vitro dissolution of Compound Danshen Tablets. The dissolution evaluation method based on the cell index is expected to become a new detection method for the in vitro dissolution of solid preparations of traditional Chinese medicine.

Potential Mechanism of Platycodon Grandiflorum in the Prevention of Acute Lung Injury Based on Non-Target Serum Metabolomics

ZHOU Yang, XIE Tong, SHI Chen, KANG An, DENG Hai-shan, SHAN Jin-jun

2021, 37(5): 737-743. doi: 10.14148/j.issn.1672-0482.2021.0737

[Abstract](272) [FullText HTML] (70) [PDF 4656KB](88)

Abstract:
OBJECTIVE To investigate the potential mechanism of platycodon grandiflorum in preventing acute lung injury in mice based on non-target serum metabolomics.METHODS Twenty-four C57BL/6J mice were randomly divided into control, model, positive and platycodon grandiflorum groups. After 7 days of drug intervention, except for the control group, the other mice were injected with lipopolysaccharide (3 mg·kg^-1) to establish the acute lung injury model and the lung pathology and the expression of inflammatory factors in each group were determined. The serum of mice was collected, and the serum samples were detected by mass spectrometry using GC-MS. The serum metabolic profiles were compared by PCA and Metaboanalyst 5.0 was used to analyze related metabolic pathways.RESULTS Compared with the control group, the lung pathology of the model group was serious, and the inflammatory factors significantly increased (P < 0.05). Compared with the model group, the pathological conditions of the positive and platycodon grandiflorum groups were improved to some extent, and the inflammatory factors were significantly reduced (P < 0.01). Serum metabolomics results showed that the metabolic profile of the control group and the model group was significantly different, and the metabolic profiles of the positive and platycodon grandiflorum group were close to the normal group.CONCLUSION Platycodon grandiflorum can improve the inflammation in acute lung injury mice, its potential mechanism may be related to the callback variety of the content of serum metabolites and control multiple metabolic pathways.

UPLC-ESI-Q-TOF-MS Analysis of Xanthones in Swertia Chirayita

DONG Hui-min, XU Ru-ling, CHEN Xiao-qing, YANG Fu-yan, FAN Jun-ting, JU Jian-ming

2021, 37(5): 744-749. doi: 10.14148/j.issn.1672-0482.2021.0744

[Abstract](286) [FullText HTML] (100) [PDF 1759KB](91)

Abstract:
OBJECTIVE To establish a qualitative analysis method of xanthones in Swertia chirayita by ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS).METHODS Acquity HSS T₃ column (100 mm×2.1 mm, 1.8 μm) was used as the chromatographic column, with 0.1% formic acid in water-0.1% formic acid in acetonitrile as the mobile phase for gradient elution.The volume flow rate was 0.4 mL·min^-1 and the column temperature was 40 ℃.In the positive and negative ion modes, the mass spectrum data of Swertia chirayita was collected and identified by Masslynx4.1 software combined with SciFinder database, comparison with mass spectrometry data analysis, reference materials and reference to relevant literatures.RESULTS A total of 25 xanthone compounds were identified, 3 of which were first discovered including 7-O-β-D-xylopyranosyl-1, 8-dihydroxy-3-methoxyxanthone, swerpunilactone B and 8-O-[β-D-xylopyranose(1→6)-β-D-glucopyranose]-1, 7-dihydroxy-3-methoxyxanthone.CONCLUSION The method can provide an experimental basis for the qualitative analysis of xanthones and the quality control of medicinal materials in Swertia chirayita.

Effects of Prenylated Compounds Derived from Psoralea Corylifolia against Human CYP1A1 and Corresponding Molecular Docking Validation

QIN Zi-fei, WANG Pei-le, XING Han, HAN Li, BIAN Hua, YANG Jing, ZHANG Xiao-jian

2021, 37(5): 750-159. doi: 10.14148/j.issn.1672-0482.2021.0750

[Abstract](213) [FullText HTML] (40) [PDF 5044KB](98)

Abstract:
OBJECTIVE To investigate the effects of prenylated compounds derived from Psoralea corylifolia against human CYP1A1, and validate the obtained results by molecular docking.METHODS 7-Ethoxyresorufin was used as the probe substrate for human CYP1A1. In addition, the ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-TQD-MS) conditions for resorufin (the specific metabolite of 7-ethoxyresorufin by CYP1A1) were optimized. Based on the optimized condition, 7-ethoxyresorufin was incubated with CYP1A1 in the absence (control) and presence of bavachin, psoralidin, isobavachalcone, isobavachin and bavachinin at different concentration (1, 10, 100 μmol·L^-1), respectively. Three kinetic models were applied to calculate the K_ivalues by nonlinear regression for competitive inhibition, noncompetitive inhibition, and mixed-type inhibition, respectively. The molecular docking between prenylated compounds and CYP1A1 was performed by Autodock 4.2.RESULTS These findings demonstrated that bavachin, psoralidin, isobavachalcone, isobavachin and bavachinin exhibited potent inhibitory effects against CYP1A1, and the corresponding IC₅₀values were 0.28, 0.49, 0.36, 2.24, 4.07 μmol·L^-1, respectively. Based on the smallest Akaike information criterion (AIC) and Schwarz criterion (SC) principles, bavachin and isobavachalcone exerted competitive inhibition against CYP1A1 with K_i values of 0.12 and 0.23 μmol·L^-1, respectively, while psoralidin displayed noncompetitive inhibitory effects against CYP1A1(K_i=0.59 μmol·L^-1). Molecular docking results indicated that hydrogen bond, π-π bond and hydrophobic interaction could be formed between bavachin (or isobavachalcone) and CYP1A1 protein crystals, and their binding free energies were -10.145 and -8.286 kcal·mol^-1(1 kcal=4.2 kJ), respectively. This might be the reason why these compounds have strong affinity with CYP1A1, and thus produce strong inhibitory activity.CONCLUSION Prenylated compounds in Psoralea corylifolia are identified as potent inhibitors for CYP1A1 (IC₅₀ < 5 μmol·L^-1). When dehydration reaction occurrs in bonds 1 and 2, the inhibitory effects of herbal compounds against CYP1A1 increases. Herbal compounds with isopentene group at C-6 position exhibits stronger inhibitory effects against CYP1A1 than those with isopentene group at C-8 position. Herbal compounds with C-7-OCH₃ displays weaker inhibitory effects against CYP1A1 than those with C-7-OH. The molecular docking results also validates the presence of strong affinity between bavachin (or isobavachalcone) and CYP1A1 protein.

Comparative Study on the Medication Characteristics of Well-Known Veteran Traditional Chinese Medicine Doctors in the Treatment of Lung Cancer Based on Complex Networks Algorithm

SHEN Gang-lei, JIN Chun-hui, NI Yi-qun, YANG Tao, XIE Jia-dong, HU Kong-fa

2021, 37(5): 760-764. doi: 10.14148/j.issn.1672-0482.2021.0760

[Abstract](209) [FullText HTML] (47) [PDF 1287KB](89)

Abstract:
OBJECTIVE To compare the characteristics of medication based on syndrome differentiation in the treatment of lung cancer between Professor Zhou Zhongying (Professor Zhou) and Professor Zhao Jingfang (Professor Zhao) by complex network algorithm, and to provide a new research idea and data for summarizing and inheriting the clinical experience of well-known veteran traditional Chinese medicine (TCM) doctors. METHODS The lung cancer outpatient electronic medical records diagnosed by Professor Zhou and Professor Zhao were collected, and the complex network algorithm was applied to construct "syndrome-syndrome" and "syndrome-medication" complex network maps based on the two doctors' medical records, so as to analyze the individualized differences between their experience in medication based on syndrome differentiation of lung cancer. RESULTS Through the analysis of the complex network map, it was found that the syndromes of lung cancer identified by the two doctors both included deficiency of qi and yin. As for the differences, Professor Zhou identified syndromes as phlegm stagnation and lung constraint, heat toxin and phlegm stagnation, spreading of cancerous toxin, as well as binding of phlegm and stasis, while Professor Zhao identified syndromes as deficiency of lung and spleen qi, phlegm-heat accumulation in lung, spleen deficiency and phlegm dampness, along with liver constraint and spleen deficiency. The medications commonly used by Professor Zhou in treating lung cancer included Glehniae Radix, Adenophorae Radix, Ophiopogonis Radix, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Herba Euphorbiae Helioscopiae, Pseudostellariae Radix, Agrimoniae Herba, Ranunculi Ternati Radix, Hedyotis diffusa Willd, and processed Bombyx Batryticatus, while Professor Zhao commonly used Codonopsis Radix, stir-fried Atractylodis Macrocephalae Rhizoma, processed Pinelliae Rhizoma, Poria, Pseudostellariae Radix, Adenophorae Radix, Glehniae Radix, Citri Reticulatae Pericarpium, Coicis Semen, Polyporus, Setariae Fructus Germinatus, Hordei Fructus Germinatus, and honeyed Eriobotryae Folium. CONCLUSION Treatment of lung cancer from Professor Zhou is based on the cancerous toxin theory, and he emphasizes treatment based on syndrome differentiation of cancerous toxin, while treatment of lung cancer from Professor Zhao is based on the theory of maintaining balance with the moderate regulation, and her main treatment method is banking up earth to generate metal.

Analysis of Masters of Traditional Chinese Medicine Zhou Zhongying's Experience in Treating Tumors by Compounding Formulae from Syndrome Differentiation Based on Pathomechanism

LI Liu, CHENG Hai-bo, YE Fang, WU Mian-hua

2021, 37(5): 765-168. doi: 10.14148/j.issn.1672-0482.2021.0765

[Abstract](212) [FullText HTML] (34) [PDF 1147KB](120)

Abstract:
Professor Zhou Zhongying, a master of traditional Chinese medicine, advocated a new system of syndrome differentiation and treatment based on pathomechanism in Chinese medicine. He proposed that the basic characteristics of the pathomechanism of the complicated disease were their complexities, and pointed out that compound prescriptions was the basic strategy for the treatment of those diseases such as tumors. Closely revolving around the subject of syndrome differentiation based on pathomechanism, the study summarizes Zhou Zhongying's experience in the prescribing and applying formulae for malignant tumors from three aspects including the theoretical basis of compound prescriptions, the basic ideas of compound prescriptions, as well as the similarities and differences of compound prescriptions for different tumors, to further expand the ideas of prescribing and applying formulae along with clinical diagnosing and treating of complicated diseases such as tumors.

Characteristics of the Differentiation and Treatment of Kidney-Related Syndromes and Diseases According to Zhang Jianzhai

KONG wei, ZHU Cheng-ying, NI Bin, WANG Gang, ZOU Yan-qin

2021, 37(5): 769-770. doi: 10.14148/j.issn.1672-0482.2021.0769

[Abstract](197) [FullText HTML] (59) [PDF 1117KB](119)

Abstract:
Taking the cases of edema and strangury in the Single-copy Edition of Zhang Jianzhai's Case Records Handwritten by Zou Yunxiang as representative, this study analyzes the characteristics of the differentiation and treatment of kidney-related syndromes and diseases according to Zhang Jianzhai. In the differentiation and treatment of edema, Zhang Jianzhai often used the treatment methods of evacuating and inducing sweating, conducting and promoting urination, as well as unblocking yang and transforming qi. As for the differentiation and treatment of strangury, the treatment of curing kidney was often combined with treatments of strengthening the spleen and regulating the lung, supplementing the center and boosting qi, or evacuating and directing counterflow downward. In addition, the medicine was also often applied flexibly combined with decocting while wrapping pills and powder to form a decoction.

Characteristics of the Differentiation and Treatment of Lung-Related Syndromes and Diseases According to Zhang Jianzhai

LI Wei-ting, ZENG An-ping, WANG Gang, ZOU Yan-qin

2021, 37(5): 771-774. doi: 10.14148/j.issn.1672-0482.2021.0771

[Abstract](194) [FullText HTML] (56) [PDF 1143KB](92)

Abstract:
This study introduces the characteristics of the differentiation and treatment of lung-related syndromes and diseases according to Zhang Jianzhai, a famous doctor in the Republic of China. Besides, we select three diseases including cough, asthma, and lung consumption as representatives and discuss them separately. Regarding cough, Zhang Jianzhai's common treatment methods include diffusing and rectifying the lung with acrid medicine, purifying the lung and directing counterflow downward, fortifying the spleen, and dissolving phlegm, as well as boosting qi to eliminate pathogens. As for asthma, doctors should first differentiate whether the syndromes are newly contracted or formerly contracted, deficient or excess, and then treat the diseases with main methods of diffusing and purifying the lung along with receiving and containing qi. For lung consumption, doctors should identify the differences and similarities between the disease body and the deficient root based on regulating and nourishing treatment, emphasize transmission and change relationships between viscera, and take into account the loss of qi, blood, yin, and yang. In conclusion, Zhang Jianzhai's treatment of lung-related diseases is based on a variety of therapeutic methods including boosting qi to eliminate pathogens, regulating and nourishing, purifying and rectifying the lung, applying acrid medicine to diffuse the lung, as well as nourishing yin and suppressing the excessive yang. In addition, his treatments are characterized by applying light medicines without hurting the healthy qi.

Characteristics of Gynecological Syndromes Differentiation and Treatment According to Zhang Jianzai

ZHAO Guo-chen, ZENG An-ping, GUO Xiao-juan, WANG Gang, ZOU Yan-qin

2021, 37(5): 775-777. doi: 10.14148/j.issn.1672-0482.2021.0775

[Abstract](159) [FullText HTML] (63) [PDF 1126KB](105)

Abstract:
Zhang Jianzhai's treatment of gynecological diseases is characterized by: Identifying the deficiency and excess together with harmonizing qi and blood in both supplementing and dredging way, benefiting the liver and kidney combined with consolidating the chong and ren mai to regulate and nourish extraordinary vessels, reinforcing the five viscera conjoined with differentiating cold and heat to treat both the exterior and interior. In addition, Zhang Jianzhai pays special attention to the syndrome differentiation of qi and blood, takes into account the aspects of cold and heat, exterior and interior, deficiency and excess, as well as zang-fu organs. His treatment is good at regulating and nourishing extraordinary vessels, applying both tough and gentle therapies, as well as eliminating the excess with light medicine.

Research Progress on Metallic Mineral Chinese Medicines

XU Shan, XU Liu, XIANG Tang-yong, ZHU Ling, GU Yi, CAI Bao-chang, CHEN Zhi-peng

2021, 37(5): 778-785. doi: 10.14148/j.issn.1672-0482.2021.0778

[Abstract](372) [FullText HTML] (453) [PDF 1220KB](158)

Abstract:
As characteristic components of traditional Chinese medicine, the application of metal mineral Chinese medicine has a history of thousand years. This article summarizes the research on the components, flavor and meridian tropism, clinical application, pharmacological research, and processing of metal mineral medicines, aiming to provide references for its further development and utilization, inquiry of material basis and mechanism of action research.

Present Situation and Developing Trend on Drying of Chinese Herbs

JU Hao-yu, ZHAO Shi-hao, ZHAO Hai-yan, ZHANG Wei-peng, GAO Zhen-jiang, XIAO Hong-wei

2021, 37(5): 786-196. doi: 10.14148/j.issn.1672-0482.2021.0786

[Abstract](928) [FullText HTML] (86) [PDF 1404KB](193)

Abstract:
Drying is a key process which affects the quality and efficacy of Chinese herbal medicine. The product usage and economic value are directly influenced by the drying results. In this paper, the drying technology, drying models and the effective constituent degradation regulation of Chinese herbals were reviewed. As to drying technology, the advantages and disadvantages as well as adaptive of traditional drying methods including shading drying, sun drying and hot air drying and modernly drying methods containing air implement drying, vacuum pulsed drying, medium short-wave infrared drying, and radio-frequency drying were analyzed in detail. In drying model section, the application of theoretical model, semi-theoretical model and empirical model were illustrated. Taking alkaloids, flavonoids, polysaccharides and pigments as the representative indexes of Chinese herbal medicine, the degradation influencing factors and changing regulation were discussed. It is necessary to understand the drying characteristic of the different Chinese herbs drying technology and the degradation regulation of the medicinal component and to establish a suitable drying model, which can provide a theoretical foundation different types of Chinese herbal medicine to choose appropriate drying technology and process.

2021 Vol. 37, No. 5

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