南京中医药大学学报

Discussion on Waxing and Waning Rules of Essence-Yin and Essence-Yang in Menstrual Cycle Rhythm and Its Diagnosis and Treatment

XIA Gui-cheng, TAN Yong

2021, 37(3): 321-324. doi: 10.14148/j.issn.1672-0482.2021.0321

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Abstract:
The paper discussed the waxing and waning of essence-yin and essence-yang rules in menstrual cycle rhythm and the treatment thought of related diseases. Based on the theory of Yi, Professor Xia Guicheng proposed the concept of essence-yin and essence-yang in the female reproductive physiological system, which elaborated its material basis, zang-fu regulation and its function on the rehabilitation of menstrual cycle. Combined with the further analysis of gynecological diseases, Professor Xia Guicheng considered that the menstrual cycle rhythm was equal to the change rule of the female reproductive physiological system, the treatment thought should base on the modern disease spectrum to extend the application of traditional Chinese medicine theories in gynecology.

New Insight and New Methodology for Herb-Drug Interactions Based on Cellular Pharmacokinetics

LIU Dan-chen, ZHOU Fang, ZHANG Jing-wei, WANG Guang-ji

2021, 37(3): 325-330. doi: 10.14148/j.issn.1672-0482.2021.0325

[Abstract](229) [FullText HTML] (287) [PDF 1854KB](199)

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Herb and drug combination has become a common phenomenon on the clinical treatment, but its judgement criteria lacks a complete scientific basis. Traditional pharmacokinetic studies, restricted to plasma drug concentration, cannot clarify drug metabolism and disposition process in the target site, creating limitations such as irrelevant relationship between plasma PK and PD. In recent years, more and more studies focus on quantitative analysis of the process of drugs into the target area and cells through blood, which promotes pharmacokinetic researches from "macro" plasma into "micro" cells. Therefore, this paper mainly summarizes new technologies, new methods of herb-drug interaction researches based on the thought of cellular pharmacokinetics, as well as studies and clinical applications of herb-drug combination to improve effect and decrease toxicity.

Artificial Intelligence-Biology: An Important Strategic Resource and Competitive Hot Spot in the Future Research of TCM Modernization

LU Yin, WEI Zhong-hong, ZOU Wei, SONG Meng-yao

2021, 37(3): 331-336. doi: 10.14148/j.issn.1672-0482.2021.0331

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The modernization of traditional Chinese medicine (TCM) has made some achievements in the past two decades, but there are still many obstacles. With the application of artificial intelligence(AI)technology in the field of Biological Science (including protein structure analysis, new drug development, etc.), it may bring new research ideas and strategies for the breakthrough of obstacles restricting the modernization of TCM. The continuous accumulation of clinical and research data of TCM also provides the basis for the integration of AI and TCM. This article analyzes the hotspot and forward of AI in the field of TCM, then further investigates the enormous impetus of AI technology in the research of key scientific issues of TCM, such as the inheritance and innovation of academic ideas of TCM masters, the modern biological basis of TCM therapeutic principle, the material basis and mechanism of action of TCM. Those may be the strategic resource and competition point for the modernization of TCM in the future.

Research Progresses on Target Identification of Natural Products by Chemoproteomics

CHEN Xiu-zhen, YAN Xin-yu, YU Cheng-li, ZHANG Yi-nan

2021, 37(3): 337-347. doi: 10.14148/j.issn.1672-0482.2021.0337

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Finding new natural product-based drugs from the resources of traditional Chinese medical herbs can rapidly promote the modernization of traditional Chinese medicine. The bottleneck in the development of natural product based-drugs is their unknown protein targets and unclear mechanisms of action. Recently, a growing number of methods for the target identification of medicinal compounds have emerged, in relation to explicitly reveal their pharmacological mechanisms and toxic side effects. Particularly, mass-based chemoproteomic methods for the target identification, which can be applied with complicated biological models, has the advantages of high reproducibility and high accuracy in indiscriminately determining the protein targets. Since it becomes the most important tool in the discovery of natural product targets, herein we would like to provide a holistic perspective of these chemoproteomic methods, including their principles, pros and cons, the range of application, and representative examples.

Discuss on the Pathogenesis of Colorectal Precancerous from the Perspective of Traditional Chinese Medicine

WEI Xiao-man, LI Liu, CHENG Hai-bo

2021, 37(3): 348-351. doi: 10.14148/j.issn.1672-0482.2021.0348

[Abstract](282) [FullText HTML] (104) [PDF 1150KB](171)

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Under the guidance of the theory of cancerous toxin pathogenesis, it is proposed that the common pathogenesis of colorectal precancerous lesion is damp-heat toxin accumulation and deficiency of spleen qi. Damp-heat toxin is induced by deficiency of spleen, retained in zang-fu organs and then transformed into cancerous toxin. Deficiency of spleen is the fundamental pathogenesis of colorectal pre-cancer lesion while damp-heat toxin accumulation is the development condition. The endogenous cancerous toxin is the key to cancerization. Combined with endoscopic pathological grading, the evolution of pre-colorectal lesion can be divided into cancerous toxin-free period and cancerous toxin period according to whether there is endogenous cancerous toxin or not. The process of disease onset induced by cancerous toxin is the process of colorectal precancerous lesion transforming into colorectal cancer. Therefore, according to the pathogenesis of colorectal precancerous lesion either in cancerous toxin-free period and cancerous toxin period, corresponding treatment methods should be applied to remove the source of cancerous toxin or endogenous cancerous toxin, which can achieve the purpose of inhibiting cancerization and reversing the formation of cancer.

Comparison of the Similarities and Differences between Tang Zonghai's and Zhang Xichun's Ideas on the Treatment of Hematemesis

XU Xin-yu, LI Ping, YUAN Qi, ZHAO Song-ting, YAO Meng-xi, LI Feng

2021, 37(3): 352-355. doi: 10.14148/j.issn.1672-0482.2021.0352

[Abstract](270) [FullText HTML] (51) [PDF 1156KB](147)

Abstract:
The paper compares the similarities and differences between Tang Zonghai's and Zhang Xichun's ideas on the treatment of hematemesis. Both of them attribute the cause of hematemesis to the adverse rising of qi and fire-heat, and the priority of treatment method is lowering the stomach qi to stop bleeding and should focus on eliminating blood stasis. However, Tang Zonghai (Tang) advocates eliminating blood stasis after stopping bleeding, while Zhang Xichun (Zhang) uses methods of eliminating blood stasis in the process of stopping bleeding. Besides, as to acute bleeding, Tang prescribes Dushen Decoction, while Zhang copes it with Daizheshi (haematitum) in addition to Dushen Decoction. Moreover, Tang establishes the method of soothing and tonifying blood, while Zhang makes good use of haematitum to treat sequela arising from blooding. It proposes that the exposition of Zhang enriches the content of Tang's four methods of treating blood patterns and can be a reference to modern clinical practice.

The Effect of Yinjia Pellet on the Short Term Efficacy and Long Term Recurrence Rate of Treating Graves' Hyperthyroidism

SUN Xin-yi, MIAO Jun-jun, GE Jin

2021, 37(3): 356-359. doi: 10.14148/j.issn.1672-0482.2021.0356

[Abstract](331) [FullText HTML] (54) [PDF 1162KB](115)

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OBJECTIVE To discuss the effect of Yinjia pellet on the short term efficacy and long term recurrence rate of treating hyperthyroidism in diffuse goiter (Graves' disease).METHODS 80 patients with Graves' disease and hyperthyroidism in Jiangsu Hospital of traditional Chinese medicine were randomly divided into two groups by SAS system. The treatment group was given Yinjia pellet combined with western medicine while the control group was only given western medicine. After six-month course, the short term efficacy was observed. We followed up the patients for two years after the treatment and estimated the recurrence rate.RESULTS After treatment, the degree of proptosis and traditional Chinese medicine syndrome scores in the two groups were improved (P < 0.01), and the treatment group was better than the control group (P < 0.05, P < 0.01). The levels of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyrotrophin receptor antibody (TRAb) were improved (P < 0.05, P < 0.01), which in the treatment group were better than those in the control group (P < 0.05, P < 0.01) and took less time to recover than those in the control group (P < 0.01). The total efficacy rate in the treatment group was higher than that of the control group (P < 0.01). With the two-year follow-up, it was found that the recurrence rate in the treatment group was lower than that in the control group (P < 0.05).CONCLUSION Yinjia pellet combined with Western medicine has more significant effect on treating hyperthyroidism of Graves' disease, which can reduce the recovery duration of thyroid function and the recurrence rate of hyperthyroidism.

The Effect of Zhihuang Zhitong Powder on Acute Ankle Sprain and Morphology of Injured Ligament

QI Xiu-chun, SUN Nan, GUO Xi-qin, HAN Chong-tao, CHEN Xin, CHENG Shuai-bang

2021, 37(3): 360-365. doi: 10.14148/j.issn.1672-0482.2021.0360

[Abstract](240) [FullText HTML] (40) [PDF 1495KB](136)

Abstract:
OBJECTIVE To discuss the effect of Zhihuang Zhitong Powder on acute ankle sprain and morphology of injured ligament.METHODS The 92 patients with acute ankle sprain were randomly divided into the control group and the observation group, 46 cases each. The control group was given the basic therapy combined with Diclofenac Diethylamine Emulgel while the observation group was given the basic therapy combined with Zhihuang Zhitong Powder. The course lasted 14 days. The efficacy of the two groups were compared after treatment in terms of those indexes, including the pain score of visual analogue scale (VAS), the level of serum oxidative stress factors, the ankle circumcision, the ankle flexion, the activity of back extension, the thickness of damaged ligament and the changes in ankle function. The period of pain relief and swollen joint recovery along with adverse skin reactions in the two groups were recorded.RESULTS After treatment, the pain score of VAS, the thickness of the anterior cruciate ligament and the anterior cruciate ligament, the ankle circumcision, scores of the ankle flexion, the activity of back extension, as well as the ankle and hind foot function evaluation table were significantly improved(P < 0.05). The activity of superoxide dismutase (SOD) was higher than before treatment (P < 0.05). The level of alondialdehyde (MDA), fibroblast growth factor (FGF)-2, conversion growth factor (TGF)-β1, matrix metalloproteinases (MMP)-9 and interleukin-1β (IL-1β) were lower than those of the same group before treatment. the observation group was higher than that in the control group (P < 0.05). The total efficiency of the observation group was better than that of the control group (P < 0.05). The period of pain relief and swollen joint recovery in the observation group were shorter than those of the control group (P < 0.05). There was no statistical difference in the incidence of adverse skin reactions in the two groups (P>0.05).CONCLUSION The effect of Zhihuang Zhitong Powder in the treatment of acute ankle sprain was better than that of Diclofenac Diethylamine Emulgel, which can enhance antioxidant activity, inhibit oxidative stress response, improve lateral ligament morphology, and promote the recovery of ankle function.

Clinical Study on Self-Made Fuzheng Jiedu Formula in Treating Cancer-Related Fatigue of Patients with Gastric Cancer after Chemotherapy

LI Ye, YANG Ru-yi, LI Meng-qi, ZHANG Wen-jing, CHEN Fa-zhang

2021, 37(3): 366-370. doi: 10.14148/j.issn.1672-0482.2021.0366

[Abstract](303) [FullText HTML] (77) [PDF 1175KB](135)

Abstract:
OBJECTIVE To observe the effect of self-made Fuzheng Jiedu Formula on cancer-related fatigue (CRF) of patients with gastric cancer after chemotherapy.METHODS 110 gastric cancer patients with cancer-related fatigue were randomly divided into the treatment group and the control group with 55 cases in each group. The treatment group was given self-made Fuzheng Jiedu Formula. The control group was given Zhenqi Fuzheng Capsule. The scores of Cancer Fatigue Scale(CFS)and Brief Fatigue Inventory(BFI)in both two groups before and after treatment were evaluated. The changes of T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺), tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA-199) and carbohydrate antigen 724 (CA-724) were detected.RESULTS After treatment, there was no difference in cognitive scores between the two groups (P>0.05). The scores of physical, emotional, total and BFI were decreased, which in the treatment group were better than those in the control group (P < 0.05, P < 0.01). The levels of CD3⁺, CD4⁺ and CD4⁺/CD8⁺ in the two groups were increased, and the levels of CD8⁺were decreased, which in the treatment group were betterer than those in the control group (P < 0.05). The levels of CEA, CA-199 and CA-724 in the treatment group were decreased (P < 0.05, P < 0.01), which were better than those in the control group (P < 0.05, P < 0.01).CONCLUSION Self-made Fuzheng Jiedu Formula can significantly improve the immune function of patients, reduce the level of tumor markers, and relieve the degree of CRF in patients with gastric cancer.

Clinical Efficacy and Mechanism of Wumei Pill in the Treatment of Chemotherapy-induced Intestinal Mucositis

LU Dong-xue, YAN Jing, SUN Zhi-guang, LI Xuan, LIU Feng, WANG Ya-jun, GE Fei

2021, 37(3): 371-375. doi: 10.14148/j.issn.1672-0482.2021.0371

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OBJECTIVE To observe the effect of Wumei pill on diarrhea in chemotherapy-induced intestinal mucositis (CIM) and its possible mechanism of action.METHODS We selected 50 CIM outpatients with diarrhea in Hai'an TCM Hospital, and divided them into the treatment group with 25 cases and the control group with 25 cases in accordance with the random number table. In the control group, oral loperamide was administered, while as for the treatment group, Chinese herbal decoction Wumei pill was given. The total course of treatment was four weeks. The incidence rate of diarrhea and the total effective rate of the patients were observed, and the scores of traditional Chinese medicine (TCM) syndrome were evaluated. In addition, we measured serum inflammatory factors and After treatment, the incidence rate of diarrhea and the scores of TCM syndrome were decreased in both groups (P < 0.05, P < 0.01), and results in the treatment group were better than those in the control group (P < 0.01). The clinical efficacy rate of the treatment group was higher than that of the control group (P < 0.05). The levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), endothelin (ET) and D-lactate were decreased (P < 0.05, P < 0.01), while the levels of interleukin 10 (IL10) were increased (P < 0.01). The abundances of enteropathogenic bacteria were reduced while the abundances of probiotics were increased (P < 0.05, P < 0.01), and the treatment group were better than the control group (P < 0.01).CONCLUSION Wumei pill can significantly improve the symptoms associated with diarrhea of CIM, and the mechanism may be related to the anti-inflammatory response, improvement of intestinal mucosal barrier function and regulation of intestinal flora under the multi-target effect of the Chinese herbal compound.

Honokiol Loaded Mixed Micelles Fororal Delivery Using Novel F127 and TPGS as Carriers

CHEN Xiao-qing, DING Ping-gang, XU Ru-ling, DONG Hui-min, QI Zhi-chao, JU Jian-ming

2021, 37(3): 376-382. doi: 10.14148/j.issn.1672-0482.2021.0376

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OBJECTIVE The purpose of this research was to develop a self-assembled micelle using biocompatible copolymers Pluronic F127 (F127) and Vitamin E d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) to enhance the oral bioavailability and anti-cancer efficiency of honokiol (HK). METHODS The optimized prescription honokiol micelle (HK-M) was prepared by an ethanol solvent evaporation method. HK-M was characterized by transmission electron microscopy(TEM) and HPLC. The dialysis bag method was used to assesse the cumulative amount of HK released from the HK-M. Caco-2 cells were applied to measure the permeability of HK-M. The bioavailability and in vivo anti-tumor effect were also evaluated. RESULTS At the ratio of 4∶1 (F127∶TPGS), the HK-M was transparent and colourless with a small size (23.28 ± 2.01)nm and a spherical shape. The apparent solubility of HK in HK-M was dramatically increased to 4.76 mg/mL, suggesting that HK-M had good stability. Furthermore, encapsulation in micelles led to a sustained release of HK. HK-M enhances HK's permeability across Caco-2 cell monolayer. Compared with free HK, there was a 1.17-fold increase in the relative oral bioavailability for HK-M. Moreover, HK-M achieved a higher inhibition rate on tumor volume (35.17%) than HK group (14.86%). CONCLUSION

Astragaloside Ⅳ Regulates Blood Lipid and Inflammatory Factors Through NLRP3 Inflammasome in Early Diabetic Atherosclerosis Rats

GE Fan, WANG Wen-kai, ZHU Jing-tian, LI Zi-hang, SUN Yue, XUE Mei

2021, 37(3): 383-387. doi: 10.14148/j.issn.1672-0482.2021.0383

[Abstract](233) [FullText HTML] (51) [PDF 1681KB](111)

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OBJECTIVE To investigate the effect and mechanism of astragaloside Ⅳ in regulating blood lipid and inflammatory factors in early diabetic atherosclerosis rats.METHODS Forty-eight GK rats were randomly divided into model group, positive drugs (gliquantel positive drug combined with benazepril hydrochloride tablets) group, astragaloside Ⅳ low-dose and high-dose groups, 12 rats in each group were fed with high-fat diet. 12 Wistar rats were used as blank control. The administration groups were intragastrically administrated Gliquanone tablets (10 mg/kg), combined with Benazepril hydrochloride tablets (10 mg/kg), astragaloside Ⅳ (20, 40 mg/kg), respectively. The control group and model group were intragastrically given normal saline once a day for 6 weeks. The rat body weight and blood sugar were monitored. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) in serum of rats were determined by biochemical method. The pathological morphology of abdominal aorta of rats was observed by HE staining. The contents of IL-6, IL-10, CRP and TNF-α in rat abdominal aorta were determined by ELISA. The protein expression levels of NLRP3, ASC and Caspase-1 in rat abdominal aorta were detected by Western blot.RESULTS Compared with model group, astragaloside Ⅳ high and low dose groups significantly improved atherosclerosis, decreased blood glucose, levels of serum TC, TG, LDL, increased HDL level, decreased the levels of IL-6, CRP, TNF-α in abdominal aorta, increased IL-10 level, and down-regulated the protein expressions of NLRP3, ASC and Caspase-1 (P < 0.05, P < 0.01, P < 0.001, P < 0.000 1).CONCLUSION Astragaloside Ⅳ can regulate blood lipid and inflammatory status in early diabetic atherosclerosis rats, and the mechanism is closely related to the regulation of NLRP3 inflammasome related protein expression.

Effect of Fuzi Lizhong Pill on Intestinal Flora of Spleen Yang Deficiency IBS-D Rats Based on High-Throughput Sequencing Technique

LIN Xia, HUANG You, YANG Sha-sha, WEI Xin-yi, FU Chao-mei, LI Ru, ZHANG Zhen

2021, 37(3): 388-395. doi: 10.14148/j.issn.1672-0482.2021.0388

[Abstract](327) [FullText HTML] (65) [PDF 1762KB](157)

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OBJECTIVE To research the effect and mechanism of Fuzi Lizhong Pill (FLZP) on intestinal flora of spleen Yang deficiency IBS-D rats, and to explore the relationship between intestinal flora and spleen Yang deficiency in rats. METHODS 60 male SD rats were selected and randomly divided into normal group, model group, FLZP low dose group and FLZP high dose group. Rats in normal group were fed normally. The spleen Yang deficiency IBS-D model were established by using the combined factor modeling method of "irregular diet + tired excessive + senna lavage" for 21 days. After successful modeling, FLZP was administrated in rats of FLZP low and high dose groups for 21 days. Then feces samples were collected from rats. Total DNA was extracted from these feces samples. Primers were designed according to the V3-V4 region of bacterial 16S rRNA for amplification. Finally, Illumina Miseq platform was used for high-throughput sequencing. RESULTS Compared with normal group, the relative abundance of Bacteroidetes, Bacteroidia and Muribaculaceae in model group significantly reduced (P < 0.05) and the relative abundance of Clostridiaceae, Clostridium_sensu_stricto_1, Turicibacter, Blautia and Lactobacillus in model group significantly increased (P < 0.01). Compared with model group, the relative abundance of Bacteroidetes, Bacteroidia and Muribaculaceae in FLZP low and high dose groups significantly increased (P < 0.05) and the relative abundance of Clostridiaceae, Clostridium_sensu_stricto_1, Turicibacter, Blautia in FLZP low and high dose groups significantly reduced (P < 0.01). The relative abundance of Lactobacillus increased in FLZP low and high dose groups, and significantly in FLZP high dose group (P < 0.05). CONCLUSION FLZP can increase the relative abundance of probiotics Lactobacillus and recover the relative abundance of Bacteroidetes, Turicibacter and Blautia. The regulation of intestinal flora that is closely related to inflammation and immune system, is the important mechanism of FLZP in treating spleen Yang deficiency IBS-D diarrhea.

Research on the Therapeutic Mechanism of Sargentgloryvine Stem on CIA Rats Based on NF-κB/NLRP3 Pathway

YU Yun, YU Hui, FENG Jing, SHEN Fei, YU Bin, CHEN Qing, SHI Le, BIAN Yong

2021, 37(3): 396-399. doi: 10.14148/j.issn.1672-0482.2021.0396

[Abstract](289) [FullText HTML] (95) [PDF 1501KB](145)

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OBJECTIVE To investigate the symptom improvement and mechanism of sargentgloryvine stem on collagen-induced arthritis (CIA) in rats. METHODS The CIA model in rats was established, and the body weight, joint swelling degree and arthritis index were observed continuously. The levels of TNF-α, IL-1β, IL-6 and IL-18 in serum were detected by ELISA. The expressions of RANKL, p-IκB-α, NF-κB/p65, p-NF-κB/p65, NLRP3 and Caspase-1 in synovial joint of rats were detected by Western blot. RESULTS The weight growth of rats in the model group slowed down significantly from the second week, while the arthritis index and joint swelling degree increased significantly. The joints of rats were red and swollen and could not bear weight, while sargentgloryvine stem could significantly improve the related symptoms of CIA rats, such as reducing foot swelling, arthritis index score and improving body weight data. The levels of TNF-α, IL-1β, IL-6 and IL-18 in serum and the expressions of RANKL, p-IκB-α, NF-κB/p65, NF-κB/p65, NLRP3 and Caspase-1 in synovial joint of model group were significantly higher than those in normal group (P < 0.01), while the above indexes in sargentgloryvine stem middle and high dose groups were significantly lower than those in model group (P < 0.05, P < 0.01). CONCLUSION Sargentgloryvine stem can improve the inflammatory response and delay the pathological progress of CIA rats, and the mechanism may be related to the reduction of pro-inflammatory cytokines release and the inhibition of NF-κB/NLRP3 signal pathway.

Effect of Evodiamine Combined with Chloroquine on Hepatocarcinoma

SHEN Xing-xing, SHI Le, YAO Liang-yu, NIU Yu-zhen, LIANG Tao

2021, 37(3): 400-403. doi: 10.14148/j.issn.1672-0482.2021.0400

[Abstract](187) [FullText HTML] (39) [PDF 1430KB](108)

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OBJECTIVE To study the anti-liver cancer effect of evodiamine (EVO) combined with the autophagy inhibitor chloroquine (CQ).METHODS CCK8 method was used to detect the EVO and EVO+CQ on HepG2 cell vitality. Western blot method was used to detect LC3Ⅱ / LC3Ⅰ, P62, vascular endothelial growth factor (VEGFA) protein expressions. ELISA method was applied to detect VEGFA expression level in the supernatant fluid of HepG2 cells. The effect of cell conditioned medium on HUVEC cell invasion ability was tested.RESULTS Different concentrations of EVO could significantly inhibit the activity of HepG2 cells in a dose-dependent manner after 24 hours. When combined with CQ, the inhibitory activity was stronger (P < 0.01). Western blot results showed that EVO could up-regulate the expression of LC3Ⅱ/LC3Ⅰ (P < 0.05) and reduce that of P62 (P < 0.05), but show no significant effect on VEGFA, although a downward trend was observed. The results of MDC staining showed that EVO could increase autophagosomes in HepG2 cells. When combining EVO and CQ, the accumulation of autophagosomes in HepG2 cells increased significantly. ELISA results showed that EVO reduced the expression of VEGFA (P < 0.01), and much significantly when combining EVO and CQ (P < 0.01). The HUVECs invasion experiments showed that EVO effectively inhibited the invasion of HUVECs (P < 0.01), and much significantly when combining EVO and CQ (P < 0.01).CONCLUSION Evodiamine can inhibit the activities of HepG2 cells, increase the autophagy level and reduce the angiogenesis. Evodiamine shows more potent inhibitory activities against HepG2 and angiogensis, when it is combined with chloroquine.

Preparation and in vivo and vitro Evaluation of pH-Sensitive Liposomes Loading Arsenic Trioxide

HUANG Jian-yu, WANG Yong-ming, WANG Ruo-ning, DI Liu-qing

2021, 37(3): 404-410. doi: 10.14148/j.issn.1672-0482.2021.0404

[Abstract](151) [FullText HTML] (28) [PDF 1811KB](283)

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OBJECTIVE To prepare pH-sensitive liposomes with arsenic trioxide and evaluate the anti-glioma activity in vitro and safety in vivo.METHODS The hydrophobic modified MnAs coprecipitates were prepared by reverse phase microemulsion method, and liposomes loaded with MnAs coprecipitations (Liposome/MnAs) were prepared by emulsion evaporation method. The particle size, PDI and Zeta potential of Liposome/MnAs were measured. The morphology of Liposome/MnAs was observed by transmission electron microscopy. Encapsulation efficiency was determined by inductively coupled plasma mass spectrometer. Dialysis bag method was used to investigate the drug release characteristics under different pH conditions in vitro. The ability of in vitro MRI imaging was investigated under acidic conditions. The uptake and intracellular distribution of Liposome/C6 in mouse derived glioma cells GL261 were observed by confocal microscopy. The toxicity of free arsenic trioxide and Liposome/MnAs on GL261 was investigated by thiazolium blue assay. The apoptosis effect of free arsenic trioxide and Liposome/MnAs on GL261 cells was detected by flow cytometry. Liposomes were labeled with coumarin 6.RESULTS The prepared MnAs coprecipitations were hydrophobic and could be dissolved by chloroform well. Liposome/MnAs were spherical in shape, with a particle size of (286.43±6.41) nm and As encapsulation efficiency of (48.32±5.95)%. It could quickly respond to release As³⁺ and Mn²⁺ under the condition of pH 5.4, and had a good ability of in vitro MRI imaging Cell uptake assay showed that GL261 cells had a good uptake of C6-labeled liposomes, which were mainly distributed in the cytoplasm. The inhibitory effect of Liposome/MnAs on GL261 cell growth was higher than that of free arsenic trioxide, and the IC₅₀ decreased from 4.74μmol/L to 2.99μmol/L. Apoptosis experiments also showed that Liposome/MnAs had a better effect on promoting the apoptosis of GL261 cells than free arsenic trioxide, and the proapoptotic rate was increased from 13.73% to 21.42%. Liposome/MnAs had no obvious toxicity to the main organs in mice within an administration cycle.CONCLUSION The MnAs coprecipitates prepared by reverse microemulsion method have good hydrophobicity and can be encapsulated to by liposome prepare Liposome/MnAs, which had pH-responsive drug release characteristics, could enhance ATO uptaked by glioma cell GL261. The Liposome/MnAs enhanced the toxicity of arsenic trioxide to GL261 cell and had certain safety in vivo.

Preparation and in vivo and in vitro Study of Piperine-Theanine Co-Amorphous Complex

HUANG Li-hua, SHEN Hua, HAN Yi

2021, 37(3): 411-418. doi: 10.14148/j.issn.1672-0482.2021.0411

[Abstract](226) [FullText HTML] (47) [PDF 1963KB](110)

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OBJECTIVE To prepare piperine-theanine co-amorphous complex (PIP-THE CAC) and improve dissolution and bioavailability of PIP.METHODS The PIP-THE CAC was prepared by quench cooling, characterized by DSC, XRPD, FTIR, SEM and evaluated by in vitro dissolution under sink and non-sink conditions. The physical stability of PIP-THE CAC was also investigated. Besides, the bioavailability study of PIP-THE CAC was conducted by pharmacokinetic tests in rats.RESULTS DSC and XRPD indicated that PIP-THE CAC was successfully prepared. FTIR confirmed that there was intermolecular hydrogen bond interaction between PIP and THE in the prepared CAC, resulting in excellent physical stability. SEM showed that the CAC was irregular, lumpy and granular, and the characteristics of PIP and THE were disappeared. Besides, compared with pure PIP and PIP-THE physical mixture, PIP-THE CAC possessed a higher dissolution rate and a higher dissolution degree, and maintained supersaturated degree for long time in vitro dissolution experiments. Pharmacokinetic results showed that C_max, t_max, AUC_{0-24 h} and AUC_0-∞ of PIP-THE CAC group increased significantly (P < 0.01) compared with raw PIP, and the C_max and bioavailability of PIP increased by 2.03 and 1.93 times, respectively (P < 0.01).CONCLUSION PIP-THE CAC prepared by THE co-amorphization with PIP can effectively improve the solubility/dissolution and oral bioavailability of PIP.

Study on Determination of Multi-Index Components and UPLC Fingerprint of Standard Decoction of Qingxin Jieyu Formula

LI Mei, CHEN Sheng-jun, WANG Xie-he, JIANG Zhong-hui, LI Ling-ling, XU Yi-liang, DI Liu-qing, GAO Zhu-ye

2021, 37(3): 419-427. doi: 10.14148/j.issn.1672-0482.2021.0419

[Abstract](180) [FullText HTML] (46) [PDF 1799KB](122)

Abstract:
OBJECTIVE To prepare 18 batches of standard decoction of Qingxin Jieyu Formula and study its substance benchmarks. METHODS The contents and transfer rates of salvianolic acid B, ferulic acid, total alkaloids, astragaloside Ⅳ, as well as extraction rate, oil content and fingerprint similarity of standard decoction were used as evaluation indexes to establish the allowable range of characterization parameters of standard decoction of Qingxin Jieyu Formula. The fingerprint similarity evaluation system software (2012 version) was used for fingerprint analysis, and cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to evaluate the fingerprint common peak. RESULTS A total of 18 common peaks were determined, with the common peak similarity greater than 0.90. It was found that 18 batches of samples were grouped into two groups, and combined with the results of similarity, this difference may be related to the slices compatibility of different producing areas. According to the OPLS-DA VIP value combined with the load diagram, three peaks affecting the quality of the batch samples were selected, which were salvianolic acid B (peak 14), copithine hydrochloride (peak 10) and ferulic acid (peak 7) in turn. In order to reduce the quality difference between batches of samples and ensure the consistency of preparation quality, the medicinal materials from the same production area should be selected as far as possible in the subsequent preparation production. CONCLUSION The preparation method of standard decoction of Qingxin Jieyu Formula is stable, the multi-index content determination method is simple and fast, the fingerprint method is stable and the similarity is high, which can provide reference for the quality control of the subsequent preparation of Qingxin Jieyu Formula.

Studies on the Metabolites of Caudatin-3-O-β-D-Cymaropyranoside in Rats

SHI Jian-feng, PENG Zi-xuan, PENG Yun-ru, YAO Xiao-ming, CHEN Yun

2021, 37(3): 428-433. doi: 10.14148/j.issn.1672-0482.2021.0428

[Abstract](181) [FullText HTML] (21) [PDF 1522KB](124)

Abstract:
OBJECTIVE To study the rats' metabolism of caudatin-3-O-β-D-cymarose glycosides, a kind of sterioside in Radix Cynanchi Auriculati. METHODS Rats were given the a single dose of caudatin-3-O-β-D-cymarose glycosides by intragastric administration (20 mg/kg). Then the rats' plasma, urine, feces, and bile during the following 24 hours were collected. In addition, the processed samples were analyzed by UPLC-Q-TOF with MetabolynxTM software for the preliminary measurement of the metabolites of caudatin-3-O-β-D-cymarose glycosides in rats' plasma, urine, feces, and bile. RESULTS The original, hydrolytic and demethylated metabolites of caudatin-3-O-β-D-cymarose glycosides were found in plasma, urine, feces, and bile samples, specifically, the original caudatin-3-O-β-D-cymarose glycosides in urine, hydrolytic metabolites in plasma and bile, two methylated metabolites in feces, along with one methylated and three demethylated metabolites in bile. CONCLUSION The metabolism of caudatin-3-O-β-D-cymarose glycosides in rats is extensive, and the main types of metabolism are hydrolysis and demethylation.

Professor Wu Xu's Experience in the Treatment of Interstitial Cystitis with Tongdu Wenyang Acupuncture

TANG Ping-ping, LI Jian-bing, XU Yan-zhi, BAO Chao

2021, 37(3): 434-436. doi: 10.14148/j.issn.1672-0482.2021.0434

[Abstract](267) [FullText HTML] (78) [PDF 1139KB](112)

Abstract:
The paper introduced the clinical experience of Professor Wu Xu, a well-known veteran traditional Chinese medicine doctor, in treating interstitial cystitis with "Tongdu Wenyang acupuncture". According to the etiology and pathogenesis of interstitial cystitis, Professor Wu proposed the therapeutic principles and methods under the guidance of the theory of "Tongdu Wenyang", that is, promoting the governor channel, harmonizing the resonance of qi, warming yang, coordinating the conception channel and the governor channel, dredging the belt channel, regulating the liver meridian, along with activating qi and blood. Meanwhile, the focus should be reached and the arrival of qi should be obtained with rectifying and regulating qi during needling. In addition, Professor Wu attached much importance in relaxing the mind, observing and maintaining the spirit, as well as giving psychological counseling during the process of needling, thus dredging the governor channel and yang meridians, harmonizing qi and blood, relieving symptoms and revoering the physiological function of bladder.

Professor Pan Liqun's Experience of Treating Diarrhea after Esophageal Cancer Surgery with the Method of Raising Yang and Lifting the Sunken Qi

ZHOU Guo-wei, WU Bei-bei, GUO Shun, LI Ming

2021, 37(3): 437-438. doi: 10.14148/j.issn.1672-0482.2021.0437

[Abstract](240) [FullText HTML] (57) [PDF 1123KB](133)

Abstract:
Professor Pan Liqun treats the complication of diarrhea after esophageal cancer surgery with the method of raising yang and lifting the sunken qi. It is believed that the etiology and pathogenesis of diarrhea after esophageal cancer surgery is induced by surgery, which manifests as spleen and stomach damage, the sinking of center qi, a decline of vital gate fire, as well as yang deficiency of spleen and kidney for the long duration. With the weakness of the spleen and stomach as the basis, and marked by the injury by six excesses, improper diet and emotions, the syndrome of intermingled deficiency and excess often occurs. Deficiency of the spleen and sinking of qi, along with the failure of spleen transportation is the key feature of the disease. The fundamental treatment method should be raising yang and lifting the sunken qi. The prescription should be modified Shengxian decoction based on syndrome differentiation to generate spleen yang, harmonize the ascending and descending of spleen and stomach, promote the recovery of spleen transportation, thus cure diarrhea.

A Textual Research on the Key Information of the Famous Classical Formula Wendan Decoction Based on Ancient Bibliometric Analysis

CHEN Ren-shou, LI Yu, LU Yue, LI Lu-jie

2021, 37(3): 439-445. doi: 10.14148/j.issn.1672-0482.2021.0439

[Abstract](265) [FullText HTML] (57) [PDF 1225KB](161)

Abstract:
Through systematically collating, textual researching and analyzing ancient literatures on Wendan decoction, we sorted out the historical development of Wendan decoction and correctly understood the key issues of its formula composition, chief indications, formula meaning, dosage and drug processing, so as to provide literature data to support the development and modern clinical application of the famous classical formula. The bibliometric method was used to collect the literatures related to Wendan decoction in Chinese medical classics. Therefore, we obtained 197 relevant ancient literatures, involving 84 Chinese medical classics. After analysis and textual researching, it was concluded that Wendan decoction was derived from the lost medical formulary, Ji Yan Fang, written by Yao Sengyuan in the Northern and Southern dynasties. Then that formula, which was transcribed into the medical classics, Qian Jin Yao Fang, by Sun Simiao in the Tang dynasty, consisted of six medicines, namely, Rhizoma Zingiberis Recens, Rhizoma Pinelliae, Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Caulis Bambusae in Taenia, and Radix et Rhizoma Glycyrrhizae. Besides, its chief indications had been expanded, including insomnia, palpitations, severe palpitations and vomiting. However, the understanding of that formula meaning had varied from generation to generation. All the drugs in Wendan decoction are used in raw form, except for "Rhizoma Pinelliae processed in ginger juice", "Fructus Aurantii Immaturus fried with wheat bran" and "dry-fried Radix et Rhizoma Glycyrrhizae". The specific processed method is in accordance with the 2020 edition of the Chinese pharmacopoeia. The reference dosage of Wendan decoction is Rhizoma Pinelliae 10 g, Fructus Aurantii Immaturus 10 g, Caulis Bambusae in Taenia 10 g, Pericarpium Citri Reticulatae 15 g, Rhizoma Zingiberis Recens 20 g and Radix et Rhizoma Glycyrrhizae 5 g. In addition, the specific decoction method is decocting medicinal ingredients with 1 600 mL water and taking 400 mL decoction, which was then divided into two portions to be warmed and taken after breakfast and dinner". When taking this decoction, patients should avoid taking cold, greasy and stimulating foods in addition to mutton, seaweed, pakchoi seedling and cerealose.

Quality Research and Key Technology of the Quantity Value Transfer of TCM Classical Prescription

HUANG Shi-wen, YAN Yuan-yuan, JI Jing, WANG Qi, ZHANG Xiao-yun, HE Rui-xin, CHENG Jian-ming

2021, 37(3): 446-449. doi: 10.14148/j.issn.1672-0482.2021.0446

[Abstract](366) [FullText HTML] (98) [PDF 1151KB](166)

Abstract:
In recent years, the research and development of TCM classical prescription is a hot spot in the Chinese medicine industry. In order to solve the problem of quality difference between batches of TCM Patent Prescription, the author of this paper elaborate the key factors affecting the quality of TCM classical prescription and the key techniques affecting the quantity value transfer through the level of medicinal material, herbal decoction pieces, Material baseline and preparations, according to the declaration information demand of Material baseline and TCM Patent Prescription.

Optimization of Water Extracting Procession of Qingwei San through Multi-Targets Integrated Weighted Method

LIU Huan-huan, ZHANG Qian, XU Ting-ting, WANG Ying-zhuo, WANG Jue, ZHANG Lin-gang, YAO Yi, ZHANG Xian-lin, LIU Shi-jia

2021, 37(3): 450-456. doi: 10.14148/j.issn.1672-0482.2021.0450

[Abstract](274) [FullText HTML] (67) [PDF 1921KB](113)

Abstract:
OBJECTIVE To optimize the extraction process of the classic prescription Qingwei San by using a multi-index comprehensive weighted scoring method combined with orthogonal experiment. METHODS The amount, time and times of decoction were taken as the influencing factors. The indicators concluded the similarity of high performance liquid chromatography (HPLC) characteristic fingerprint chromatograms, the rate of extraction and the contents of isoferulic acid, ferulic acid, verbascoside, berberine hydrochloride and paeonol. The analytic hierarchy process (AHP) combined with the index correlation weight method (CRITIC) was used to determine the weight of each indicator. The decoction process of Qingwei San was optimized combined with the orthogonal experiment to calculate the comprehensive score. RESULTS Finally, the optimized decoction process of Qingwei San was determined as the following. 24 g of coarse powder of the decoction pieces was taken into the pot, and 12 times the amount of water were added into the container and soaking for 30 minutes. The decoction was heated for 60 minutes with gentle fire after boiling with high heat, and extracted for twice. The decoction was concentrated to 200 mL after filtering. Following the optimized method, the extraction rate of Qingwei San was more than 39.99%, the similarity of characteristic fingerprint chromatograms was above 0.964. The main components of ferulic acid, isoferulic acid, verbascoside, berberine hydrochloride and paeonol were 0.061%, 0.535%, 0.060%, 0.261% and 0.054%, respectively. CONCLUSION The characteristic fingerprint chromatograms could better represent the information of the whole prescription of Qingwei San and the main representive components. The optimized decoction process reflects the comprehensive decoction quality of Qingwei San better, which is convenient for the operation in medical institutions. It will provide the basis for the study of the components in the standard decoction of Qingwei San, and an experimental reference for the development and research of granules of traditional Chinese medicine formulations in the future.

Research Progress in Antineoplastic Mechanism of Triptolide and Toxicity Attenuation by Compatibility

SONG Yi, LIU Yan, FANG Bing-qian, KANG Di, HU Li-hong

2021, 37(3): 457-464. doi: 10.14148/j.issn.1672-0482.2021.0457

[Abstract](344) [FullText HTML] (621) [PDF 1334KB](211)

Abstract:
Triptolide (TP) is a kind of natural triepoxide diterpenoid, isolated from Chinese medical herb Tripterygium wilfordii Hook F. As one of the primary biologically active ingredients, TP possesses various and potent pharmacological effects such as anti-inflammatory, immunosuppressive and anti-tumor properties. Here, we focus on the mechanisms of actions of TP in anti-tumor effects, the toxicity and the possible solutions in toxicity attenuation by compatibility. This review may provide reference for the clinical development of TP as well as its related derivatives.

Progress on Gut Microbiota-Regulated Bone Metabolism Imbalance and Implications for Chinese Medicine Intervention

WEI Wei, CHEN Ling, ZHOU Yong-jin, XU Zhui-cheng, LI Wan-hong, WEI Ai-chun, HUANG Gui-cheng

2021, 37(3): 465-472. doi: 10.14148/j.issn.1672-0482.2021.0465

[Abstract](298) [FullText HTML] (49) [PDF 1384KB](204)

Abstract:
Gut microbiota has the most category and highest density among all microbial habitats in human body. They can regulate human physiological functions and immune status through gut microbiota-host metabolism and then maintain our healthy. Recently, accumulating clinical researches and preclinical studies have reported that gut microbiota can regulate bone metabolism through various ways. For example, alterations in microbiota composition induced by a variety of pathological states and medicine, especially the antibiotics, may contribute to pathological bone loss. With the development of some new techniques such as high-throughput sequencing, gene knockout and germ-free mice, the recent studies implicated that gut microbiota can regulate bone metabolism balance through direct regulation, the metabolism of endogenous substances and the alterations of related hormones. This review describes recent data uncovering the relationship between gut microbiota and bone metabolism, with a focus on potential regulating pathways and Traditional Chinese Medicine intervention. The implications for treatment of bone metabolism disorders such as osteoporosis and drug target research are discussed as well.

Progress on TCM Interventions of COVID-19 in Recovery Period

SHI Suo-fang, ZHANG Xiao-na, WANG Bo-han

2021, 37(3): 473-476. doi: 10.14148/j.issn.1672-0482.2021.0473

[Abstract](764) [FullText HTML] (106) [PDF 1174KB](263)

Abstract:
COVID-19 is an acute respiratory disease caused by the infection of SARS-CoV-2. In addition to pulmonary lesions, it can also cause damage to multiple systems outside the lung. Traditional Chinese medicien (TCM) treatment based on syndrome differentiation can take account of both strengthening the body and eliminating evil, and thus effectively improve the sequelae of COVID-19 during the recovery period. This article summarizes the research status of COVID-19 recovery period and the intervention idea of TCM, in order to provide perspectives for further studies in the sequelae of COVID-19 and TCM interventions of COVID-19 during recovery period.

Research Status and Prospect of Cancerous Toxin Theory

HONG Jing, ZHAO He-tong, YU Song, YAO Man, NIE Shu-chang, ZHAI Xiao-feng

2021, 37(3): 477-480. doi: 10.14148/j.issn.1672-0482.2021.0477

[Abstract](247) [FullText HTML] (126) [PDF 1159KB](183)

Abstract:
In terms of the concept, yin-yang property, pathogenesis and transformation rules of cancerous toxin, the paper summarizes the research status of cancerous toxin, draws that there is no unified understanding of the concept, etiology, and pathogenesis, and the yin-yang property, transformation rules of cancerous toxin deserved further study. Moreover, it proposes the prospects of cancerous toxin, including unifying the concept of cancerous toxin in the academic circles, constructing the syndrome differentiation of cancerous toxin theory in different cancers, improving the study of the transformation rules of cancerous toxin, promoting the integration of Chinese medicine and Western medicine in the treatment of malignant tumor, thus realizing the construction of clinical-oriented cancerous toxin theory.

2021 Vol. 37, No. 3

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