南京中医药大学学报

From "Numerical Value" to "Syndrome and Target": A Review of the Concept and Strategy of Hypertension Treatment in Chinese Medicine

FANG Zhu-yuan, WANG Xin-dong

2022, 38(4): 279-284. doi: 10.14148/j.issn.1672-0482.2022.0279

[Abstract](814) [FullText HTML] (213) [PDF 2559KB](56)

Abstract:
A brief summary of the concepts, strategies, methods and mechanisms of Chinese medicine treatment for hypertension in recent years is presented, focusing on the conceptual shift of endpoint events from emphasizing the numerical value of blood pressure to syndromes and target organs, and the strategic shift from "meeting the blood pressure standard" to "sooner meeting the standard", as well as the progress in inheriting and expanding the pathogenesis theory, scientifically interpreting the connotation of syndrome, innovating and optimizing the use of prescriptions, and elucidating the mechanisms of pharmacological targets. In response to the problems of insufficient understanding and inheritance, short of innovation, and flimsy evidence of "reaching the target at the initial stage", we propose the research strategy of "the combination of numerical value-syndrome-target" for the prevention and treatment of hypertension with Chinese medicine and its efficacy evaluation, with the research orientation of "differentiation, complementation, and comparative advantage" of the western medicine treatment, together with the research idea of "regarding the research starting point as the ending point of heart, brain, and kidney". In addition, we analyze and prospect the frontier exploration directions in terms of clarifying our own positioning, exploring the art of integration, keeping the positive and upgrading development, expanding the formulae thinking, accumulating evidence-based facts, innovating evaluation methods, and elucidating target mechanisms.

Clinical Study Based on Shear Wave Elastography to Evaluate the Efficacy of Qianyang Yuyin Granules in Reducing Early Renal Damage in the Hypertensive Elderly with the Syndrome of Yin Deficiency and Yang Hyperactivity

FANG Yuan, ZHANG Bei-bei, HUANG Hui, DING Kang, XU Xi-ru, PAN Ming-yao, WANG Han

2022, 38(4): 285-290. doi: 10.14148/j.issn.1672-0482.2022.0285

[Abstract](222) [FullText HTML] (52) [PDF 1060KB](19)

Abstract:
OBJECTIVE To evaluate the efficacy of Qianyang Yuyin Granules in reducing the early renal damage and renal fibrosis in the hypertensive elderly with the syndrome of yin deficiency and yang hyperactivity based on shear wave elastography (SWE). METHODS Through randomized controlled trial, we accepted 40 renal-damage cases of the hypertensive elderly with the syndrome of yin deficiency and yang hyperactivity who met the inclusion criteria. The control group was given standard treatment with angiotensin Ⅱ receptor blocker (ARB) or combined with calcium channel blocker (CCB) drugs, while the treatment group was treated with Qianyang Yuyin Granules on top of the therapy in the control group. The course of treatment lasted for 12 weeks. In addition, we observed the changes of the syndrome scores of traditional Chinese medicine (TCM), clinical efficacy, blood pressure, transforming growth factor-β1 (TGF-β1), hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C), N-terminal peptide of type Ⅲ procollagen (PⅢ NP), urinary neutrophil gelatinase-associated lipid transport protein (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), as well as renal Young's modulus values before and after treatment. RESULTS After treatment, the TCM syndrome scores of both groups were reduced (P < 0.05, P < 0.01), but the treatment group was better than the control group in relieving the symptoms of vertigo, lumbago, vexing heat in the five centers, palpitations, and total scores (P < 0.05, P < 0.01). Thus, the TCM clinical efficacy of the treatment group was better than that of the control group (P < 0.05). Besides, the systolic pressure and pulse pressure difference of the treatment group dropped (P < 0.05, P < 0.01). At the meantime, some Serum fibrosis indexes such as TGF-β1, HA, LN and PⅢ NP expression levels were significantly decreased in the treatment group (P < 0.05), whose results were better than those in the control group (P < 0.05). Likewise, urinary KIM-1 and IL-18 levels of renal tubular injury markers were significantly decreased in the treatment group (P < 0.01), whose results were better than those in the control group (P < 0.01). In addition, the Emean value of Young's modulus was significantly decreased in the treatment group (P < 0.01), whose result was better than that in the control group (P < 0.05). No evident adverse reactions were observed in the two groups during the treatment course. CONCLUSION Qianyang Yuyin Granules can reduce early renal damage and renal fibrosis in elderly hypertensive patients with the syndrome of Yin deficiency and Yang hyperactivity.

Clinical Study on Early Intervention of Qianyang Yuyin Granules to Slow Progression of Leukoencephalopathy in Hypertensive Patients with Cognitive Impairment

YAN Xi-wu, MENG Ting, LIU Jin-feng, HONG Yu-xing, KANG Jiao-yang, LIU Huai-jun, CHANG Cheng

2022, 38(4): 291-297. doi: 10.14148/j.issn.1672-0482.2022.0291

[Abstract](270) [FullText HTML] (73) [PDF 1767KB](22)

Abstract:
OBJECTIVE To observe the clinical efficacy of Qianyang Yuyin Granules in the treatment of hypertensive patients with cognitive impairment and the effect on their leukoencephalopathy volume. METHODS The patients were randomly divided into 64 cases in the treatment group, 33 cases in the control group, and 34 cases in the donepezil group by randomized controlled, multicenter enrollment. In the control group, the patients were treated with conventional western medicine, while in the treatment group and donepezil group, the patients were separately treated with Qianyang Yuyin Granules and donepezil based on the therapies in the control group. The course of the treatment was 6 months.The changes of blood pressure, leukoencephalopathy volume, Mini-Mental State Examination (MMSE), Vascular Dementia Assessment Scale (VaDAS-cog), as well as traditional Chinese medicine (TCM) syndrome score were compared before and after treatment in the three groups. Besides, the changes of safety indexes such as blood routine examination, liver and kidney function were also observed. RESULTS After treatment, blood pressure was lowered significantly in all three groups (P < 0.01), with no significant differences between each groups(P>0.05). The TCM syndrome score were reduced in all three groups (P < 0.01), while the treatment group showed better results than the control group and the donepezil group did (P < 0.01). The leukoencephalopathy volumes were increased significantly in all three groups (P < 0.01), but the increase of leukoencephalopathy volume in the treatment group was less than that in the control group and the donepezil group (P < 0.05). MMSE scores were increased significantly in the treatment group (P < 0.01), whose results were better than those in the control group and the donepezil group (P < 0.01). VaDAS-cog scores were decreased significantly in the treatment group (P < 0.01), whose results were also better than those in the control group (P < 0.01). In addition, no significant adverse reactions were observed in any of the three groups during the treatment period. CONCLUSION The Qianyang Yuyin Granules can notably improve the cognitive function of hypertensive patients, and can evidently slow their progression of leukoencephalopathy with safety.

Treatment of Endometriosis from "Yang" Perspective

ZHANG Yu-han, XIA Gui-cheng, TAN Yong

2022, 38(4): 298-302. doi: 10.14148/j.issn.1672-0482.2022.0298

[Abstract](327) [FullText HTML] (86) [PDF 1017KB](49)

Abstract:
According to the theory of "six yang", Professor Xia Guicheng, a master of traditional Chinese medicine, pointed out that the key to the pathogenesis of endometriosis is "yang deficiency leading to stasis obstruction". On top of that, he considered that the treatment should not only promote blood circulation to remove blood stasis, and regulate menstruation to relieve pain, but also follow the female physiological cycle by using sequential therapy of regulating cycle. In conclusion, the particular attention must be paid to the transformation of yin and yang during intermenstruum and the continuation of extreme yang and the reaching of six yang during the premenstruum to maintain the dynamic balance of yin and yang in the patient's body, which provides a new idea for the treatment of endometriosis.

Expert Consensus on San-fu Herbal Patch Intervention for Pediatric Asthma

ZHAO Xia, QIN Yan-hong, WU Jian-xin, LIU Zhu-yun, LI Min, YANG Jiang, WU Li-qun, JIANG Zhi-yan, GAO Yan, LONG Hong-yan, ZHAI Wen-sheng, XUE Zheng, WEI Wei

2022, 38(4): 303-307. doi: 10.14148/j.issn.1672-0482.2022.0303

[Abstract](284) [FullText HTML] (57) [PDF 1033KB](43)

Abstract:
On the basis of literature retrieval, literature evaluation and literature summary, three rounds of expert questionnaires were conducted by Delphi method. After expert demonstration meeting, expert quality methodological evaluation, and clinical consistency evaluation, the Expert Consensus on San-fu Herbal Patch Intervention for Pediatric Asthma was formed, proposing an expert consensus on the scope, terminology and definitions, diagnosis, staging, applicable population, application methods and contraindications, as well as precautions and regulation of the San-fu herbal patch intervention for pediatric asthma, in order to standardize the clinical application of this therapy. This consensus applies to medical institutions at all levels and is intended for clinicians in Chinese medicine, pediatrics, child health centers, and treatment centers, targeting children aged 1 to 18 years with asthma in protracted and remission stage.

Study on the Mechanism of Tanshinone ⅡA against Coronary Heart Disease with Comorbid Depression in ApoE^-/- Mice

KONG Jun-hong, CHEN Xuan, SHA Chen-xi, GONG Chu-qiao, SONG Xiao-long

2022, 38(4): 308-314. doi: 10.14148/j.issn.1672-0482.2022.0308

[Abstract](169) [FullText HTML] (61) [PDF 3145KB](25)

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OBJECTIVE To investigate the effect and mechanism of tanshinone ⅡA against coronary heart disease with comorbid depression in ApoE^-/- mice. METHODS The model of coronary heart disease with comorbid depression was established by feeding high fat diet and carrying out chronic unpredictable mild stress (CUMS). Mice were randomly divided into normal group, model group, tanshinone ⅡA low dose group (30 mg · kg^-1) and tanshinone ⅡA high dose group (60 mg · kg^-1). Hematoxylin-eosin (HE) and oil red O staining were used to detect the pathological changes of cardiac aortic sinus in ApoE^-/- mice. Forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to observe the depression-like behaviors of ApoE^-/- mice. The levels of blood lipid and inflammatory factors were detected by ELISA assay. The expressions of inflammation related proteins in cardiac aortic sinus and hippocampus were detected by Western blot. RESULTS Compared with the normal group, the lipid accumulation in the cardiac aortic intima in the model group increased significantly, the levels of blood lipid and pro-inflammatory factors increased significantly (P < 0.01), the immobility time of FST and TST significantly increased (P < 0.01), while the sucrose preference rate of SPT significantly decreased (P < 0.01), the ratios of p-GSK3β (Ser9)/GSK3β, p-NF-κB/NF-κB and p-CREB (Ser133)/CREB in cardiac aortic sinus and hippocampus increased significantly (P < 0.01). Compared with the model group, the treatment with tanshinone ⅡA significantly reduced the accumulation of lipid in cardiac aortic intima, the levels of blood lipid and pro-inflammatory factors and the immobility time of FST and TST decreased significantly (P < 0.01), the sucrose preference rate of SPT significantly increased (P < 0.01), the ratio of p-NF-κB/NF-κB decreased significantly (P < 0.01), and the ratios of p-GSK3β(Ser9)/GSK3β and p-CREB(Ser133)/CREB increased significantly (P < 0.05, P < 0.01). CONCLUSION Tanshinone ⅡA has a significant effect against coronary heart disease with comorbid depression in ApoE^-/- mice, and its mechanism may be related to the regulation of GSK3β, and further activation of NF-κB and CREB.

Effect of Quyu Humo Paste on the Repair of Esophageal Mucosa in Rats with Reflux Esophagitis by Regulating NLRP3/Caspase-1 Signaling Pathway

XU Xin-yi, YANG Xin, LIANG Guo-qiang, ZHU Hui-ping, HUANG Xue, WANG Ai-min, SUN Hong-wen

2022, 38(4): 315-322. doi: 10.14148/j.issn.1672-0482.2022.0315

[Abstract](224) [FullText HTML] (75) [PDF 3402KB](16)

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OBJECTIVE From the perspective of esophageal mucosal barrier repair, to explore the effect of Quyu Humo paste on nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3)/aspartate specific cysteine protease-1 (Caspase-1) signal pathway in rats with reflux esophagitis (RE), and to reveal the mechanism of Quyu Humo paste in the treatment of RE. METHODS Rats were randomly divided into blank group (n=10), model group (n=10), western medicine group (n=10), low dose Quyu Humo paste group (n=10), middle dose Quyu Humo paste group (n=10) and high dose Quyu Humo paste group (n=10). Except the blank group, the RE rat model was established by "4.2 mm pyloric clip+2/3 gastric fundus ligation" in the other 5 groups. The rats in the blank group and model group were given starch+distilled water, each doses of Quyu Humo paste groups were treated with Quyu Humo paste of 0.54, 1.62, 4.86 g·kg^-1, respectively, and western medicine group were given aluminum and magnesium plus suspension for 14 d. On the 15th day, the rats were killed and the esophageal tissues were taken out. The contents of Caspase-1, IL-1β and IL-18 in serum were detected by ELISA method, the protein expressions of NLRP3 and Caspase-1 in esophageal tissue were detected by Western blot, and the pathological changes of esophageal tissue were observed under light microscope with HE staining. RESULTS The protein expressions of Caspase-1, IL-1β, IL-18 in serum and NLRP3 and Caspase-1 in esophageal tissue in the model group were significantly higher than those in the blank group (P < 0.001). Compared with the model group, the contents of Caspase-1, IL-1β, IL-18 in serum and the protein expressions of NLRP3 and Caspase-1 in esophageal tissue decreased significantly in western medicine group, middle and high dose Quyu Humo paste groups (P < 0.001). Compared with the western medicine group, the protein expressions of NLRP3 and Caspase-1 in esophageal tissue and Caspase-1 in serum significantly decreased in the high dose Quyu Humo paste group (P < 0.01, P < 0.001). CONCLUSION Quyu Humo paste can improve the injury of esophageal epithelium, repair esophageal mucosa and promote the healing of reflux esophagitis in rats by inhibiting the excessive activation of NLRP3 signal pathway, down-regulating the expression of Caspase-1, reducing the levels of IL-1β and IL-18, and antagonizing esophageal inflammation.

The Invasion and Migration Effects of Huayu Xiaozheng Granules on Human Chorionic Trophoblast Cells through Regulating Talin1

QIU Pin, YUAN Shuo, DENG Gao-pi

2022, 38(4): 323-330. doi: 10.14148/j.issn.1672-0482.2022.0323

[Abstract](148) [FullText HTML] (63) [PDF 3037KB](18)

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OBJECTIVE To study the effects of Huayu Xiaozheng Granules containing serum on the proliferation, invasion and migration of HTR-8/SVneo cells, and to explore its mechanism. METHODS Huayu Xiaozheng Granules containing serum was prepared, and CCK8 test was conducted to detect the effects of different concentrations and doses of Huayu Xiaozheng Granules containing serum on HTR-8/SVneo cell proliferation, and to screen the optimal concentration and dose of subsequent experimental drugs. Scratch test and Transwell test were used to detect the effects of Huayu Xiaozheng Granules containing serum on the invasion and migration of HTR-8/SVneo cells. The mRNA and protein expressions of Talin1, MMP-2, N-cadherin and Snail and the pathway proteins Rap1GAP and ITGB3 in HTR-8/SVneo cells were detected by qPCR and Western blot. RESULTS Huayu Xiaozheng Granules containing serum inhibited the proliferation, invasion and migration of HTR-8/SVneo cells. Compared with blank control group, Huayu Xiaozheng Granules containing serum down-regulated the expressions of invasion related factors Talin1, MMP-2, N-cadherin and Snail (P < 0.05, P < 0.01) and the expressions of pathway proteins Rap1GAP and ITGB3 in HTR-8/SVneo cells (P < 0.05, P < 0.01). CONCLUSION Huayu Xiaozheng Granules containing serum can down-regulate the expression of Talin1 through regulating Rap1/Talin1/ITGB3 signaling pathway.

Study on Anti-Melanoma Mechanism of Sparganii Rhizoma Extract Inhibiting Glycolysis Rate-limiting Enzyme

LIU Yang, ZHENG Xiu-qin, YANG Ge-jun, ZHAO Han, LU Yin, WANG Ai-yun, CHEN Wen-xing

2022, 38(4): 331-338. doi: 10.14148/j.issn.1672-0482.2022.0331

[Abstract](228) [FullText HTML] (38) [PDF 3796KB](21)

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OBJECTIVE To explore the molecular mechanism of Sparganii Rhizome anti-melanoma and its effective material basis. METHODS The active ingredients and corresponding targets of Sparganii Rhizome were retrieved through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the melanoma disease targets were retrieved by GeneCards database. The drug-disease target protein-protein interaction (PPI) was constructed by the cytoscape 3.7.2 software. The core targets were screened out and uploaded to the DAVID platform for KEGG pathway enrichment analysis. Further verification was carried out through cell proliferation and activity detection (CCK-8) experiment, EdU proliferation testing experiment, Seahorse XF cell mito stress analysis experiment, metabolites and enzyme activity detection kit experiment and Western blot. RESULTS Obtained from the TCMSP database, the five active ingredients in Sparganii Rhizome, corresponding to a total of 70 targets, constructed a PPI network with disease targets and further screened to obtain a key network composed of 86 core targets. The results of enrichment analysis of the KEGG signaling pathway showed that Sparganii Rhizome treatment of melanoma mainly involved metabolic-related pathways, p53 signal pathways, AMPK signal pathways, MAPK signal pathways, PI3K/Akt signal pathways, apoptosis signal pathways, etc. The results of in vitro experiments showed that the Sparganii Rhizome extract (SLTQW) inhibits the proliferation of melanoma A375 cells in a dose-depentent manner and reduces the rate of extracellular acidification of cells and the production of glycolytic metabolites pyruvate, lactic acid, ATP. The results of the kit and Western blot showed that the SLTQW inhibited the activity of PK and reduced the protein expression levels of PKM2, LDHA, MCT4. CONCLUSION SLTQW has obvious anti-melanoma effect, and its mechanism may be related to inhibiting the glycolysis-related proteins PKM2, LDHA, MCT4 expression and interfering with tumor cell glycolysis metabolism.

Identification of Aucklandia Costus, Dolomiaea Souliei and Inula Racemosa by PCR-RFLP Based on ITS Sequence

YAN Meng-yao, SONG Ping-shun, LAI Jing, GUO Ye-hong, NI Lin, ZHU Xi-chun

2022, 38(4): 339-346. doi: 10.14148/j.issn.1672-0482.2022.0339

[Abstract](221) [FullText HTML] (33) [PDF 4115KB](23)

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OBJECTIVE To establish a rapid method for distinguishing Aucklandia costus, Dolomiaea Souliei and Inula racemosa by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). METHODS The ITS gene sequences of Aucklandia costus, Dolomiaea souliei and Inula racemosa were compared, restriction enzymes were screened and identification primers were designed. The PCR amplification and digestion reaction conditions were optimized, and the methodological examinations and statistical analysis were carried out. RESULTS When the annealing temperature was 60 ℃ and the cycle number was 30, a single DNA band of 500~750 bp could be detected. When the substrate was 10 μL and the digestion time was 15 min, BsaHI enzyme could cut Aucklandia costus, Dolomiaea souliei and Inula racemosa into DNA bands of different sizes in a certain range. The results of methodology and statistics were good. CONCLUSION The PCR-RFLP method established in this study can accurately identify the three medicinal materials of Aucklandia costus, Dolomiaea souliei and Inula racemosa, avoid the mixed use of these three medicinal materials, and ensure the safety of the clinical medication.

Time Series Analysis of Stroke Syndromes and Related Medicines Based on Ancient Books of TCM

FU Xing, LI Qian-qian, YANG Feng, ZHOU Ran-ran, HOU Jian-chen, TANG Yang, TAO Xiao-hua

2022, 38(4): 347-354. doi: 10.14148/j.issn.1672-0482.2022.0347

[Abstract](214) [FullText HTML] (37) [PDF 3808KB](38)

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OBJECTIVE To investigate the syndrome-medicine rules of stroke prescriptions in the development of traditional Chinese medicine (TCM), to explore the relationships between stroke syndromes and related medicines according to the historical timeline, and to enrich the understanding of the syndrome-medicine relationships of stroke in ancient books of TCM. METHODS Considering the syndromes and related medicines in stroke prescriptions as research objects, time series similarity analysis was applied to screen stroke related prescriptions, and to extract syndromes and herbal medicines for obtaining standardized data. In addition, through programming our own R language, we calculated the morphological similarity distance (MSD) of syndromes and herbal medicines, and performed correlation and cluster analysis the MSD among syndromes, herbal medicines, and syndromes and herbal medicines, respectively. RESULTS The syndrome-syndrome correlation analysis in the time series of stroke syndromes and related medicines showed three syndrome clusters, including stroke, apoplectoid syndrome, and acute stroke. The intersection of Chinese herbal medicines showed that the core herbal group of strokes had been formed from Dynasty 600 A.D.(Kaihuang 20th year of Sui Dynasty). The syndrome-medicine correlation analysis yielded some syndrome-medicine relationships with significant correlation, suggesting the formation of three clusters of symptom-medicine. CONCLUSION The understanding of stroke in ancient books of TCM actually conceals three different perceptions of stroke, apoplectoid syndrome, and acute stroke, which is the meaning and value of excavating and studying ancient Chinese medical books with the help of scientific methods in today's scientific era. Thus, they deserve further attention.

Discussion on the Current Situation of Standard Evaluation of Traditional Chinese Medicine Formula Granules in Jiangsu Province

ZHOU Le, YANG Li-wei, SUN Jun

2022, 38(4): 355-360. doi: 10.14148/j.issn.1672-0482.2022.0355

[Abstract](511) [FullText HTML] (72) [PDF 1024KB](19)

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In recent years, the national and provincial drug regulatory departments have successively formulated and issued the standard of traditional Chinese medicine formula granules. According to incomplete statistics, by the end of March 2022, the national pharmacopoeia committee has successively issued the national standard of 201 varieties, and Jiangsu has successively issued the provincial standard of 206 varieties. This study summarizes the current situation of the standard review of traditional Chinese medicine formula granules in Jiangsu province from the aspects of medicinal materials/decoction pieces, standard decoction, production technology, quality standard and standard review, so as to provide guiding significance for the formulation of the standard of traditional Chinese medicine formula granules.

Research Progress on Chemical Constituents of Clerodendrum bungei Steud. and Its Pharmacological Activities

ZHAO He, CHENG Fei, QIN You, ZHANG Shui-han

2022, 38(4): 361-374. doi: 10.14148/j.issn.1672-0482.2022.0361

[Abstract](328) [FullText HTML] (172) [PDF 2134KB](40)

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Clerodendrum bungei Steud. is a plant of verbenaceae family, which is commonly used as folk herbal medicine. It has the effect of promoting blood circulation, disperses blood stasis, detoxification and detoxification. In this paper, the chemical constituents, pharmacological action and clinical application of Clerodendrum bungei Steud. were reviewed. It was concluded that Clerodendrum bungei Steud. contains phenylethanol glycosides, terpenoids, sterols and other chemical constituents. Clerodendrum bungei Steud. has a wide range of pharmacological effects, such as anti-tumor, analgesic, antibacterial and anti-inflammatory. Its clinical treatment of urticaria, cancer and improve menstrual irregularities. It provides reference for further research, development and utilization of Clerodendrum bungei Steud..

2022 Vol. 38, No. 4

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