Mechanism of Zhishi Xiebai Guizhitang in Treating AS Based on Regulation of Cholesterol Metabolism in Foam Cells by TRPA1 / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg-1） and simvastatin group （0.002 g·kg-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Effect of Chaihu Guizhitang on Triple-negative Breast Cancer Cells： Based on HIF-1α/VEGFA Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Chaihu Guizhitang on triple-negative breast cancer （TNBC） cells based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor A （VEGFA） signaling pathway. MethodTNBC xenograft model was established and the cells were randomized into model group， capecitabine group （0.2 mg·kg-1）， Chaihu Guizhitang low-dose group， medium-dose group， and high-dose group （10.62， 21.23， 42.46 g·kg-1）， with 10 mice in each group. After 21 days of medication， the content of tumor necrosis factor-α （TNF-α） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The expression of HIF-1α mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction （real-time PCR）. Immunohistochemistry （IHC） was employed to detect the expression of HIF-1α， TNF-α， and VEGFA in tumor tissues， and CD34 staining to examine the angiogenesis in tumor tissues. Microvessel density （MVD） was calculated， and the protein expression of HIF-1α， VEGFA， and epidermal growth factor receptor （EGFR） in tumor tissues was measured by Western blot. ResultCompared with the model group， the rest four groups showed low levels of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， VEGFA， and CD34 in cells， and MVD （P<0.05， P<0.01）， and low protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. Compared with capecitabine group， medium-dose and high-dose Chaihu Guizhitang decreased the level of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， and VEGFA in cells （P<0.01）， CD34 expression， MVD， and protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. ConclusionChaihu Guizhitang may inhibit the angiogenesis in TNBC cells by regulating the expression of HIF-1α/VEGFA signaling pathway， thus exerting anti-tumor effect.

Modern Pharmacological Effect of Zhishi Xiebai Guizhitang： A Review / 中国实验方剂学杂志

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B2 （TXB2）， prostacyclin I2（PGI2） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.

Mechanism of Zhishi Xiebai Guizhitang in Alleviating Myocardial Injury in Rats with Myocardial Infarction Based on TNF/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Zhishi Xiebai Guizhitang （ZXGT） on isoproterenol （ISO）-induced myocardial infarction （MI） in rats through the tumor necrosis factor/nuclear factor-κB （TNF/NF-κB） signaling pathway. MethodForty-eight SD rats were randomly divided into control group （blank）， model group， perindopril group （4 mg·kg-1）， ZXGT group （24.4 g·kg-1）， ZXGT +inhibitor group （ZXGT， 24.4 g·kg-1， TNF-α receptor inhibitor R7050， 5 mg·kg-1）， and an inhibitor group （R7050， 5 mg·kg-1）， with eight rats in each group. The rats in each group were orally administered with their respective drugs for 7 days. Additionally， in the ZXGT + inhibitor group and the inhibitor group， R7050 was injected intraperitoneally at a dose of 5 mg·kg-1 on the 6th and 7th days. Except for the control group， all other groups were given intraperitoneal injections of ISO for 2 consecutive days to induce MI in rats. On the 7th day of the experiment， the rats were anesthetized 30 min after ISO injection， and their electrocardiograms （ECGs） were recorded to observe ST-segment elevation. Small animal echocardiography was used to measure global longitudinal strain （GLS） and cardiac synchrony. Blood samples were collected from the abdominal aorta to measure the levels of serum cardiac troponin T （cTnT）， creatine kinase-MB （CK-MB）， lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β）. Histopathological changes in myocardial tissue were observed using hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） was used to detect the expression of TNF-α， NF-κB p65， and p-NF-κB p65 proteins in myocardial tissue. Western blot was performed to measure the expression of tumor necrosis factor receptor 1 （TNFR1）， tumor necrosis factor receptor-associated factor 2 （TRAF2）， transforming growth factor-beta-activated kinase 1 （TAK1）， NF-κB inhibitory protein alpha （IκBα）， phosphorylated （p）-IκBα， NF-κB p65， and p-NF-κB p65 proteins in myocardial tissue. ResultCompared with the control group， the model group showed significant ST segment elevation on the ECG （P<0.01）， increased GLS， and reduced cardiac synchrony on echocardiography （P<0.01）. Histopathological examination revealed extensive myocardial necrosis. Furthermore， the serum levels of cTnT， CK-MB， LDH， TNF-α， and IL-1β were significantly increased （P<0.01）， and the expression levels of TNF-α， TNFR1， TRAF2， TAK1， p-IκBα， and p-NF-κB p65 proteins in myocardial tissue were significantly elevated （P<0.01）， while the expression level of IκBα was significantly decreased （P<0.01）. Compared with the model group， the perindopril group， the ZXGT group， the ZXGT + inhibitor group， and the inhibitor group rats showed a significant reduction in ST-segment elevation on the ECG （P<0.05， P<0.01）， improvement in GLS and cardiac synchrony （P<0.05， P<0.01）， a decrease in the area of myocardial necrosis， and reduced serum levels of cTnT， CK-MB， LDH， TNF-α， and IL-1β （P<0.01）. Additionally， the ZXGT group， the ZXGT + inhibitor group， and the inhibitor group downregulated the increased TNF-α， TNFR1， TRAF2， TAK1， p-IκBα， and p-NF-κB p65 protein expression levels and upregulated IκBα expression levels in the myocardial tissue （P<0.05， P<0.01）. No significant differences were observed between the ZXGT group and the ZXGT + inhibitor group or the inhibitor group. ConclusionZXGT can protect against ISO-induced myocardial injury in rats and improve cardiac function， and its mechanism of action may be related to the regulation of the TNF/NF-κB signaling pathway.

Etiology and Pathogenesis of Guizhitang Syndrome Based on ″Transformation in Accord with Constitution″ Theory / 中国实验方剂学杂志

ObjectiveTo explore the etiology and pathogenesis of Guizhitang syndrome， clarify the related suspicious cases debated by doctors in the past dynasties， and provide references for the clinical application of Guizhitang. MethodUnder the guidance of the "transformation in accord with constitution" theory， the etiology and pathogenesis of Guizhitang syndrome were analyzed by comparing the relevant articles in the classics such as Treatise on Cold Damage （Shanghanlun） and Synopsis of the Golden Chamber （Jingui Yaolue）. ResultGuizhitang syndrome not only refers to the greater yang wind-invasion syndrome. Instead， it can be divided into two categories， i.e.， exogenous Guizhitang syndrome and miscellaneous Guizhitang syndrome. The basic etiology of exogenous Guizhitang syndrome is internal blood deficiency or yin deficiency after severe diarrhea， which is the physical basis， namely the internal cause， while the wind is the external cause that results in cold. The basic etiology of miscellaneous Guizhitang syndrome is the deficiency of blood and body fluid without the external cause. The pathogenesis of Guizhitang syndrome is neither weak nutrient Qi and defensive qi nor strong nutrient Qi but weak defensive Qi. It attributes to weak nutrient qi and strong defensive qi or disorder of defensive Qi. The essence of the pathogenesis of Guizhitang syndrome is not ″exterior deficiency″ but ″deficiency of nutrient Qi″. ″Floating Yang and weak Yin″ does not refer to the pathogenesis， but the pulse. Yang refers to the Cun pulse and Yin refers to the Chi pulse. ConclusionThe etiology and pathogenesis of Guizhitang syndrome are controversial among ancient and modern doctors and textbooks. Many physicians annotate this problem but few pay attention to the constitution basis. According to the ″transformation in accord with constitution″ theory， the constitution is the internal basis for the formation of diseases and syndromes. The formation of Guizhitang syndrome is underpinned by the inherent constitution. ″Transformation in accord with constitution″ theory is helpful to understand the formation mechanism of Guizhitang syndrome. A new understanding of the etiology and pathogenesis of Guizhitang syndrome based on the ″transformation in accord with constitution″ theory is helpful to reveal the use principle of Guizhitang by ZHANG Zhong-jing. The exploration of the formation mechanism of various syndromes of six-meridian diseases and miscellaneous diseases， as well as the original idea of ZHANG Zhong-jing's prescriptions from the ″transformation in accord with constitution″ theory can provide a new idea for the understanding of ZHANG Zhong-jing's theory.

Effect of Guizhitang on Atherosclerosis by Regulating Immune and Intestinal Flora / 中国实验方剂学杂志

Objective:To observe the effect of Guizhitang （GZT） on peripheral blood monocytes， intestinal flora and AS plaque formation of ApoE^-/- mice induced by Western diet （WD）. Method:In this study， 40 12-week-old homozygous female ApoE^-/- mice were randomly divided into chow diet （CD） group （ApoE^-/-+CD）， WD group （ApoE^-/-+WD）， GZT group （ApoE^-/-+WD+GZT， 7.83 g·kg^-1） and atorvastatin （Atr） group （ApoE^-/-+WD+Atr， 3.33 mg·kg^-1）. And 10 matched C57BL/6 mice were set as wild CD control group （C57BL/6+CD）. Except the CD group， the rest groups were given WD to induce models. Treatment groups were given Guizhitang or atorvastatin orally in addition to WD， while ApoE^-/-+CD and ApoE^-/-+WD model groups were treated with the same volume of double steam water at the same time. After 4 weeks of intervention， 5 mice in each group were selected to collect the eyeball blood samples. The levels of plasma lipids were detected by automatic biochemical analyzer， and the proportion of peripheral blood mononuclear cells and its subtypes， and the expression levels of surface receptors toll like receptor 4 （TLR4） and CD36 were detected by flow cytometry， the intestinal flora of mice was detected by 16S rDNA sequencing. The remaining 5 mice in each group were intervened for 12 weeks， and the aorta was taken to detect the formation of aortic plaque by oil red O staining. Result:After intervention for 4 week， compared with C57BL/6+CD group， the levels of plasma total cholesterol （TC） and low-density lipoprotein （LDL） levels in ApoE^-/-+CD and ApoE^-/-+WD groups were increased （<italic>P</italic><0.01）. ApoE^-/-+WD group showed increase in the proportion of monocytes， their inflammatory subtypes Ly6C^__， and TLR4 expression on monocyte surface in blood （<italic>P</italic><0.05）. ApoE^-/-+WD group induced the imbalance of intestinal flora， with increase of Firmicutes and decrease of Verrucomicrobia in ileum of ApoE^-/-mice. Compared with ApoE^-/-+WD group， there was no significant change in blood lipid level and monocyte proportion in ApoE^-/-+WD+GZT group， but with decrease in the proportion of Ly6C^__， increase in the proportion of anti-inflammatory subtype Ly6C^-， and decrease in the expression of TLR4 and CD36 on monocyte surface （P<0.05）. ApoE^-/-+WD+GZT group showed decrease of Firmicutes and increase of Bacteroidetes and Verrucomicrobia in ileum of ApoE^-/-mice. After 12 weeks of intervention， ApoE^-/-+WD group showed increase in the number and area of aortic plaques in ApoE^-/-mice. ApoE^-/-+WD+GZT group showed decrease of the area of aortic AS plaques. Conclusion:GZT can reduce the immune damage and imbalance of intestinal flora caused by WD， then inhibit the formation of AS plaque.

Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on Overactive Activation of Cardiac Sympathetic Nervous System in Salt-Sensitive Hypertensive Rats / 中国实验方剂学杂志

Objective:To explore the effect and mechanism of Guizhitang with different proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on overactive cardiac sympathetic nerves in salt-sensitive hypertensive rats. Method:Randomly divide the forty male 6-week-old salt-sensitive hypertensive rats into five groups： the normal control group， the model group， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶2 group，and the Cinnamomi Ramulus and Paeoniae Alba Radix 2∶1 group， each group has 8 animals， the normal control group was fed with low-salt feed， and the remaining four groups were fed with 8% high-salt feed. After 4 weeks of feeding， gastric feeding was started. Give both the normal control group and model group saline and the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group， the 1∶2 group，and the 2∶1 group， were given Guizhitang aqueous solution at 4.0， 5.5 and 5.5 g·kg-1， respectively. Continuous gavage intervention was held for 4 weeks. IITC multi-channel non-invasive sphygmomanometer was used to detect changes of systolic blood pressure before and after treatment in rats. Left ventricular anterior wall end-diastolic thickness （LVAWd） and interventricular septal diastolic thickness （IVSd） were detected by echocardiography. Hematoxylin-eosin（HE）staining and Masson staining were used to observe the myocardial morphological changes of rats in each group， Western blot was used to detect the expression of nerve growth factor （NGF）， growth-associated protein 43 （GAP43） and tyrosine hydroxylase （TH） protein. Result:After 4 weeks of intervention with Guizhitang， compared with the normal control group， the blood pressure， LVAWd and IVSd of the model group were significantly increased， and the expressions of NGF， TH and GAP43 protein were significantly increased （P<0.01）. HE and Masson staining results showed that the model group had myocardial cell edema， a large number of inflammatory cell infiltration， myocardial fiber hyperplasia and disordered arrangement， and a large amount of collagen deposition could be seen in the intercellular substance. Compared with model group， the systolic blood pressure of rats in each Guizhitang group increased slowly， and the expression of NGF， TH and GAP43 protein decreased （P<0.05，P<0.01），the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group has the best effect. The results of echocardiography shows that the 1∶1 Guishao group could reduce LVAWd and IVSd levels （P<0.05，P<0.01）， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶2 group could reduce IVSd level （P<0.05）， there was no statistical difference in LVAWd， there was no statistical difference in LVAWd and IVSd in 2∶1 group. In terms of myocardial morphology， each group of Guizhitang can reduce cell edema and inflammatory cell infiltration， reduce myocardial fiber hyperplasia and collagen deposition， and improve the disorder of myocardial fiber arrangement. Among them， the 1∶1 group has the best effect. Conclusion:Guizhitang can inhibit the overactive activation of cardiac sympathetic nervous system，reduce the extent of myocardial fibrosis， inflammatory infiltration and myocardial hypertrophy， and protect salt-sensitive hypertension rats， whose mechanism may be related to regulating the expression of heart NGF.Among them， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group is better than the 1∶2 and 2∶1 group in reducing myocardial fibrosis， inflammatory infiltration and myocardial hypertrophy.

Effect of Guizhitang with Different Proportions of Cinnamomi Ramulus and Paeoniae Alba Radix in Regulating TGF-β1/Smads Signaling Pathway and Chronic Inflammation and Alleviating Myocardial Fibrosis in Salt-sensitive Hypertensive Rats / 中国实验方剂学杂志

<b>Objective::To observe the effect of Guizhitang with different proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on the expressions of transforming growth factor-<italic>β</italic>₁(TGF-<italic>β</italic>₁)/Smads signaling pathway and interleukin-10(IL-10), IL-6 and tumour necrosis factor-<italic>α</italic>(TNF-<italic>α</italic>)related inflammatory cytokines in salt-sensitive hypertensive rats, in order to explore the mechanism of Guizhitang in improving myocardial fibrosis in salt-sensitive hypertensive rats. <b>Method::Totally 40 male 6-week-old salt-sensitive rats were randomly divided into 5 groups: the normal control group, the model group, the 1∶1(RC/peony)Guishao group, the 1∶2 Guishao group, and the 2∶1 Guishao group, with 8 in each group. The normal control group was fed with normal salt diet, while the other four groups were fed with high-salt diet. After 4 weeks of feeding, the rats were given intragastric administration, the normal control group and the model group were given the same amount of normal saline, and the 1∶1 Guishao group, the 1∶2 Guishao group and the 2∶1 Guishao group were given 4.0, 5.5, 5.5 g·kg^-1 of Guizhitang by gavage for 4 weeks. Blood pressure was measured once a week, left ventricular end systolic diameter(LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening fraction (LVFS) were detected by using echocardiogram. The pathological changes of myocardial morphology were observed by htoxylin eosin(HE)and Masson staining. The expressions of type Ⅰ and Ⅲ collagen in myocardial tissue of each group was detected by immunohistochemistry. The mRNA expression levels of IL-10, IL-6 and TNF-<italic>α</italic> in myocardial tissue of each group were detected by quantitative real-time fluorescence polymerase chain reaction(Real-time PCR). The protein expression levels of TGF-<italic>β</italic>₁, <italic>α</italic>-smooth muscle actin(<italic>α</italic>-SMA), Smad2, Smad3 and Smad7 in myocardial tissue of each group were detected by Western blot. <b>Result::Compared with the normal control group, the blood pressure was increased in the model group at 8-15 weeks, LVESD, LVEDD were increased in the model group, while LVFS, LVEF were decreased in the model group. The collagen volume fraction was increased, immunohistochemistry showed the expression levels of type Ⅰ and Ⅲ collagen were increased, mRNA expression levels of IL-10, IL-6 and TNF-<italic>α</italic> were increased, the protein expression levels of TGF-<italic>β</italic>₁, Smad2, Smad3 and <italic>α</italic>-SMA were increased, whereas the protein expression of Smad7 was decreased (<italic>P</italic><0.01). Compared with the model group, the blood pressure rise of each group of Guizhitang was delayed in 12-15 weeks, LVESD and LVEDD were decreased in Guizhitang group (<italic>P</italic><0.01), LVFS, LVEF were increased in Guizhitang group (<italic>P</italic><0.01), the collagen volume fraction was decreased in Guizhitang group (<italic>P</italic><0.01), and the expressions of type Ⅰ and Ⅲ collagen were decreased in Guizhitang group (<italic>P</italic><0.01). At the same time, the mRNA expression of IL-10 was increased in Guizhitang group (<italic>P</italic><0.05, <italic>P</italic><0.01), the mRNA expressions of IL-6 and TNF-<italic>α</italic> were decreased in Guizhitang group (<italic>P</italic><0.01), and the protein expressions of TGF-<italic>β</italic>₁, Smad2, Smad3 and <italic>α</italic>-SMA were decreased in Guizhitang group (<italic>P</italic><0.05, <italic>P</italic><0.01), and the protein expression of Smad7 was increased in Guizhitang group (<italic>P</italic><0.01). Compared with the 2∶1 Guishao group, the effect of the 1∶1 Guishao group in improving the above indicators was more obvious (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::Guizhitang with different proportions of Ramulus Cinnamomi and Poeny can alleviate the degree of myocardial fibrosis in salt-sensitive hypertensive rats. The mechanism may be related to the regulation of TGF-<italic>β</italic>₁/Smads signaling pathway and the reduction of inflammatory response. Besides, the 1∶1 Guishao group showed the optimal effect in reducing inflammation and improving myocardial fibrosis.

Clinical Research on Treatment of Acute Cerebral Infarction with ‘Sanjiao Regular Sequence Therapy’ / 中国实验方剂学杂志

Objective:To evaluate the clinical efficacy of Sanjiao Cidi therapy on acute cerebral infarction and its effect on levels of S100-β protein （S100-β）， tumor necrosis factor-α （TNF-α）， hypersensitive C-reactive protein （hs-CRP） and neuropeptide （NPY）. Method:One hundred and eighty patients were randomly divided into control group （90 cases） and observation group （90 cases） by random number table. Patients in control group got aspirin enteric-coated tablets， 100 mg/time， 1 time/day， edaravone injection （injected within 30 minutes） for 14 days， 30 mg/time， 2 times/day， simvastatin tablets， 20 mg/time， 1 time/day. In addition to the basic therapy of meloxicam tablets， patients in observation group were also treated with Sanjiao Cidi therapy. In the first step， patients got Guizhi therapy to dredge Zhongjiao and Shangjiao， 1 dose/day， for 8 days. In the second step， patients got Sini therapy to dredge Zhongjiao and Xiajiao， 1 dose/day， for 10 days. In the third step， patients got Tianjing Gubentherapy， 1 dose/day， for 10 days. The course of treatment was 4 weeks. Before the treatment， and at the first， second， third and fourth weeks after treatment， National Institutes of Health Stroke Scale （NIHSS） was scored. And before and after treatment， function scale of fuglmeyer （FMA）， ability of daily life activities （ADL）， mini-mental state examination （MMSE） and main symptoms of traditional Chinese medicine were scored. Comprehensive assessment of patient report outcome （PRO） was made. And levels of S100-β， hs-CRP， TNF-α and NPY were detected. And the incidence rate of pulmonary infection， urinary infection， skeletal myalgia， shoulder hand syndrome and shoulder subluxation of patients were recorded during hospitalization. Result:The clinical efficacy in observation group was better than that in control group （Z=2.141， P<0.05）. Scores of NIHSS in observation group were lower than those in control group at the first， second， third and fourth weeks after treatment （P<0.01）. Scores of upper limb， legs and the total scores from FMA were higher than those in control group （P<0.01）. Scores of the main symptoms of traditional Chinese medicine， symptoms， psychological and social scores， total scores of PRO， S100-β， hs-CRP， TNF-α and NPY were lower than those in the observation group （P<0.01）. And scores of ADL and MMSE were higher than those in control group （P<0.01）. Total incidence of complications in observation group was 27.27%（21/77）， which was lower than 46.15%（36/78） in control group （χ2=5.941， P<0.05）. Conclusion:In addition to conventional western medicine treatment， Sanjiao Cidi therapy can treat the patients with acute cerebral infarction， alleviate the degree of neurological deficit， improve the cognitive function， motor function of limbs and the ability of daily life， reduce the main symptoms of traditional Chinese medicine， the incidence of complications and the inflammatory response， protect the nerve cells， with a better clinical efficacy and comprehensive effect in patients than pure Western medicine.

Interpretation of Theory of Weiluo Tongxin and Its Potential Molecular Mechanism Based on Zhishi Xiebai Guizhitang / 中国实验方剂学杂志

The scientific interpretation of the connotation of traditional Chinese medicine （TCM） theory is an important part of the development of TCM. Combined ancient classic theories with modern science and technology is a new path for the innovative development of TCM theory. Based on this， taking Zhishi Xiebai Guizhitang as an example， the molecular mining technology of integrative pharmacology-based research platform of TCM V2.0 （TCMIP V2.0） was used to analyze the mechanism of Zhishi Xiebai Guizhitang in preventing and treating gastropathic stomachache. A total of 220 chemical components in Zhishi Xiebai Guizhitang were obtained， and 674 targets were involved， of which 12 core targets directly affected angina pectoris and gastroesophageal reflux disease， including insulin （INS）， glyceraldehyde-3-phosphate dehydrogenase （GAPDH）， RAC-α serine/threonine-protein kinase 1 （AKT1）， tumour protein p53 （TP53）， albumin （Alb）， mitogen-activated protein kinase 3 （MAPK3）， interleukin-6 （IL-6）， etc. And tumor necrosis factor （TNF） signaling pathway， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， IL-17 signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway and other 121 pathways involved in these related diseases. All of these are the biological basis of Weiluo Tongxin theory. Combing the classical theories of TCM combined with the exploring the molecular mechanism of representative prescriptions can provide a demonstration and reference for the scientific connotation research of TCM theory.

Appreciation of Children Long-term Fever Diseases Case with Warm Therapy / 浙江中医药大学学报

[Objective]Discussing the clinical experiences in children long-term fever diseases case with warm therapy.[Methods]Collecting,organizing and analyzing the cases on children long-term fever diseases with warm therapy in our department.By analyzing the Renshen Baidu San case,Guizhi Tang case,Guizhi Reushen Tang case,Fuzi Lizhong tang case,Sinitang case,to expound thoughts of diagnosising and syndrome differentiation in treating children long-term fever diseases with warm therapy.[Results]For the five cases which were caused by suffering cold-evil or who were yang-deficiency,such as deficient person contracted by external cold,wind-stroke syndrome of Taiyang channel,Taiyang-Taiyin combination disease,Taiyin-Shaoyin combination disease,Shaoyin syndrome,using relieving methods such as superficies syndrome with pungent and warm natured drugs,tonifying and strengthening the body qi,sweating and releasing the exterior,regulating ying and wei,warming the middle and relieving exterior syndrome,warming and tonifying the spleen and kidney,and restoring yang to rescue from counter flow,and prescribe the prescription such as BaiDuSan,Guizhitang,GuiZhi RenShen Tang,FuZi LiZhongTang,SiNi Tang,often obtain a better curative effect.[Conclusion]Applying the thoughts of the six-meridian syndrome-differentiation,using the warm-methods to treat children long-term fever caused by cold syndrome,acquired a good effect,deserving promotion in clinic in further.