Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α-MMP9-mediated HIF1α signaling pathway / 药学学报

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Bloodletting at auricular dorsal vein combined with auricular point sticking for menstrual migraine of qi stagnation and blood stasis and its effect on serum levels of E2 and 5-HT / 中国针灸

OBJECTIVE@#To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism.@*METHODS@#A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment.@*RESULTS@#Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05).@*CONCLUSION@#Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer / 中国中药杂志

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.

The level of mindfulness and fear of recurrence in patients after radical gastrectomy for gastric cancer: the chain mediating effect of illness uncertainty and negative coping styles / 中国实用护理杂志

Objective:To explore the relationship between the level of mindfulness, illness uncertainty, negative coping style and fear of recurrence in patients after radical resection of gastric cancer, and to understand the internal mechanism of how mindfulness affects the fear of recurrence.Methods:This was a cross sectional survey. From January 2019 to March 2021, the convenience sampling method was used to select 227 patients undergoing radical gastric cancer surgery in the Affiliated Hospital of Naval Medial University of Chinese PLA as the research objects. The general information questionnaire, Mindfulness Attention and Awareness Scale, Fear of Disease Progression Simplified Scale, Mishel′s Illness Uncertainty Scale and Simplified Coping Style Questionnaire were used for questionnaire surveys. The relationship between the level of mindfulness, illness uncertainty, negative coping style and fear of recurrence was explored and the model was tested.Results:The returned questionnaires were 207 with a recovery rate of 91.19%(207/227). Pearson correlation analysis showed that the level of mindfulness was negatively correlated with illness uncertainty, negative coping style, and fear of recurrence ( r=-0.176, -0.269, -0.480, all P<0.01). Illness uncertainty, negative coping styles were positively correlated with fear of recurrence ( r=0.433, 0.420, both P<0.01). The mediation model test showed that mindfulness had a significant direct effect on fear of relapse (effect value was -0.220), illness uncertainty and negative coping styles had significant partial mediating effect between mindfulness level and fear of recurrence (effect value were -0.036, -0.030). And the chain mediating effect of illness uncertainty and negative coping style was also significant (effect value was -0.006). Conclusions:The level of mindfulness can not only have a direct impact on the fear of recurrence in patients after radical gastrectomy, but also indirectly affect the fear of recurrence through the chain mediating effect of illness uncertainty, negative coping style, and disease uncertainty→negative coping style.

Research progress in the treatment of Alzheimer's disease by regulating brain-gut-microbiome axis with "Sanjiao" acupuncture method / 中华老年医学杂志

Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.

Therapeutic effect of retention enema with compound rhubarb decoction on a rat model of minimal hepatic encephalopathy based on bile acid metabolomics / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of rhubarb decoction （RD） retention enema on a rat model of minimal hepatic encephalopathy （MHE） and its mechanism of action based on bile acid （BA） metabolomics. MethodsA total of 55 male Sprague－Dawley rats were randomly divided into blank group （NC group with 10 rats）， hepatic encephalopathy group （HE group with 15 rats）， MHE group with 15 rats， and MHE+rhubarb decoction treatment group （MHEY group with 15 rats）. Intraperitoneal injection of carbon tetrachloride （CCl4） and thioacetamide （TAA） was performed to establish a rat model of MHE or HE， and the rats were sacrificed after 2 weeks of administration. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， total bilirubin （TBil）， and total bile acid （TBA） and the concentration of blood ammonia were measured； the colonic contents were collected to measure pH value； liver and brain tissue samples were collected， and HE staining was used to observe the histopathological changes of the liver； the bile was collected， and liquid chromatography－mass spectrometry was used to perform BA－targeted metabolomics analysis. Continuous data were expressed as mean±standard deviation； a one－way analysis of variance was used for comparison between multiple groups， and the least significant difference t－test was used for further comparison between two groups. ResultsCompared with the NC group， the HE group and the MHE group had a significant increase in searching platform latency （after modelling and after administration） and a significant reduction in the number of platform crossings （all P<0.05）； compared with the MHE group， the MHEY group had a significant reduction in searching platform latency （after administration） and a significant increase in the number of platform crossings， and the HE group had a significant increase in searching platform latency and a significant reduction in the number of platform crossings （all P<0.05）. Compared with the NC group， the HE group and the MHE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）； compared with the MHE group， the MHEY group had significant reductions in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）， and the HE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）. The MHE group had significantly lower TBA， primary BA， and secondary BA than the NC group （all P<0.05）； compared with the MHE group， the HE group had significantly lower TBA and primary BA （all P<0.05）， and the MHEY group had significantly higher TBA and primary BA （all P<0.05）. Compared with the NC group， the MHE group had significant reductions in GCDCA， GUDCA， GHDCA， TCDCA， TUDCA， GLCA， and TLCA （all P<0.05） and significant increases in γ－MCA， THCA， 7－KDCA， AlloLCA， and α－MCA （all P<0.05）， and compared with the MHE group， the MHEY group had significant increases in THDCA， TMCA， TCDCA， TUDCA， and TLCA （all P<0.05）. ConclusionRD retention enema can improve liver injury and cognitive function in a rat model of MHE induced by CCl4 and TAA by regulating the enterohepatic circulation of BA， possibly by increasing the synthesis of taurine－binding BA.

Research on dynamic on-line monitoring method of moisture attribute in three honey-processed Chinese herbal slice based on in-situ general model / 药学学报

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

Mechanism of Zhibai Dihuang decotion in treating postmenopausal osteoporosis / 药学学报

In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.

Herbal Textual Research on Gentianae Macrophyllae Radix in Famous Classical Formulas / 中国实验方剂学杂志

In this paper， through consulting relevant records in materia medica， medical and prescription books， and combining with modern literature， the name， origin， producing area， collection and processing of Gentianae Macrophyllae Radix in famous classical formulas from The Catalogue of Ancient Famous Classical Formulas （The First Batch） was systematically sorted out and textual research was carried out， in order to provide a basis for the development of the famous classical formulas containing Gentianae macrophyllae Radix. After textual research， it was found that Gentianae Macrophyllae Radix was the rectification of name in the past dynasties. In addition， there were other names such as Qinjiao， Qingua and Qinzhua. Gentiana macrophylla， G. straminea， G. dahurica and G. siphonantha were the main origin of this herb in ancient literature. Among them， G. macrophylla is the mainstream. In the Southern and Northern dynasties， G. straminea and G. macrophylla produced in northern Sichuan were recommended as the best. In the early Tang dynasty， G. macrophylla from the Liupan Mountain area at the border of Shanxi and Gansu provinces was the mainstream. During the Northern Song dynasty， G. siphonantha from Linxia and Qilian Mountain of Gansu province and G. macrophylla from eastern Shaanxi province were two new producing areas. In the Ming and Qing dynasties， the abundant base and production areas of Gentianae Macrophyllae Radix were gradually formed. In the past dynasties， harvesting was carried out in spring and autumn， and stored mainly by aeration drying or shade drying treatment. The processing methods are mainly the raw products after the net selection， cutting and drying， in addition to the frying， processing with wine and milk. G. macrophylla is recommended as the first choice for the herbal medicine involved in the famous classical formulas. Among them， wild products produced in Gansu and Shaanxi are the best， and raw products are recommended to be used. At the same time， it is suggested that G. siphonantha should be added to the subsequent edition of Chinese Pharmacopoeia as one of origins of Gentianae Macrophyllae Radix.

Rapid Identification of Gastrodiae Rhizoma with Different Sulfur Fumigation Levels Based on Ultra-fast Gas Phase Electronic Nose / 中国实验方剂学杂志

ObjectiveIn order to find a fast odor-based method for the identification of sulfur fumigated Gastrodiae Rhizoma， an ultra-fast gas phase electronic nose technology was used to identify the odors of different degrees of sulfur fumigated Gastrodiae Rhizoma decoction pieces. MethodHeracles NEO ultra-fast gas phase electronic nose was employed to collect gas chromatograms of unsulfured and sulfured with different degrees of Gastrodiae Rhizoma decoction pieces， gas chromatograms were performed under programmed temperature （initial temperature of 40 ℃， 0.2 ℃·s-1 to 60 ℃， and then 4 ℃·s-1 to 250 ℃）， the sample volume was 5 mL， the incubation temperature was 65 ℃ and incubation time was 35 min. Kovats retention index and the AroChemBase database were used for qualitative analysis， and stoichiometric analysis was performed on this basis. Principal component analysis （PCA）， discriminant factor analysis （DFA） and partial least squares-discriminant analysis （PLS-DA） models were established to identify the Gastrodiae Rhizoma decoction pieces with different degrees of sulfur fumigation. ResultAccording to the comparative analysis of AroChemBase database， there were significant differences in the odor characteristics of sulfur fumigated and non-sulfur fumigated Gastrodiae Rhizoma， cyclopentane， acetone and heptane might be the odor components to distinguish the degree of sulfur fumigation in Gastrodiae Rhizoma decoction pieces. The identification index of PCA model was 81， the accumulative discriminant index of the discriminating factors was 92.09% in DFA model， the supervisory model interpretation rate of PLS-DA model was 0.963 and the predictive ability parameter was 0.956， indicating that PCA， DFA and PLS-DA models could well distinguish Gastrodiae Rhizoma decoction pieces with different sulfur fumigation degrees. ConclusionHeracles NEO ultra-fast gas phase electronic nose can be used as a rapid method to identify and distinguish Gastrodiae Rhizoma decoction pieces with different levels of sulfur fumigation. Meanwhile， it can provide a rapid， simple and green method and technology for identification of traditional Chinese medicine decoction pieces by sulfur fumigation.

Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics / 中国中药杂志

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

The effect of Astragalus membranaceus (Fisch.) Bge. on intestinal function and gut microbiota homeostasis in aging mice / 药学学报

Aging can cause degenerative changes in the function of multiple tissues and organs in the body. Gastrointestinal diseases and intestinal dysfunction are very common in the elderly people. The purpose of this study is to explore the effect of the total extract of Astragalus membranaceus (Fisch.) Bge. on intestinal function and gut microbiota homeostasis in natural aging mice, which will provide clues for further mechanism study. The natural aging mice model is established and animal experiments follow the regulations of the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The overall health of the mice was evaluated by the "frailty index" scoring method. The intestinal absorption and transport function were measured by detecting intestinal glucose absorption capacity, transport time, lipase and amylase activities of aging mice. Intestinal inflammation was assessed by detecting inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the intestines of aging mice were tested by hematoxylin-eosin (H&E) staining and alizarin blue (AB) staining. The qRT-PCR method was used to explore the gene transcription level related with the proliferation and differentiation of intestinal stem cells. Microbiota analysis based on 16S rDNA were used to evaluate the composition of gut microbiota. The results showed that Astragalus had a tendency to reduce the "frailty index" of aging mice, but did not show a significant difference. In some indicators of aging phenotype, Astragalus has the most significant effect on hair loss and physical fitness. In terms of intestinal function, Astragalus could increase intestinal glucose absorption capacity, shorten intestinal transportation time and promote lipase secretion in aging mice. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-‍α) in the aging intestinal tissue were reduced after Astragalus administration. Astragalus also ameliorated the pathological degeneration of the intestinal tissue of aging mice by increasing the length of small intestinal villi, the thickness of colonic mucosa and goblet cell number. In addition, Astragalus elevated the expression of genes associated with the proliferation and differentiation in jejunum and modulated gut microbiota, especially restoring the abundance of Lachnospiraceae. Taken together, the above research results demonstrate the total extract of Astragalus as a key factor improving the intestinal function and gut microbiota homeostasis of aging mice.

Network pharmacology analysis to explore mechanism of Three Flower Tea against nonalcoholic fatty liver disease with experimental support using high-fat diet-induced rats / 中草药·英文版

Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein–protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

Effect of compound houttuynia mixture on influenza virus in vitro / 药学学报

Compound houttuynia mixture belongs to OTC class A medicine, which is made from Houttuynia cordata, Scutellaria baicalensis, Radix Isatidis, Forsythia, and Lonicera. As a kind of compound preparation of traditional Chinese medicine, houttuynia cordata mixture has extensive pharmacological effects, for example, clearing away heat and detoxifying, thus it is used for the sore throat, acute pharyngitis, and tonsillitis with wind-heat syndrome. In this study, the antiviral activity against influenza viruses and the primary mechanism of compound houttuynia mixture was evaluated. The antiviral effect of compound houttuynia mixture was determined by cytopathic effects (CPE), Western blot, quantitive reverse transcription PCR (qRT-PCR), and virus titer assays. The effect of houttuynia mixture on the replication cycle of influenza virus was evaluated by time-of-addition assay. In conclusion, the results showed that the compound houttuynia mixture had a broad-spectrum effect against influenza virus, including the international common influenza virus strains, the drug-resistant strains and the highly pathogenic avian influenza viruses H5N1 and H7N9. It mainly impairs the early stage of the viral replication.

Investigation of Host-guest Complexation Between 4-Sulfonylcalix 6 Arene and 15 Alkaloids from Traditional Chinese Medicines and Inhibitory Effect of Binding System on Proliferation of HepG2 and H9c2 Cells / 中国实验方剂学杂志

Objective:To investigate bonding ability between 4-sulfonylcalix ［6］ arene （SCA6） and 15 alkaloids （matrine， allomatrine， dauricine， daurisoline， quinidine， quinine， crotaline， vincristine， gelsemine， koumine， tetrandrine， aloperine， oxymatrine， sophocarpine and sinomenine）， and to evaluate viability<italic> in vitro</italic> of HepG2 and H9c2 cells with 12 alkaloids/SCA6 bonding systems （except allomatrine， oxymatrine， sinomenine）. Method:Fluorescence competitive titration was used to determine the binding constants of alkaloids and SCA6， the inhibitory effect of alkaloid/SCA6 complex on proliferation of HepG2 and H9c2 cells was investigated by cell counting kit-8 （CCK-8）. Result:All the 15 alkaloids had good bonding with SCA6 at the ratio of 1∶1 （the binding constants >1×10⁵ mol·L^-1， <italic>R</italic>²>0.98）， the aloperine （quinolizidine alkaloids） and SCA6 had the biggest binding constant （20.55×10⁶ mol·L^-1）. In addition to gelsemine， crotaline， matrine and sophocarpine， 8 alkaloids （including aloperine， tetrandrine， dauricine， daurisoline， quinidine， quinine， vincristine and koumine） exhibited significant anti-tumor effects on HepG2 cells. Except for daurisoline， the anti-proliferation effect of the other 11 alkaloids before and after binding with SCA6 had no difference in HepG2 cells. In addition to gelsemine， crotaline， matrine and sophocarpine， the anti-proliferation effect of the other 8 alkaloids before and after binding with SCA6 had no difference in H9c2 cells. Conclusion:SCA6 shows intense binding ability with bisbenzylisoquinoline， quinolizidine and indole alkaloids. It can improve the solubility of alkaloids without affecting their anti-tumor activity， which provides a reference for subsequent related applications of SCA6 as a drug delivery carrier.

An integrative metabolomics and network pharmacology method for exploring bioactive components and preliminary pharmacodynamics in medicinal parts of Harrisonia perforata / 中国中药杂志

In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.

Observation of therapeutic effect on coronavirus disease 2019 with insomnia in treatment with / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect on coronavirus disease 2019 (COVID-19) with insomnia between the combined treatment of @*METHODS@#A total of 90 patients with COVID-19 accompanied with insomnia were randomly divided into an observation group (45 cases, 3 cases dropped off) and a control group (45 cases). In the observation group, @*RESULTS@#After treatment, the scores of every item and the total scores in PSQI were all reduced as compared with those before treatment in the two groups (@*CONCLUSION@#The combined treatment of

Effects of Vitamin D Supplementation on Serum Lipid Profiles and Neonatal Outcomes in Gestational Diabetes Mellitus:a Meta-analysis / 中国医学科学院学报

Objective To evaluate the effects of vitamin D supplementation on serum lipid profiles and neonatal prognosis in gestational diabetes mellitus(GDM)patients.Methods The electronic databases including PubMed,Web of Science,Embase,CNKI,and Wanfang Data were searched from inception to February 1,2020.All randomized controlled trials that compared vitamin D supplementation with placebo or without supplementation for GDM women were included.Paper selection,data extraction,meta-analysis and sensitivity analysis were conducted independently by two authors.Risk of bias was assessed using the Cochrane Risk of Bias Tool.The data were analyzed in RevMan 5.3 software and Stata 12.0.Results Totally 17 randomized controlled trials involving 1432 patients(704 in the intervention group and 728 in the control group)were included in the meta-analysis.The results showed that vitamin D supplementation significantly reduced serum total cholesterol [MD=-6.11,95% CI=(-7.17,-5.04)],low-density lipoprotein cholesterol [MD=-10.80,95% CI=(-14.72,-6.89)],and triglyceride [MD=-8.11,95% CI=(-10.09,-6.13)],while significantly increased serum 25-hydroxyvitamin D3 level [MD=45.45,95% CI=(41.98,48.92)] and high-density lipoprotein cholesterol [MD=2.77,95% CI=(1.59,3.96)].In addition,vitamin D supplementation significantly reduced the incidence rate of hyperbilirubinemia [RR=0.49,95% CI=(0.35,0.68)],premature birth [RR=0.44,95% CI=(0.27,0.72)],and neonatal hospitalization [RR=0.44,95% CI=(0.29,0.67)].Conclusions Vitamin D supplementation may regulate the serum lipid profiles in patients with GDM and reduce the incidence of adverse neonatal outcomes.More high-quality RCTs are needed to confirm the findings in our study.

Research Progress of the Effects of Vitamin D Supplementation on Glycemic Control and Adverse Maternal-neonatal Outcomes in Gestational Diabetes Mellitus Patients / 中国医学科学院学报

Gestational diabetes mellitus(GDM)can cause blood glucose disorders in pregnant women and result in adverse maternal-neonatal outcomes.Vitamin D(VD)can improve glucose tolerance and insulin sensitivity,and thus theoretically,VD supplementation during pregnancy could improve glycemic control as well as maternal-neonatal outcomes in GDM patients.Although studies have shown that VD deficiency is associated with poor maternal-neonatal outcomes in GDM patients,no solid conclusion has been drawn with regard to the effects of VD supplementation on these patients.Therefore,here we summarized the research progress of the effects of VD supplementation on glycemic control and adverse maternal-neonatal outcomes in GDM patients,in an effort to guide the clinical VD supplementation during pregnancy.

Correlation study on non-volatile ingredients of Menthae Haplocalycis Herba formula granules and traditional herbal pieces by UPLC-MS/MS / 中国中药杂志

To establish the method for determining non-volatile ingredients of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isochlorogenic acid A, rosmarinic acid, ferulic acid, rutin, luteoloside, isoquercitrin, hesperidin, diosmin, diosmetin, luteolin, acacetin and linarin in Menthae Haplocalycis Herba formula granules and traditional herbal pieces by UPLC-MS/MS, and analyze the correlation of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces. Shim-pack GIST C_(18) column(2.1 mm×100 mm, 2 μm) was adopted with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution at the flow rate of 0.4 mL·min~(-1). The column temperature was set at 35 ℃. The quantitative analysis was performed using the electrospray ionization source and the multiple reaction monitoring. The linear relationship, resolution, repeatability and recovery of the 16 chemical components all met the requirements. The 16 non-volatile ingredients in traditional herbal pieces of Menthae Haplocalycis Herba could be tracked in formula granules. There were certain differences of the 16 chemical components among Menthae Haplocalycis Herba formula granules of different manufacturers and traditional herbal pieces of different producing areas. The UPLC-MS/MS method was simple, rapid and accurate, and could be used for the quality control of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces.