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1.
Article in English | WPRIM | ID: wpr-881073

ABSTRACT

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.


Subject(s)
Administration, Oral , Alkaloids/analysis , Animals , COVID-19 , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacokinetics , Flavonoids/analysis , Mice , SARS-CoV-2 , Saponins/analysis , Triterpenes/analysis
2.
Article in Chinese | WPRIM | ID: wpr-921786

ABSTRACT

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to investigate the metabolites of maackiain in rats based on the prediction function of UNIFI data processing system and liver microsomal incubation in vitro. Ten metabolites of maackiain after oral absorption were reasonably deduced and characterized. It was found that the biotransformation of maackiain mainly included phase Ⅰ oxidation, dehydrogenation, phase Ⅱ sulfate conjugation, glucosylation conjugation, and glucuronic acid conjugation. Among them, the product of glucosylation conjugation, trifolirhizin, was identified by comparison with the reference for the first time. Liver microsomal incubation in vitro further confirmed the metabolites and metabolic pathways of maackiain in rats. The metabolites in the blood, urine, and feces complemented each other, which revealed the migration, metabolism, and excretion modes of maackiain in rats. This study lays a foundation for the further investigation of the metabolic mechanism of maackiain in vivo and the in-depth research on the mechanism of pharmacodynamics and toxicity.


Subject(s)
Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Metabolic Networks and Pathways , Pterocarpans , Rats , Rats, Sprague-Dawley
3.
Article in Chinese | WPRIM | ID: wpr-828391

ABSTRACT

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.


Subject(s)
Animals , Bacteria , Classification , Chromatography, Liquid , Drugs, Chinese Herbal , Pharmacology , Gastrointestinal Microbiome , Metabolomics , Rats , Tandem Mass Spectrometry
4.
Acta Pharmaceutica Sinica ; (12): 82-88, 2019.
Article in Chinese | WPRIM | ID: wpr-778677

ABSTRACT

Natural products areone source of new drugs, and their target identification is pivotal forelucidating the mechanism of action. Most methods of target discovery and validation utilize labeling natural products with probes. This is time-consuming and laborious, and often results in activity decrease or change of the natural products. Recent methods withoutchemicalmodificationhave become the main force in the target identification of natural products, including direct or indirect methods. Direct methods are mainly based on the principle of affinity and stability of protein, and indirect methods infer the drug target from the change in physiological responses or biochemical signatures. This review summarizes recent methods for target identification and validation of label-freenatural products, providing new ideas and strategies for future research in natural products.

5.
Article in English | WPRIM | ID: wpr-776880

ABSTRACT

Traditional Chinese Medicine (TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease (CAD) who have not developed acute myocardial infarction (MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease. Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention. In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD.

6.
Acta Pharmaceutica Sinica ; (12): 709-715, 2018.
Article in Chinese | WPRIM | ID: wpr-779926

ABSTRACT

Primary hepatocellular carcinoma as the main pathological type of liver cancer is one of the common malignant tumors in our country. Liver cancer stem cells (LCSCs) have the characteristics of multidrug resistance, anti-radiotherapy and high tumorigenicity in addition to the characteristics of stem cells, namely, self-renewal, multi-directional differentiation and unlimited proliferation. Based on the above features, relapse and metastasis often occur after the patients being treated with conventional methods, which results in poor prognosis. Effective treatment targeting LCSCs has the potential to cure hepatocellular carcinoma (HCC) completely. This article reviews the common biomarkers used in identification of LCSCs and development of stem cell-targeted therapy for HCC.

7.
Acta Pharmaceutica Sinica ; (12): 425-431, 2018.
Article in Chinese | WPRIM | ID: wpr-779892

ABSTRACT

This study was aimed to explore the pharmacokinetics of epiberberine, jatrorrhizine, coptisine, palmatine, berberine of Jiaotai pill in the normal and depressed rats. According to ‘Katz’ method, the model of chronic unpredictable mild stress (CUMS) was established. The extract of Jiaotai pill was orally administered to rats, and the blood samples were collected via the the oculi chorioideae vein according to the time schedule. The concentrations of epiberberine, jatrorrhizine, coptisine, palmatine, berberine in rat plasma were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by DAS1.0 software. Compared with normal rats, the Cmax of palmatine, coptisine, berberine and jatrorrhizine in Jiaotai pill in depressed rats were 1.99, 2.14, 2.3, 1.82 times than the normal group, while the AUC0−t were 1.23, 1.25, 1.29, 1.46 times and the AUC0−∞ were 1.21, 1.25, 1.30, 1.43 times, which were significantly different.

8.
Article in Chinese | WPRIM | ID: wpr-776417

ABSTRACT

Application of a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, macroporous adsorbent resin, and reversed-phase HPLC, led to the isolation of 173 compounds including irdidoids, monoterpenes, sesquiterpenes, triterpenes, lignans, flavonoids, and simple aromatic derivatives from the ethyl acetate-soluble fraction of the whole plants of Valeriana jatamansi(Valerianaceae), and their structures were elucidated by spectroscopic methods including 1D, 2D NMR UV, IR, and MS techniques. Among them, 77 compounds were new. In previous reports, we have described the isolation, structure elucidation, and bioactivities of 68 new and 25 known compounds. As a consequence, we herein reported the isolation and structure elucidation of the remaining 9 new and 71 known compounds, the structure revision of valeriotriate A(8a), as well as cytotoxicity of some compounds.


Subject(s)
Acetates , Chromatography, High Pressure Liquid , Flavonoids , Iridoids , Lignans , Molecular Structure , Monoterpenes , Phytochemicals , Plant Extracts , Chemistry , Sesquiterpenes , Triterpenes , Valerian , Chemistry
9.
Article in Chinese | WPRIM | ID: wpr-776391

ABSTRACT

With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation. At the molecular level, traditional Chinese medicine is characterized by multi-component and multi-target prescriptions, which is expected to provide a reference for the development of multi-target drugs. This paper reviews the application of network biology in traditional Chinese medicine in six aspects, in expectation to provide a reference to the modernized study of traditional Chinese medicine.


Subject(s)
Drug Discovery , Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Systems Biology
10.
Article in Chinese | WPRIM | ID: wpr-775380

ABSTRACT

In this study, the specific primers and probes of Panax quinquefolius were designed for a quantitative real-time PCR, and the rapid identification method of P. quinquefolius was established by optimizing conditions. The method was used to validate 43 samples of the traditional Chinese medicine,and the results showed that 22 samples of P. quinquefolius were identified accurately. The limit of detection of the method can be reach to 1×10⁻⁴ ng. The method is accurate, fast, sensitive and specifically.


Subject(s)
DNA Primers , DNA Probes , Drugs, Chinese Herbal , Reference Standards , Panax , Genetics , Real-Time Polymerase Chain Reaction
11.
Article in Chinese | WPRIM | ID: wpr-664579

ABSTRACT

Aim To evaluate the effects of salvianolic acid B ( Sal B ) on bone metabolism and its potential mechanism in high fat diet ( HFD) mice.Methods Thirty C57BL/6J male mice were divided into three groups with 10 mice each, namely normal , HFD and HFD+Sal B.HFD and HFD+Sal B mice were treated with HFD, and HFD+Sal B group mice were also with Sal B (125 mg· kg -1· d-1).After 12 weeks' treat-ment, femurs were harvested .The effects of Sal B on biomechanical strength were evaluated by biomechani-cal tests, and the effects of Sal B on bone microstruc-ture were evaluated by Safranin O/fast green staining and hematoxylin and eosin staining .The expression of nuclear factor-kappa B ( NF-κB)-p65 and NADPH ox-idase 4 ( Nox4 ) and cathepsin K in femurs was deter-mined by immunohistochemical staining . Results Maximum load and elastic load significantly decreased ,and the trabeculae became thinner and irregular in the femurs of HFD mice , while Sal B treatment could re-verse the descending biomechanical strength and the disorganized femurs bone micro-structures in HFD mice.In addition, the expressions of Nox4, NF-κB-p65 and cathepsin Kmarkedly increased in HFD mice , and Sal B possessed the ability to down-regulate the ex-pression of Nox4, NF-κB-p65, and cathepsin K in the femurs triggered by HFD .Conclusions Sal B treat-ment improves bone metabolism via regulating Nox 4/NF-κB/cathepsin K signaling pathway in HFD mice . The findings contribute to the understanding and exten-sion of the applications of Salvia miltiorrhiza and its constituents on osteoporosis .

12.
Article in Chinese | WPRIM | ID: wpr-710165

ABSTRACT

AIM To establish an HPLC method for the simultaneous content determination of five constituents in Simotang Oral Liquid (Aucklandiae Radix,Aurantii Fructus,Arecae Semen,etc.).METHODS The analysis of 50% methanol extract of this drug was performed on a 35 ℃ thermostatic Agilent Zorbax C18 column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1% formic acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 283 nm.RESULTS Synephrine,norisoboldine,naringin,hesperidin and neohesperidin showed good linear relationships within the ranges of 5.8-185.6 μg/mL (r =0.999 9),0.829-26.52 μg/mL (r =1.000 0),9.775-312.8 μg/mL (r =1.000 0),0.594-19 μg/mL (r =0.999 5) and 5.2-166.4 μg/mL (r =1.000 0),whose average recoveries were 98.93%,98.95%,102.57%,99.67% and 103.43% with the RSDs of 1.85%,1.27%,0.52%,0.89% and 0.43%,respectively.CONCLUSION This simple,accurate and reproducible method can be used for the rapid quality control of Simotang Oral Liquid.

13.
Article in Chinese | WPRIM | ID: wpr-705283

ABSTRACT

Heart failure has become a global public health problem that seriously threatens human health. Due to "multi-target" effect, traditional Chinese medicine has unique advantages in the treat-ment of heart failure. Astragaloside Ⅳ is one of the main active ingredients of astragalus membrana-ceus.It has the functions of protecting the heart and neovascularization,anti-inflammation,anti-oxida-tion, regulating energy metabolism, neuroprotection and anti-cancer effects. This article reviews the recent progresses of astragaloside Ⅳ in the treatment of heart failure.Data show that astragaloside Ⅳcan inhibit heart fibrosis,attenuate excessively activation of renin-angiotensin system,increase energy metabolism, promote positive inotropic action, inhibit myocardial cell apoptosis, etc, which are all involved in the protective role of astragaloside Ⅳ in rodents or cellular models of heart failure.Astragalo-side Ⅳ may be a potential active ingredient in traditional Chinese medicine for the treatment of heart failure.

14.
Acta Pharmaceutica Sinica ; (12): 1262-1267, 2017.
Article in Chinese | WPRIM | ID: wpr-779721

ABSTRACT

This study was designed to investigate the synergistic analgesic effect between choline (Cho) and acetaminophen (Ace). Mice were treated with 0.6% acetic acid solution by intraperitoneal injection to build acetate writhing model. The KM mice were randomly divided into four groups:control group (n=10), Cho group (n=50), Ace group (n=50), combination group (Cho+Ace group, n=40), then the writhing times were counted respectively. OriginPro8.5 was used to calculate ED 50. The isobolographic analysis was used to test the interaction of Cho and Ace. To explore the mechanism, forty KM mice were randomly divided into control group, Cho group, Ace group and Cho + Ace group. Blood was collected for detection of TNF-α, IL-6, PGE2 and NF-κB content using ELISA kits. The result ED 50 was calculated as followings. ED50 of Cho and Ace was 19.47 mg·kg-1 and 20.56 mg·kg-1. The concentrations were 2.94 mg·kg-1 for Cho and 3.15 mg·kg-1 for Ace in the combination test. The levels of TNF-α, IL-6, PGE2 and NF-κB in Cho group and Ace group were lower than those in the control group (Pα, IL-6, PGE2, NF-κB in Cho + Ace group were reduced further (P< 0.05). The results revealed that Cho and Ace have synergistic analgesic effects, which may associate with inhibition of the NF-κB signaling pathway.

15.
Article in Chinese | WPRIM | ID: wpr-273716

ABSTRACT

<p><b>OBJECTIVE</b>To assess the effect of choline in ameliorating lipopolysaccharide (LPS)-induced central nervous system inflammation and cognitive deficits in mice and explore the underlying mechanism.</p><p><b>METHODS</b>Seventy-two mice were randomized into saline control group, LPS group, choline intervention group and choline control group. In the latter two groups, the mice received pretreatment with intraperitoneal injections of choline (40 mg/kg, 3 times daily for 3 consecutive days) prior to microinjection of LPS into the lateral cerebral ventricle to induce central nervous system inflammation; in saline and LPS groups, the mice were pretreated with saline in the same manner before intraventicular injection of artificial cerebrospinal fluid. Choline treatment was administered in the mice till the end of the experiment. The locomotor activity and spatial learning and memory capacity of the mice were examined. The expressions of Iba1 protein and proinflammatory cytokines (TNF-α and IL-β) I the hippocampal dentate gyrus, and the expressions of α 7nAchR, p38 MAPK and phosphorylated p38 MAPK in the hippocampus of the mice were detected.</p><p><b>RESULTS</b>Water maze test showed that compared with the saline control group, the mice in LPS group exhibited significantly reduced platform crossings (P<0.05), which was significantly increased by choline pretreatment (P<0.05). The mice pretreated with LPS expressed obviously increased levels of IBA-1 protein, TNF-α, and IL-1β in the hippocampus (P<0.01), and choline pretreatment significantly lowered the expressions of IBA-1 protein and IL-1β (P<0.05). The phosphorylation level of p38 MAPK increased significantly after LPS pretreatment (P<0.05), and was reduced by choline pretreatment (P<0.05); α 7nAchR expression increased significantly in choline intervention group as compared with that in the other 3 groups (P<0.05).</p><p><b>CONCLUSION</b>Choline can probably antagonize LPS-induced hippocampal p38 MAPK phosphorylation in mice via the α 7nAchR signaling pathway to protective against LPS-induced neuroinflammation and cognitive impairment in mice.</p>

16.
Article in Chinese | WPRIM | ID: wpr-230976

ABSTRACT

Shexiang Baoxin pill(SBP) is widely used for treating coronary heart disease in clinic, with ginsenosides as its main effective component. This study was designed to investigate and compare the pharmacokinetic characteristics of five ginsenosides of five compounds after multiple oral administrations, ginseng extract(GE) and SBP in myocardial infarction rats. After intragastric administration to myocardial infarction rats, the plasma samples were analyzed by liquid chromatography tandem triple-quad mass spectrometry. The results showed that Cmax of five compounds in all groups were less than 200 μg•L⁻¹. Tmax of corresponding analytes between groups revealed that ginsenosides in both SBP and GE were absorbed faster than each of the five compounds, indicating that GE and compounds contain components promoting absorption of ginsenosides. The oral administration doses of ginsenosides in SBP were the least in all groups, but with the greatest AUC0-tand AUCINF, which indicated that ginsenosides in SBP had the best absorption in all groups after oral administration to myocardial infarction rats. This study also demonstrated that compound is the best form of traditional Chinese medicine.

17.
Acta Pharmaceutica Sinica ; (12): 843-2016.
Article in Chinese | WPRIM | ID: wpr-779246

ABSTRACT

The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.

18.
Article in Chinese | WPRIM | ID: wpr-256564

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the synergistic analgesic effect of choline and parecoxib sodium and study its mechanism.</p><p><b>METHODS</b>In male Kunming mice with acetic acid-induced writhing, the EDof choline and parecoxib sodium (administered via the tail vein at 2 h and 30 min before modeling, respectively) and their combined use were determined. In saline (control) group, EDcholine (C) group, EDparecoxib sodium (P) group, and 1/2EDcholine and parecoxib sodium (1/2[C+P]) group, blood samples were collected from the eyeball 10 min after intraperitoneal administration of acetic acid to detect the levels of IL-1, TNF-α, PGE2, NF-κB, and I-κB levels using ELISA kits.</p><p><b>RESULTS</b>In the acetic acid-induced writhing model, the EDof choline and parecoxib sodium was 8.64 and 6.33 mg/kg, and when combined, their ED50 was 2.13 and 1.56 mg/kg, respectively. The isobolograms of parecoxib sodium and choline showed that the measured EDof the two drugs combined was below the theoretical EDvalue (P<0.05) with a combination index (CI) of <0.9. Compared with the control group, C group, P group, and 1/2 (C+P) group all showed significantly lowered IL-1 and TNF-α levels (P<0.05), especially in 1/2 (C+P) group (P<0.05). PGE2 level was significantly lower in P group and 1/2 (C+P) group compared with the control group (P<0.05). NF-κB and I-κB levels were significantly lowered in C, P, and 1/2 (C+P) groups (P<0.05), and the reduction was the most obvious in 1/2 (C+P) group (P<0.05).</p><p><b>CONCLUSION</b>Choline and parecoxib sodium has a synergistic analgesic effect, and their interactions may involve the in vivo expression of NF-κB.</p>

19.
Article in Chinese | WPRIM | ID: wpr-250491

ABSTRACT

A large number and wide varieties of microorganisms colonize in the human gastrointestinal tract. They construct an intestinal microecological system in the intestinal environment. The intestinal symbiotic flora regulates a series of life actions, including digestion and absorption of nutrient, immune response, biological antagonism, and is closely associated with the occurrence and development of many diseases. Therefore, it is greatly essential for the host's health status to maintain the equilibrium of intestinal microecological environment. After effective compositions of traditional Chinese medicines are metabolized or biotransformed by human intestinal bacteria, their metabolites can be absorbed more easily, and can even decrease or increase toxicity and then exhibit significant different biological effects. Meanwhile, traditional Chinese medicines can also regulate the composition of the intestinal flora and protect the function of intestinal mucosal barrier to restore the homeostasis of intestinal microecology. The relevant literatures in recent 15 years about the interactive relationship between traditional Chinese medicines and gut microbiota have been collected in this review, in order to study the classification of gut microflora, the relationship between intestinal dysbacteriosis and diseases, the important roles of gut microflora in intestinal bacterial metabolism in effective ingredients of traditional Chinese medicines and bioactivities, as well as the modulation effects of Chinese medicine on intestinal dysbacteriosis. In addition, it also makes a future prospect for the research strategies to study the mechanism of action of traditional Chinese medicines based on multi-omics techniques.

20.
Article in Chinese | WPRIM | ID: wpr-273795

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the protective effects of dexmedetomidine (Dex) against glutamate-induced cytotoxicity in PC12 cells and its mechanism.</p><p><b>METHODS</b>PC12 cells were treated with varying concentrations of dexmedetomidine 1 h before exposure to a high concentration of glutamate. The cell viability was measured by MTT assay, and LDH release, MDA content and SOD activity were measured. The level of ROS was tested by DCFH-DA staining and flow cytometry. The level of intracellular Cawas detected by Fluo-8 staining and flow cytometry, and the mitochondrial membrane potential (MMP) was determined with JC-1 staining and flow cytometry.</p><p><b>RESULTS</b>Within the concentration range of 0.01 to 100 µmol/L, Dex dose-dependently protected PC12 cells against glutamate-induced cytotoxicity. Treatment with 100 µmol/L Dex significantly increased the cell viability to (86.6∓2.2)% of that of the control cells (P<0.01) and decreased LDH release to 1.4∓0.1 folds of the control level (P<0.01). In PC12 cells exposed to glutamate, Dex pretreatment significantly reduced MDA content (P<0.01), enhanced SOD activity (P<0.01), inhibited ROS overproduction (P<0.01), reduced intracellular Calevel (P<0.01) and maintained a stable MMP (P<0.01).</p><p><b>CONCLUSION</b>Dexmedetomidine can protect PC12 cells against glutamate-induced injury possibly in relation with its anti-oxidative activity, inhibitory effect on intracellular calcium overload and protective effect of the mitochondria.</p>


Subject(s)
Animals , Apoptosis , Calcium , Metabolism , Cell Survival , Dexmedetomidine , Pharmacology , Glutamic Acid , Membrane Potential, Mitochondrial , Mitochondria , Metabolism , PC12 Cells , Rats , Reactive Oxygen Species , Metabolism
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