Direct infusion-multiple reaction monitoring cubed (DI-MRM3) enables widely targeted bi-omics of Colla Corii Asini (Chinese name: Ejiao).

Food authenticity is extremely important and widely targeted bi-omics is a promising pipeline attributing to incorporating metabolomics and peptidomics. Colla Corii Asini (CCA, Ejiao) is one of the most popular tonic edible materials, with counterfeit and adulterated products being widespread. An attempt was devoted to develop a high-throughput and reliable DI-MRM3 program facilitating widely targeted bi-omics of CCA. Firstly, predictive MRM program captured metabolites and peptides in trypsin-digestive gelatins. After data alignment and structure annotation, primary parameters such as Q1 â†’ Q3 â†’ QLIT, CE, and EE were optimized for all 17 metabolites and 34 peptides by online ER-MS. Though a single run merely consumed 6.5 min, great selectivity was reached for each analyte. Statistical results showed that nine peptides contributed to distinguish CCA from other gelatins. After cross-validation with LC-MRM, DI-MRM3 was justified to be reproducible and high-throughput for widely targeted bi-omics of CCA, suggesting a meaningful tool for food authenticity.

UPLC-Q-TOF-MS and UPLC-QQQ-MS were used for the qualitative and quantitative analysis of oligosaccharides in Fufang Ejiao Syrup.

Fufang Ejiao Syrup (FES) is a syrup made from Colla Corii Asini (CCA) and four botanicals (Codonopsis Radix (CR), Ginseng Radix et Rhizoma Rubra (GRRR), Rehmanniae Radix Praeparata (RRP) and Crataegi Fructus (CF)) as a result of modern processing and refining technology. FES has a lengthy history and is frequently used in clinical practice. Modern pharmacological studies have confirmed that oligosaccharides in any of the main medicinal herbs of FES, such as CR, GRRR, and RRP, have significant immune-enhancing effects. Therefore, the oligosaccharide component in FES could be its important pharmacologic substance, however, no studies on the content, structural analysis and source attribution of oligosaccharides in FES have been reported. The objective of this study is to systematically analyze the oligosaccharide in FES, compare the differences of the major oligosaccharides in different batches of FES produced by one manufacturer, and construct the content determination method for determining the content of the major oligosaccharides in FES, to provide technical support for FES quality assessment. This analysis revealed that a total of 13 oligosaccharides were identified from the FES, including 3 disaccharides, 4 trisaccharides, 3 tetrasaccharides, and 3 pentasaccharides. The constructed UPLC-QQQ-MS fingerprint of FES oligosaccharide is simple, stable, and reproducible, making it a useful tool for assessing FES's quality. There was a significant difference between the oligosaccharide fingerprints of 16 batches of FES,the results of fingerprint analysis combined with the statistical analysis suggested that the differences in stachyose, sucrose and raffinose contents in FES may be the reason for the great variations in oligosaccharide fingerprints of different batches of FES. For the 5 oligosaccharides in FES, the UPLC-QQQ-MS technique showed significant linearity in the linear range, along with good stability, repeatability, and recovery. Mannotriose was found to be higher in FES, followed by sucrose and stachyose, while kestose and raffinose were relatively lower. The results of this study reveal that oligosaccharides are important components of FES, and the method of fingerprinting and content determination constructed has strong practical value and is expected to be used for FES quality control.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

Application of ZHANG Zhongjing，s Jizihuang （Egg Yolk） Prescriptions in Type 2 Diabetes Mellitus based on the Theory of “Yin Restricts Fire” and “Many Different Diseases can be Treated in the Same Way” / 中医杂志

Type 2 diabetes mellitus （T2DM） can be categorized into “xiao ke （消渴）” in traditional Chinese medicine （TCM）. The theory of “yin restricts fire” originates from Inner Canon of Yellow Emperor （《黄帝内经》） which states that “yin essence restricts chief fire”， and the crucial pathogenesis and treatment of xiao ke coincide with this theory. ZHANG Zhongjing，s three prescriptions of Jizizhuang （egg yolk） are Baihe Jizizi Decoction （百合鸡子汤）， Huanglian Ejiao Decoction （黄连阿胶汤） and Painong Powder （排脓散）， which are scattered in different chapters of Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）. By analyzing and summarizing the mechanism and characteristics of the three prescriptions， it is found that the three prescriptions are in line with the characteristics of “yin restricts fire” and the pathogenesis of T2DM. These three prescriptions are composed of Jizizhuang and different medicinals. Baihe Jizizi Decoction is composed of Jizizhuang and Baihe （Bulbus Lilii）， and can be used to treat T2DM and mental diseases. Huanglian Ejiao Decoction is composed of Jizihuang， Ejiao （Colla Corii Asini）， Shaoyao （Radix Paeoniae Alba seu Rubra）， Huanglian （Rhizoma Coptidis） and Huangqin （Radix Scutellariae）， which could be used to treat T2DM and cardiorenal system diseases. Painong Powder is composed of Jizizhuang， Shaoyao， Jiegeng （Radix Platycodonis） and Zhishi （Fructus Aurantii Immaturus）， which can be used to treat T2DM and carbuncle. Therefore， based on the theory of “yin restricts fire” and “many different diseases can be treated in the same wa”， this paper propose that the three Jizihuang prescriptions could be used in T2DM， which could provide ideas for clinical treatment.

Mechanism and Molecular Targets of Ejiao Siwu Decoction for Treating Primary Immune Thrombocytopenia Based on High-Performance Liquid Chromatograph, Network Pharmacology, Molecular Docking and Cytokines Validation.

We explored the mechanisms and molecular targets of Ejiao Siwu Decoction (EJSW) for treating primary immune thrombocytopenia (ITP) using network pharmacology and molecular docking. Active compounds of EJSW were identified by high-performance liquid chromatography-diode array detector (HPLC-DAD) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) and their targets were obtained from HERB and SwissTargetPrediction, and ITP targets were obtained from Comparative Toxicogenomics Database (CTD) and GeneCards. STRING and Cytoscape were used for protein-protein interaction (PPI) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses by WebGestalt yielded a gene-pathway network, Autodock molecular docking was applied to screen targets and active compounds, and cytokines were detected using a cytometric bead array (CBA) human inflammation kit. We identified 14 compounds and 129 targets, and 1,726 ITP targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumour necrosis factor (TNF), interleukin-6 (IL6), caspase-3 (CASP3) and tumour suppressor protein (TP53) were core targets (nodes and edges). Functional annotation identified cofactor binding and coenzyme binding, and 20 significantly enriched pathways. Active compounds of EJSW were successfully docked with ITP targets. Tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) were upregulated in ITP patients, vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor D (VEGF-D) were downregulated, and EJSW treatment reversed these trends. EJSW may regulate key ITP targets based on the in silico analyses, and protect vascular integrity through AGE-RAGE signalling, complement and coagulation cascades, and VEGF signalling by downregulating TNF-α, IL-1ß and other inflammatory factors.

Qualitative and Quantitative Analysis of Ejiao-Related Animal Gelatins through Peptide Markers Using LC-QTOF-MS/MS and Scheduled Multiple Reaction Monitoring (MRM) by LC-QQQ-MS/MS.

Donkey-hide gelatin, also called Ejiao (colla corii asini), is commonly used as a food health supplement and valuable Chinese medicine. Its growing popular demand and short supply make it a target for fraud, and many other animal gelatins can be found as adulterants. Authentication remains a quality concern. Peptide markers were developed by searching the protein database. However, donkeys and horses share the same database, and there is no specific marker for donkeys. Here, solutions are sought following a database-independent strategy. The peptide profiles of authentic samples of different animal gelatins were compared using LC-QTOF-MS/MS. Fourteen specific markers, including four donkey-specific, one horse-specific, three cattle-specific, and six pig-specific peptides, were successfully found. As these donkey-specific peptides are not included in the current proteomics database, their sequences were determined by de novo sequencing. A quantitative LC-QQQ multiple reaction monitoring (MRM) method was further developed to achieve highly sensitive and selective analysis. The specificity and applicability of these markers were confirmed by testing multiple authentic samples and 110 batches of commercial Ejiao products, 57 of which were found to be unqualified. These results suggest that these markers are specific and accurate for authentication purposes.

Ejiao ameliorates lipopolysaccharide-induced pulmonary inflammation via inhibition of NFκB regulating NLRP3 inflammasome and mitochondrial ROS.

There is no effective treatment for acute lung injury (ALI) at present. Some studies have reported the anti-inflammatory effect of Ejiao, but no study has addressed the underlying action mechanism. In this study, the CCK8 assay displayed Ejiao had a protective effect against LPS-elicited inflammatory lung epithelial Beas 2B cells (LILEB 2B cells). Beas 2B cells treated with LPS and Ejiao were challenged with NFκB inhibitor Bay11-7082 and ROS scavenger N-acetyl cysteine (NAC) alone and in combination. The results of qRT-PCR, Western blotting and fluorescence labeling experiments using Bay11-7082 and NAC demonstrated Ejiao could significantly decrease the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1ß related to pyroptosis of LILEB 2B cells. Moreover, Ejiao reduced the production of mitochondrial ROS and reversed the change of mitochondrial membrane potential of LILEB 2B cells. Then, HE staining demonstrated Ejiao had a protective effect against the LPS-elicited ALI mouse model (LAMM). Ejiao also dramatically decreased the cell amount and the overall protein concentration of bronchoalveolar lavage fluid in LAMM. Immunohistochemical staining showed Ejiao remarkably reduced the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1ß. The ELISA of IL-1ß revealed Ejiao could dose-dependably decrease the concentration of IL-1ß in lung tissues, serum and BALF of LAMM. Finally, fluorescence labeling demonstrated Ejiao significantly reduced the mitochondrial ROS generation in the lung tissue of LAMM. This finding may afford a novel strategy for the precaution and therapy of ALI.

Donkey Skin Trade and Its Non-compliance With Legislative Framework.

Donkeys (Equus asinus) are facing a global crisis. Their welfare, and even survival, is being compromised as the demand for their skins increases. This demand is driven by the need to supply raw materials to produce ejiao, a Traditional Chinese Medicine made from collagen extracted from donkey skins. Since there is no productive chain for donkey skin production outside of China, the global trade is an entirely extractive industry that has resulted in the decimation of some local donkey populations. The donkey skin trade is demonstrably unsustainable, from the ethical issues associated with poor welfare, to the biosecurity and human health risks the trade poses; and it violates both legal frameworks and moral expectations at both a national and global level.

Efficacy and Safety of Ejiao (Asini Corii Colla) in Women With Blood Deficient Symptoms: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

Equus asinus L [Equidae; Asini Corii Colla] (donkey-hide gelatin, Ejiao), a well-known traditional Chinese medicine, has been widely used to nourish the blood, especially for women. The aim of this study was to assess the efficacy and safety of Ejiao in blood-deficient patients. A total of 210 participants were recruited and randomly allocated into the placebo control group and Ejiao-treated group (6 g/day). The primary outcomes on the efficacy of Ejiao included traditional Chinese medicine symptom scores, blood indicators, and SF-36. The secondary outcomes were changes in fireness and safety evaluation. Results showed that Ejiao treatment for 8 weeks had significantly improved dizziness symptoms. Among the tested 24 blood biochemical parameters, the hematocrit and red blood cell numbers decreased in the placebo control group, but decreased significantly less in the Ejiao treatment group. The white blood cell and neutrophil counts increased in the Ejiao group but were within the normal range. In addition, the quality of life improved as the scores in SF-36 domains were significantly higher in the Ejiao group. At the same time, there was no significant change in the fire-heat symptoms score or other safety parameters. Considering all these, our study showed that Ejiao has a promising effect in women suffering from blood deficiency without obvious adverse effects.

Efficacy of Chinese herbal prescriptions containing Ejiao or Velvet antler for management of uterine fibroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of the controversial Chinese herbal prescriptions containing Ejiao or Velvet antler (VA) in the treatment of uterine fibroids. METHODS: We searched 4 famous Chinese databases, the Chinese Clinical Trial Registry, PubMed, Cochrane Central, Google Scholar, Embase, and J-STAGE up to July 2019. We included all eligible randomized controlled trials (RCTs) which compared Chinese herbal prescriptions containing Ejiao or VA (E/VA) with placebo, pharmaceutical intervention, surgery, or other traditional Chinese medicines (TCMs) for uterine fibroids and assessed the risk of bias according to the Cochrane Collaboration's tool. The software Review Manager (RevMan) 5.1 was used for data analysis. RESULTS: A total of 9 RCTs involving 844 patients were identified. Meta-analyses demonstrated that TCM (E/VA) plus mifepristone reduced the volume of uterine fibroids to a greater degree than mifepristone alone [standardized mean difference (SMD): 0.59, 95% CI: 0.33 to 0.85, P<0.00001, I2=50%]; TCM (E/VA) did not enlarge the volume of fibroids when menopausal hormone therapy (MHT) significantly increased the volume (SMD: 1.06, 95% CI: 0.73 to 1.38, P<0.00001, I2=0. The uterine volume change difference was larger via combination therapy of TCM (E/VA) and mifepristone than that of mifepristone (SMD: 0.29, 95% CI: 0.09 to 0.49, P=0.005, I2=0%). The TCM (E/VA) group of had an advantage over the control group in the improvement of fibroid-related symptoms [relative risk (RR): 1.24, 95% CI: 1.15 to 1.35, P<0.00001, I2=0%]. It was found that TCM (E/VA) plus mifepristone could lower estradiol (E2) levels to a greater degree than mifepristone alone (SMD: 1.63, 95% CI: 0.42 to 2.83, P=0.008, I2=97%), as well as progesterone (P) level (SMD: 0.79, 95% CI: 0.55 to 1.04, P<0.00001, I2=43%) in non-menopausal women. A total of 5 studies reported adverse events (AEs), the TCM (E/VA) group was potentially safer than the control group, with lower incidence of AEs (RR: 0.24, 95% CI: 0.15 to 0.40, P<0.00001, I2=25.8%). DISCUSSION: TCM prescriptions containing E/VA seemed superior to the control group in shrinking the volume of uterine fibroids and uterus, improving related symptoms, and reducing non-menopausal women's E2 and P levels, with lower incidence of AEs.

[Huanglian Ejiao Decoction formula syndrome and its application for refractory insomnia].

Huanglian Ejiao Decoction,firstly recorded in Treatise on Febrile Diseases,could be used to treat heat-conversion syndrome of Shaoyin. It has been identified that,the indications of Huanglian Ejiao Decoction include:(1)in modern medicine,it can be used to treat insomnia,arrhythmia,oral ulcer,Xiali,blood syndrome and other diseases;(2)in terms of symptoms and signs,it is mainly used for restlessness,ritability,insomnia,extremely difficult to fall asleep,palpitation,atrial premature beat,ventricular premature beat and other arrhythmias,stomach distension and stuffiness,stomach pain,vomiting,abdominal pain,cramps,lower edge,constipation,blush,red lips,easy bleeding,red tongue,thin or no coating,dry tongue surface,or light red tongue,or dark red,thin white tongue coating,and rapid pulse. It has been also identified that,(1)although the original statement of Huanglian Ejiao Decoction is very simple,it can not only be used according to irritability and insomnia;(2)tongue image is not the key to syndrome differentiation of this prescription;(3)the essence of Shaoyin syndrome is not completely heart kidney Yang deficiency,which is closest to shock in modern medicine,including septic shock,hypovolemic shock and cardiogenic shock;(4)the essential difference between Shaoyin cold and heat conversion syndrome of Shaoyin lies in the different types of shock,in which cardiogenic shock is the main cold type,while septic shock is the main heat shock;(5)heat-conversion syndrome of Shaoyin is more common in the late stage of septic shock,and part of it can be seen in the stage of heart failure combined with sympathetic activation;(6)Dioscoreae Rhizoma and Rehmanniae Radix are often used to replace egg yolk;(7)Huanglian Ejiao Decoction takes effect quickly and the course of treatment is short.

Exploring the Safety, Effectiveness, and Cost-Effectiveness of a Chinese Patent Medicine (Fufang E'jiao Syrup) for Alleviating Cancer-Related Fatigue: A Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Multicenter Trial.

OBJECTIVE: To provide higher level evidence on the benefits of a Chinese patent medicine (CPM) (Fufang E'jiao Syrup, FFEJS) for alleviating cancer-related fatigue (CRF), this article describes a protocol for a randomized controlled trial. METHODS/DESIGN: We designed a double-blind, placebo-controlled stratified permuted block randomization clinical trial on CRF among 3 types of cancer in China. Participants will be equally allocated to FFEJS group or placebo group according to the randomization sequence and the hospitals they were enrolled at. Each patient will receive 20 ml of either the study formula FFEJS or a placebo formula, 3 times a day for 6 weeks. The follow-up period will be another 4 weeks for safety evaluation. The primary outcome is the difference in improvement of fatigue as measured with the Revised Piper Fatigue Scale-Chinese Version (RPFS-CV). Secondary outcomes include change in fatigue (measured by routine blood panel and hormones in peripheral blood) and QoL (measured by Edmonton symptom assessment scale and Functional Assessment of Cancer Therapy). Patient safety will be measured by liver, renal or cardiac damage, and the risk of FFEJS having a tumor promotion and progression effect will be monitored throughout this study. Cost-effectiveness will also be evaluated mainly by incremental cost per each quality-adjusted life year gained. DISCUSSION: This article describes the study design of a CPM for CRF in patients with advanced cancer through exploring the effectiveness, safety, and cost-effectiveness of FFEJS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147312. Registered on 1 Sep 2019.

Endoparasites of donkeys (Equus asinus) used in commercial skin exploitation in the Northeast of Brazil / Endoparasitos de jumentos (Equus asinus) utilizados em uma exploração comercial de peles no Nordeste brasileiro

The present study identified the main endoparasites present in donkeys (Equus asinus) used in skin exploitation located in Cando municipality, Bahia State, Northeast of Brazil. The samples were collected from September 2019. Feces were collected from the rectal ampulla of 34 animals, macroscopically visualized for parasitic forms, and microscopically evaluated to identify endoparasites forms using the McMaster method. Parasitological results were associated with sex, age, and bodyweight Stata Corp LLC 14. Endoparasites were found in 82.3% of the animals, with the egg count ranging from 50 to 1050 eggs per gram (EPG). The sole presence of superfamily Trichostronglylidae was observed in 67.6% of the donkeys, in 8.8% co-infected by Trichostronglylidae and Eimeria spp., while Trichostronglylidae and Strongyloides westeriwas detected in 2.9%, and simultaneous infection by Trichostronglylidae, Strongyloides westeri, and Oxyuris equi was observed in 2.9%. The occurrence of parasitic infections varies according to nutritional status, age, sex, and environmental exposure (p>0.05). A high occurrence of infection was observed in young animals and those with lower body weight.(AU)

O presente trabalho identificou os principais endoparasitas em jumentos utilizados em uma exploração de pele localizada no município de Canudos, Estado da Bahia, Nordeste do Brasil. As amostras foram colhidas no período de setembro de 2019. Fezes de 34 jumentos, colhidas diretamente da ampola retal, foram visualizadas macroscopicamente para formas parasitárias e avaliadas microscopicamente para identificar endoparasitos pela técnica de McMaster. Os resultados parasitológicos foram associados com sexo, idade e peso corporal pelo Stata Corp LLC 14. Endoparasitas foram encontrados em 82,3% dos animais, com contagem de ovos variando de 50 a 1050 ovos por grama (OPG). Presença de unicamente parasitos da superfamília Trichostronglylidae foi observada em 67,6% dos jumentos, 8,8% estavam coinfectados por Trichostronglylidae e Eimeria spp., 2,9% por Trichostronglylidae e Strongyloides westeri e 2,9% apresentaram presença simultânea de Trichostronglylidae, Strongyloides westeri e Oxyuris equi. A ocorrência de infecções parasitárias varia de acordo com a idade, sexo e exposição ambiental (p>0.05). Observou-se alta ocorrência de animais infectados nos animais jovens e naqueles com menor peso corporal.(AU)

The reality of the donkey's exploitation for the hide trade in Brazil: disease outbreaks and animal welfare compromised in rescued donkeys / A realidade da exploração de jumentos para exportação de pele no Brasil: surtos sanitários e bem-estar animal comprometido em asininos resgatados

About 800 donkeys that were confined in a restrictive area used in a manner comparable to a warehouse for receiving donkeys for slaughter were abandoned. After receiving reports of mistreatment, civilians acted to save the animals. A task force was organized that planned veterinary and zootechnical actions and activities for daily health management, feeding, and clinical care to attend to the abandoned donkeys. Positive cases were diagnosed for glanders, equine infectious anemia, equine herpesvirus, and equine babesiosis. The objective of this communication is to bring to the attention of the scientific community the interventions in the area of animal health and welfare, to address the episode of northeast donkeys that were victims of international trade. It is fundamental to change the approach related to the management of donkeys in Brazil, and appeal to the necessity to identify ethical and sustainable ways to incorporate donkeys in Brazil in the 21st century.(AU)

Cerca de 800 jumentos confinados em uma área utilizada como entreposto de recebimento e encaminhamento de jumentos para abate foram abandonados. Após denúncias de maus tratos, a sociedade civil atuou para salvar os animais. Foi constituída uma força tarefa que planejou ações e atividades veterinárias e zootécnicas atuando diariamente no manejo sanitário, na alimentação e nos cuidados clínicos na assistência aos jumentos abandonados. Foram diagnosticados casos positivos de mormo, anemia infecciosa equina, herpesvírus equino e babesiose equina. O objetivo desta comunicação foi relatar para a comunidade científica as intervenções nas áreas de saúde e bem-estar animal no episódio dos jumentos nordestinos vítimas do comércio internacional. É fundamental mudar a abordagem em relação ao manejo de jumentos no Brasil e apelar para a necessidade de identificar maneiras éticas e sustentáveis de incorporar os jumentos no Brasil do século 21.(AU)

Huanglian Ejiao Decoction formula syndrome and its application for refractory insomnia / 中国中药杂志

Huanglian Ejiao Decoction,firstly recorded in Treatise on Febrile Diseases,could be used to treat heat-conversion syndrome of Shaoyin. It has been identified that,the indications of Huanglian Ejiao Decoction include:(1)in modern medicine,it can be used to treat insomnia,arrhythmia,oral ulcer,Xiali,blood syndrome and other diseases;(2)in terms of symptoms and signs,it is mainly used for restlessness,ritability,insomnia,extremely difficult to fall asleep,palpitation,atrial premature beat,ventricular premature beat and other arrhythmias,stomach distension and stuffiness,stomach pain,vomiting,abdominal pain,cramps,lower edge,constipation,blush,red lips,easy bleeding,red tongue,thin or no coating,dry tongue surface,or light red tongue,or dark red,thin white tongue coating,and rapid pulse. It has been also identified that,(1)although the original statement of Huanglian Ejiao Decoction is very simple,it can not only be used according to irritability and insomnia;(2)tongue image is not the key to syndrome differentiation of this prescription;(3)the essence of Shaoyin syndrome is not completely heart kidney Yang deficiency,which is closest to shock in modern medicine,including septic shock,hypovolemic shock and cardiogenic shock;(4)the essential difference between Shaoyin cold and heat conversion syndrome of Shaoyin lies in the different types of shock,in which cardiogenic shock is the main cold type,while septic shock is the main heat shock;(5)heat-conversion syndrome of Shaoyin is more common in the late stage of septic shock,and part of it can be seen in the stage of heart failure combined with sympathetic activation;(6)Dioscoreae Rhizoma and Rehmanniae Radix are often used to replace egg yolk;(7)Huanglian Ejiao Decoction takes effect quickly and the course of treatment is short.

[Herbalogical study of Colla Corii Asini(Ejiao)].

Colla Corii Asini(Ejiao)is an important Chinese medicine used in China for thousands of years, and is well known for its famous tonic properties. The herbalogical study was detailed carried out based on the naming, habitat, harvesting, processing, medicinal properties and clinical efficacy. The results showed that the name of Ejiao could be traced back to Shennong's Materia Medica, and various names of Lvpi Jiao, Penfu Jiao and Fuzhi Jiao were recorded in other ancient books. In the many intervening centuries, the main materials of Ejiao had been replaced from cow leather before Tang Dynasty to donkey skin in the middle to late Tang Dynasty. This phenomenon could be probably caused by complicated social factors of various periods and different efficacy of Ejiao made by all kinds of raw materials. Ejiao was merely processed with the simple methods before Tang Dynasty, which subsequently improved avariety of methods to enhance the supplementation action. Most importantly, Ejiao has a wide clinic application along with the development of processing theories and methods, which can be found in various Classics, especially in imperial medical case record in Qing Dynasty.

The Potential for New Donkey Farming Systems to Supply the Growing Demand for Hides.

The demand for donkey hides for ejiao, a Traditional Chinese Medicine, has resulted in rapidly increasing prices for donkey hides and donkeys. This has put pressure on donkey populations globally and has implications for donkey welfare and the livelihoods of those who rely on donkeys as working animals. The aim of the research was to explore the feasibility of setting up new donkey farming systems to supply the rising demand for ejiao using a system dynamics model of donkey production. Results show that the size of the initial female breeding herd, reproductive performance, age of reproduction, percentage of female births and average breeding life of donkeys are key variables affecting the time to build up the donkey population to supply the demand for hides, which will be at least ten to fifteen years. The implications of this are: (i) prices for donkey hides will continue to increase, (ii) companies producing ejiao will use other ingredients, (iii) China will continue to source donkey hides from around the world, and (iv) there will be continued theft and illegal trade of donkeys and concerns for rural households reliant on donkeys for their livelihoods and adverse impacts on donkey welfare.

Herbalogical study of Colla Corii Asini(Ejiao) / 中国中药杂志

Colla Corii Asini(Ejiao)is an important Chinese medicine used in China for thousands of years, and is well known for its famous tonic properties. The herbalogical study was detailed carried out based on the naming, habitat, harvesting, processing, medicinal properties and clinical efficacy. The results showed that the name of Ejiao could be traced back to Shennong's Materia Medica, and various names of Lvpi Jiao, Penfu Jiao and Fuzhi Jiao were recorded in other ancient books. In the many intervening centuries, the main materials of Ejiao had been replaced from cow leather before Tang Dynasty to donkey skin in the middle to late Tang Dynasty. This phenomenon could be probably caused by complicated social factors of various periods and different efficacy of Ejiao made by all kinds of raw materials. Ejiao was merely processed with the simple methods before Tang Dynasty, which subsequently improved avariety of methods to enhance the supplementation action. Most importantly, Ejiao has a wide clinic application along with the development of processing theories and methods, which can be found in various Classics, especially in imperial medical case record in Qing Dynasty.

Clinical efficacy evaluation and potential mechanism of Huanglian Ejiao Decoction in treatment of type 2 diabetes mellitus by Meta-analysis associated network pharmacology / 中草药

Objective: To evaluate the clinical efficacy of Huanglian Ejiao Decoction and explore its mechanism in the treatment of type 2 diabetes (T2DM) based on Meta-analysis and network pharmacology technology. Methods: Firstly, CNKI, VIP, Wanfang, PubMed, the Cochrane Library, and Web of Science were used to find randomized controlled trials of Huanglian Ejiao Decoction for T2DM until May 2020. The included literatures were evaluated according to the Cochrane risk bias assessment tool, and the Review Manager software was used for quantitative synthesis. The chemical components and its targets of Huanglian Ejiao Decoction were screened based on network pharmacology. Common targets were obtained after taking the intersection with T2DM targets. The bioinformatics technology was used to annotate key pathways, and the potential mechanism of Huanglian Ejiao Decoction was explored in the treatment of T2DM. Results: A total of 15 RCTs were selected which included 1 254 patients. Compared with the conventional treatment of western medicine, Huanglian Ejiao Decoction combined with western medicine had a more satisfactory clinical effect, stronger hypoglycemic and hypolipidemic effect. Through network pharmacology methods, 258 chemical components and 985 targets were obtained from online databases. There were 60 components, 121 targets, and 181 pathways closely related to the treatment of T2DM, mainly involving AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, MAPK signaling pathway, insulin resistance, etc. Conclusion According to the existing research, the conventional treatment of western medicine combined with Huanglian Ejiao Decoction can increase the clinical efficacy of T2DM and have better hypoglycemic and hypolipidemic action. T2DM can be cured by improving insulin resistance, reducing inflammation, mitigating oxidative stress and other treatments.

Donkey and Mule Welfare.

Donkeys and mules have been critical to the development of human civilization, since being domesticated some 6000 years ago. However, they suffer from being undervalued or ignored by development agencies and animal protection nongovernmental organizations. Where they are recognized as affecting agriculture and the economy it is often because they are seen as being either invasive pests or an anachronism in the developing countries of the twenty-first century. Even in the wealthier societies of the world, donkeys suffer from ignorance about their proper management or a booming industry in health care products based on donkey skin gelatin and milk byproducts.