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INTRODUCTION: The abuse of veterinary drugs has emerged as a concerning trend, with global fatalities on the rise. Our understanding of this phenomenon remains limited. This study aims to identify the veterinary drugs being misused, the reasons behind their misuse, and how they are obtained. METHODS: Utilising PubMed, Scopus, and Web of Science databases, along with related grey literature, we applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) framework for data collection. Screening and cross-referencing yielded 66 relevant articles, encompassing case reports, surveys, reports, and systemic literature reviews. The analysis identified 28 distinct veterinary drugs being misused in humans, primarily falling into categories, e.g., α-2- and ß-2-adrenergic receptor agonists, GABAergic receptor modulators, opioid receptor agonists, nonsteroidal anti-inflammatory drugs (NSAIDs), and N-methyl-D-aspartate (NMDA) receptor antagonists. These drugs were used for various purposes, including recreational use, weight loss, bodybuilding, pain relief, and self-medication for stress-related symptoms. RESULTS: Routes of administration predominantly included parenteral, oral, and inhalation methods. Veterinary workers/assistants and individuals connected to animals were identified as contributors to the misuse of these medications. Motivations for their utilisation ranged from affordability and accessibility to the ease of obtaining multiple prescriptions from various veterinary sources, often in conjunction with other illicit substances. Dependence and addiction were common outcomes of the misuse of veterinary medicines by humans. CONCLUSION: Overall, this systematic review underscores the increasing popularity of veterinary prescription drug misuse despite being under-reported with limited available data. Healthcare professionals are urged to remain vigilant to potential overdose events involving these medications.

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Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate, and the survival rate of HCC patients remains low. Animal medicines have been used as potential therapeutic tools throughout the long history due to their different structures of biologically active substances with high affinity to the human body. Here, we focus on the effects and the mechanism of action of animal-derived natural products against HCC, which were searched in databases encompassing Web of Science, PubMed, Embase, Science Direct, Springer Link, and EBSCO. A total of 24 natural products from 12 animals were summarized. Our study found that these natural products have potent anti-hepatocellular carcinoma effects. The mechanism of action involving apoptosis induction, autophagy induction, anti-proliferation, anti-migration, and anti-drug resistance via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Ras/extracellular signal regulated kinases (ERK)/mitogen-activated protein kinase (MAPK), Wnt/ß-catenin, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Huachansu injection and sodium cantharidate have been used in clinical applications with good efficacy. We review the potential of animal-derived natural products and their derivatives in the treatment of HCC to date and summarize their application prospect and toxic side effects, hoping to provide a reference for drug development for HCC.

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Due to the highly stable structure of keratin, the extraction and dissolution steps of animal medicines rich in keratin are complex, which seriously restricts the detection efficiency and flux. Therefore, this study simplified the pre-treatment steps of horn samples and optimized the detection methods of characteristic peptides to improve the efficiency of identifying the specificity of horn-derived animal medicines. For detection of the characteristic peptides in horn-derived animal medicines treated with/without iodoace-tamide(IAA), the ion pair conditions of the characteristic peptides were optimized, and the retention time, intensity and other data of the specific peptides were compared between the samples treated with/without IAA. Two pre-treatment methods, direct enzymatic hydrolysis and total protein extraction followed by enzymatic hydrolysis, were used to prepare horn-derived animal medicine samples. The effects of different methods on the detection of specific peptides in the samples of Saiga antelope horn, water buffalo horn, goat horn, and yak horn were compared regarding the retention time of specific peptides and ion intensity. The results indicated that after direct enzymatic hydrolysis, the specific peptides in the samples without IAA treatment can be detected. Compared with the characteristic peptides in the samples treated with IAA, their retention time shifted back and the mass spectrometry response slightly decreased. The specific peptides of the samples without IAA treatment had good specificity and did not affect the specificity identification of horn-derived animal medicines. Overall, the process of direct enzymatic hydrolysis can be used to treat horn samples, omitting the steps of protein extraction and dithiothreitol and IAA treatment, significantly improving the pre-treatment efficiency without affecting the specificity identification of horn-derived animal medicines. This study provides ideas for quality research and standard improvement of horn-derived animal medicines.

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Animal medicine is a large category of Chinese medicinecommonly used in clinical practice and has important scientific and therapeutic value. Animal medicine isscarcer than herbal medicine. In recent years, with the vigorous development of traditional Chinese medicine(TCM),the contradiction between the increasing industrial demand andsupply of scarce and even endangered medicinal animals has become increasingly prominent. The continuous lack of medicinal animal resources affects the clinical demandandalso causes serious damage to the ecological environment. Only relying on artificial breeding is not enough to alleviate the current condition of depletion. In the face of this dilemma, it is a major challenge for the current industrial development to protect animal resources and meet clinical and industrial needs with "available medicines". The application of substitutes for animal medicines isthe key focus to alleviate this problem, and it is also the key scientific issue to be solved urgently in the modernization of TCM. This paper summarizedand reviewedthe history, current situation, strategies, and methods of animal medicinesubstitution and put forward the point of view of "similar chemical characteristics, similar efficacy, and higher safety" to provide references for scientific substitution and resource protection of rare animals.

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In the present study, the oral bioavailability of cadmium (Cd) in earthworms and leeches was investigated through in vitro physiologically based extraction test (PBET) digestion/Caco2 and MDKC cell models. We are the first to create an innovative assessment strategy which has capacity to offer a more precise evaluation of Cd-associated health risks in traditional animal medicines (TAMs), by combinational usage of bioavailable Cd levels, the duration and frequency of the exposure to TAMs obtained by questionnaire data, as well as safety factor of TAMs. Our data showed that the percentage of bioavailability for Caco-2 cells in earthworms and leeches ranged from 3.29 to 14.17% and 4.32 to 12.61%, respectively. The percentage of bioavailability of MDCK cells in earthworms and leeches ranged from 4.83 to 15.74% and 6.53 to 15.04%, respectively. After adjusting by the bioavailability of Cd to target hazard quotient (THQ), excitingly, our findings manifested that the health risks induced by the ingestion of earthworms and leeches were acceptable in the clinic. Our key findings suggest that bioavailability characterization cannot be ruled out and health risks should be assessed on the basis of the bioavailable Cd levels rather than total levels. Our novel strategy provides insight into the bio-accumulation of Cd in organisms as well as a more realistic and accurate assessment of Cd-associated health risks in TAMs, with the main purpose of improving public health by scientifically using TAMs.

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Animal medicines have been called "medicine with affinity to flesh and blood" by doctors of all ages, which always act as an important branch of Chinese medicine. They have various types, extensive sources and long application history, with unique cli-nical effects in anti-coagulation, anti-thrombosis, anti-fatigue, immune regulation, anti-tumor, anti-convulsion and so on. Most animal medicines contain proteins, fatty acids, and trimethylamine oxides, which are prone to decomposition and produce substances such as biological amines, aldehydes, ketones, alcohols, trimethylamine and ammonia with unpleasant odors. The stench produced by the combination of various odors can easily cause side effects such as nausea and vomiting, which would probably affect the drug compliance and clinical efficacy in patients, and block the development of high-quality animal medicines. At present, we have insufficient understanding on sources and formation mechanism of the stench of animal medicines, lacking development of taste-masking technology. Therefore, the universality, formation, vomiting mechanism, evaluation methods, and masking technology of stench of animal medicines were summarized in this paper, so as to deepen the recognition of stench, provide references for the development of animal medicines deodorization technology, enhance patients' compliance with animal medicines, and promote animal drugs to better serve public health in the new era.

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Few studies reported the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). Currently, oral bioaccessibility of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) present in traditional animal medicines was investigated with physiologically based extraction test-extracted in vitro model. We are the first to develop a health risk assessment strategy by combinational analysis of bioaccessible heavy metal levels to calculate target hazard quotient (THQ), target hazard index (THI) and cancer risk (CR), which has capacity to evaluate the heavy metal associated heath risk of traditional animal medicines. To precisely acquire a realistic risk assessment, questionnaire data was adopted to measure the frequency and duration of the exposure to traditional animal medicines, and the safety factor was highlighted as well. Our data revealed that the bioaccessibility of Hg was the lowest among the five heavy metals. After the adjustment with the bioaccessibility of each heavy metal to target hazard index (THI) values, excitingly, the results manifested that the consumption of traditional animal medicines might not exert an unacceptable health risk in a broad community. In addition, the CR values of As and Pb indicated that the risk of developing cancers was quite lower than their acceptable levels in the clinic.

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Animal medicines have been called "medicine with affinity to flesh and blood" by doctors of all ages, which always act as an important branch of Chinese medicine. They have various types, extensive sources and long application history, with unique cli-nical effects in anti-coagulation, anti-thrombosis, anti-fatigue, immune regulation, anti-tumor, anti-convulsion and so on. Most animal medicines contain proteins, fatty acids, and trimethylamine oxides, which are prone to decomposition and produce substances such as biological amines, aldehydes, ketones, alcohols, trimethylamine and ammonia with unpleasant odors. The stench produced by the combination of various odors can easily cause side effects such as nausea and vomiting, which would probably affect the drug compliance and clinical efficacy in patients, and block the development of high-quality animal medicines. At present, we have insufficient understanding on sources and formation mechanism of the stench of animal medicines, lacking development of taste-masking technology. Therefore, the universality, formation, vomiting mechanism, evaluation methods, and masking technology of stench of animal medicines were summarized in this paper, so as to deepen the recognition of stench, provide references for the development of animal medicines deodorization technology, enhance patients' compliance with animal medicines, and promote animal drugs to better serve public health in the new era.

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The human health is seriously affected by central nervous system(CNS) diseases, but the pathogenesis of CNS diseases is still not completely clear. Currently, the drugs used to treat CNS diseases are mainly receptor modulators and neurotransmitter inhibitors, which have serious side effects; and there are short of drugs for treating CNS diseases clinically. Studies suggest that animal medicines mainly include protein, polypeptide and small-molecule compounds, and have such pharmacological effects in calming, resisting convulsions and improving brain tissues. Plenty of studies suggest that animal medicines usually have a strong activity and good curative effect on these diseases, with a promising prospect in research and development of drugs treating CNS diseases. Based on systematic reviews of literatures, this paper summarizes active ingredients and main pharmacological effects of animal medicines in "extinguishing wind to arrest convulsions" for the CNS diseases, epilepsy and cerebral ischemia, and discusses their study value and application prospects. The results showed that the studies of protein and peptides were relatively simple, and some animal medicines were still blank. The authors believed that amino acids and small molecular compounds should be transferred to oligopeptide, advanced protein extraction and separation techniques shall be adopted for identifying the protein polypeptide composition structure and studying the efficacy, and the methods of biological technology were used to develop peptide biological products for the treatment of CNS diseases. This paper could provide ideas and reference for developing animal medicine products for the treatment of CNS diseases.

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The human health is seriously affected by central nervous system(CNS) diseases, but the pathogenesis of CNS diseases is still not completely clear. Currently, the drugs used to treat CNS diseases are mainly receptor modulators and neurotransmitter inhibitors, which have serious side effects; and there are short of drugs for treating CNS diseases clinically. Studies suggest that animal medicines mainly include protein, polypeptide and small-molecule compounds, and have such pharmacological effects in calming, resisting convulsions and improving brain tissues. Plenty of studies suggest that animal medicines usually have a strong activity and good curative effect on these diseases, with a promising prospect in research and development of drugs treating CNS diseases. Based on systematic reviews of literatures, this paper summarizes active ingredients and main pharmacological effects of animal medicines in "extinguishing wind to arrest convulsions" for the CNS diseases, epilepsy and cerebral ischemia, and discusses their study value and application prospects. The results showed that the studies of protein and peptides were relatively simple, and some animal medicines were still blank. The authors believed that amino acids and small molecular compounds should be transferred to oligopeptide, advanced protein extraction and separation techniques shall be adopted for identifying the protein polypeptide composition structure and studying the efficacy, and the methods of biological technology were used to develop peptide biological products for the treatment of CNS diseases. This paper could provide ideas and reference for developing animal medicine products for the treatment of CNS diseases.

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The DNA extraction method of animal medicine material is difficult and un-unified,which limits the application of molecular identification to identify animal medicines.In this study,based on the DNA extraction theory of SDS,we assessed the effects of three elements including different EDTA concentrations (0.025 mol·L-1,0.25 mol· L-1,and 0.5 mol· L-1) and whether containing NaCl and Triton X-100 in the lysis buffer on the quality of DNA extracted from different kinds of animal medicine.The optimized lysis buffer was used to extract DNA from 121 commercial animal medicines for original and species identification.The results showed that the lysis buffer of 1％ SDS,0.03 mol· L-1 Tris-HCl,0.25 mol· L-1 EDTA and 0.2 mol· L-1 NaCl had the optimum effect on DNA extraction.This lysis buffer can obtain DNA from animal medicine which is difficult to extract,such as Cicadae periostracum.The DNA extractions of 121 commercial animal medicines by optimized lysis buffer can satisfy the experimental requirements for molecular identification.All samples of commercial animal medicines can be accurately identified to the level of species.It was concluded that optimized lysis buffer can be used in the DNA extraction of different kinds of animal medicines except shells,secretions and processed products.This method provides technique support for the molecular identification of animal medicines.

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Objective: To determine the aflatoxins residue of animal medicines by immunoaffinity column HPLC method with post column photochemical derivatization and fluorescence detection, and to evaluate the feasibility of this method. The contamination status of aflatoxins in animal medicines was evaluated according to the determination data of aflatoxin contamination in animal medicines. Methods: After extraction by organic solvent and purification by immunoaffinity column, aflatoxins samples were analyzed by HPLC with fluorescence detection after photochemistry derivation. The recovery rates of aflatoxins in animal medicines, especially the species easily contaminated by aflatoxin, were then determined by adding aflatoxin standard mixtures. Finally, aflatoxins in animal medicines were determined and the results were analyzed. Results: Recovery rates of aflatoxin B1, B2, G1, and G2 were from 70% to 120%. Twenty-four batches of six kinds in 64 batches of 16 kinds of animal medicines were contaminated by aflatoxins, and the contamination rate was 37.5%. Thirteen batches of four kinds of animal medicines exceeded the limit of Chinese Pharmacopoeia of (2015 Edition), and the rate was 20.3%. Conclusion: This method can be used to determine aflatoxins in animal medicines. Some species of animal medicines are likely to be contaminated by aflatoxins, so the aflatoxin control in those animal medicines should be put forward to ensure the safety of drug use.