Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

Promoting the innovation of the operational assistant service model of public hospitals is an important task to realize the lean operation management of public hospital.Through literature research,four typical operational assistant service models currently implemented in public hospitals in China are summarized:the specialized opera-tional assistant service model,the part-time operational assistant service model,the'team-based'operational assistant service model,and the hybrid financial assistant service model combining full-time and part-time roles.These four models are compared and analyzed from five dimensions:management system,role positioning,per-sonnel composition,selection and training,and service mechanism.Based on this,it is proposed that a new Spe-cialized Multi-Disciplinary Team operational assistant service model should be explored and developed according to local conditions to meet the new requirements for lean operational management and high-quality development of public hospitals in the new era.

The operation assistant work team of public hospitals is an important bridge and link to realize the integration of industry and finance,and an important practitioner to promote the realization of lean operation management.It examines the service model of the operation assistant team engaged in Similar Multi-disciplinary Treatment,focusing on organizational structure,job responsibilities,and service mechanisms.Build a four-tiered lean operational management system and set up an operation assistant work team that combines production,university and research.Based on specific management matters,establish an operation assistant service mechanism such as problem assessment and classification management mechanism,project standardization management mechanism,reward and punishment assessment mechanism,etc.,to promote the optimization and integration of hospital medical education,research,prevention and management and core elements such as human,talent,material and technology resources.Help public hospitals to continuously improve their lean operation management level.

Promoting the innovation of the operational assistant service model of public hospitals is an important task to realize the lean operation management of public hospital.Through literature research,four typical operational assistant service models currently implemented in public hospitals in China are summarized:the specialized opera-tional assistant service model,the part-time operational assistant service model,the'team-based'operational assistant service model,and the hybrid financial assistant service model combining full-time and part-time roles.These four models are compared and analyzed from five dimensions:management system,role positioning,per-sonnel composition,selection and training,and service mechanism.Based on this,it is proposed that a new Spe-cialized Multi-Disciplinary Team operational assistant service model should be explored and developed according to local conditions to meet the new requirements for lean operational management and high-quality development of public hospitals in the new era.

The operation assistant work team of public hospitals is an important bridge and link to realize the integration of industry and finance,and an important practitioner to promote the realization of lean operation management.It examines the service model of the operation assistant team engaged in Similar Multi-disciplinary Treatment,focusing on organizational structure,job responsibilities,and service mechanisms.Build a four-tiered lean operational management system and set up an operation assistant work team that combines production,university and research.Based on specific management matters,establish an operation assistant service mechanism such as problem assessment and classification management mechanism,project standardization management mechanism,reward and punishment assessment mechanism,etc.,to promote the optimization and integration of hospital medical education,research,prevention and management and core elements such as human,talent,material and technology resources.Help public hospitals to continuously improve their lean operation management level.

Objective To investigate the expression of SLC35A2 and PFDN2 in breast cancer and their relationship with clinical indicators and prognosis.Methods TCGA database and TIMER 2.0 database were used to analyze the differences of SLC35A2 and PFDN2 expression in breast cancer tissues and paracancerous tissues;K-M database was used to create the survival curves of patients in the high and low expression groups of the two.qRT-PCR and immunohistochemistry were used to detect the expression of SLC35A2 and PFDN2 in the cancerous and paracancerous tissues,and the expression differences,the relationship between their expression levels and the clinical observation indexes were statistically analyzed,and the independent prognostic factors of breast cancer were screened out;K-M survival analysis was used to compare the prognostic differences between the groups and create the survival curves.Results The expression levels of SLC35A2 and PFDN2 in breast cancer tissues were significantly higher than those in paracancerous tissues according to the results of biopsy,qRT-PCR and immuno-histochemistry,and the expression levels of SLC35A2 were significantly correlated with lymph node metastasis,while the expression of PFDN2 was significantly correlated with the diameter of the tumor and the metastasis of lymph nodes,and the expression of SLC35A2 and PFDN2 was an independent prognostic factor for breast cancer.patients had the worst prognosis.Conclusion The expression of SLC35A2 and PFDN2 in breast cancer tissues was closely related to clinical indicators and prognosis of breast cancer,and could be used as a potential target for breast cancer treatment.

Europe occupies an important position in the world herbal medicine market. The registration of Traditional Chinese Medicine (TCM) in EU is of great significance to the internationalization of TCM. The European Medicines Agency (EMA) has designed a relatively complete management system and regulatory guidelines for the registration and supervision of herbal medicinal products. The promulgation of the DIRECTIVE 2004/24/EC (2004 / 24 / EC) indicates that TCM could enter the EU market through simplified registration. Based on the registration conditions, registration authority and document guideines of Traditional Herbal Medicinal Products (THMPs) in EU, this paper analyzes the application requirements of simple registration of traditional herbal products in EU, and provides suggestions for the simplified registration of TCM in EU according to the registration requirements of medicinal history, quality requirements and application data format.

This paper analyzes the laws, regulations and concre measures of Traditional Chinese Medicine (TCM) in Canada, so as to provide reference for TCM products to enter Canada, and for the establishment of TCM regulation system and the improvement of its detailed rules in China. The regulation of TCM in Canadian, on the one hand, supervision is to provide guidance for the protection of consumers' rights and interests, including the guidance of rational drug use and rational purchase for consumers; on the other hand, it is to supervise enterprises, including the safety, effectiveness and quality certification of TCM products, labeling and packaging requirements, as well as the site certification of product manufacturing, packaging, labeling and import. The Ministry of health of Canada takes evidence as the core of evaluation, and ensures the safe and effective use of TCM products in Canada through product and site licensing evaluation. In the supervision of TCM, relevant departments in China should further strengthen the protection of consumers' drug rights and interests, strengthen the construction of TCM registration evidence system, and pay attention to the risk management of drug production quality.

At present, the registration process of Traditional Chinese Medicine (TCM) in Canada is refering to the requirements of Natural Health Products (NHPs). In terms of registration material, both NHPs and TCM include plants, animals and minerals with medicinal components, but the fundamental difference between them is that TCM is guided by the basic theory of TCM. As for the registration classification of TCM in Canada, first of all, judge whether the product to be applied for is NHPs; Secondly, we should clarify the types and ways of registration, mainly including simple application, traditional application and non-traditional application, and provide application forms, label texts, summary reports, evidence, animal tissue forms, finished product specifications and other materials according to different requirements. At present, the successful registration experience of TCM products in Canada mainly mainly includes applying for superior varieties, selecting appropriate application channels, communicating with local health management units and providing sufficient scientific evidence and good clinical application records. The regulations on the registration of NHPs in Canada have not fully considered the particularity of TCM and the registration of TCM products is still facing some difficulties. In the future, we can learn from the registration process and requirements of the Health Canada, promote the interconnection and mutual recognition of the Pharmacopoeia of the People's Republic of China and the NNHPD monographs in Canada, reduce the obstacles to the local application for registration of TCM, and promote the further improvement of the international standards of TCM.

Traditional Chinese Medicine (TCM) products could be registered as natural health products (NHPs) in Canada. Its registration process could be mainly divided into simple-application, traditional-application and non-traditional application. By analyzingi the TCM registration evidence system and its safety, effectiveness and quality required by different registration categories in Canada, we found that "simple-application" procesure needs to submit evidence based on the parameters of a component in the monograph. As for "traditional application", TCM products need to be used at least 50 years with, traditional material or Pharmacopoeia can be used as evidence; As for non-traditional application, TCM products need to provide evidence according to the disease risk level, and most of them need to provide scientific experiment evidence. Therefore, from the experience of TCM registration evidence system in Canada, the registration of TCM products should pay attention to improve the its classification method, refining its evidence requirements and data types, promoting the formulation of monograph of TCM, realizing the scientific evaluation and rapid review of classic famous prescriptions, and promoting the inheritance and innovative development of TCM in China.