1.Analysis of Kidney Differential Metabolites and Hypoxia Adaptation Mechanism of Plateau Pikas Based on UHPLC-QE-MS
Yuxin HE ; Zhenzhong BAI ; Hua XUE ; Zixu GUO ; Xuefeng CAO
Laboratory Animal and Comparative Medicine 2025;45(1):3-12
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.
2.Updates and amendments of the Chinese Pharmacopoeia 2025 Edition (Volume Ⅰ)
LI Hao ; SHEN Mingrui ; ZHANG Pang ; ZHAI Weimin ; NI Long ; HAO Bo ; ZHAO Yuxin ; HE Yi ; MA Shuangcheng ; SHU Rong
Drug Standards of China 2025;26(1):017-022
The Chinese Pharmacopoeia is the legal technical standard which should be followed during the research, production, use, and administration of drugs. At present, the new edition of the Chinese Pharmacopoeia is planned to be promulgated and implemented. This article summarizes and analyzes the main characteristics and the content of updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ), to provide a reference for the correct understanding and accurate implementation the new edition of the pharmacopoeia.
3.Establishment and stress analysis of a finite element model for adolescent cervical disc herniation
Yuxin ZHAO ; Liang LIANG ; Feng JIN ; Yangyang XU ; Zhijie KANG ; Yuan FANG ; Yujie HE ; Xing WANG ; Haiyan WANG ; Xiaohe LI
Chinese Journal of Tissue Engineering Research 2025;29(3):448-454
BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.
4.Current status of anticoccidial drug resistance in China
Yidan BAI ; Wenting LI ; Wanxin LUO ; Yuxin YU ; Dongfang LI ; Junlong ZHAO ; Lan HE
Chinese Journal of Schistosomiasis Control 2025;37(2):217-222
Avian coccidiosis, an acute parasitic disease that mainly harms chicks, is widely prevalent across the world, which poses a serious threat to poultry industry. Because of the single prophylactic formulations, veterinary clinical treatment of coccidiosis mainly relies on chemically synthesized agents, polyether ionophores and Chinese herbal medicines. The introduction of novel anticoccidial drugs is slow for a long period of time, and there is an increasing problem of anticoccidial drug resistance following long-term use, which has become an urgent problem to be solved in poultry industry. This review summarizes the levels of anticoccidial drug resistance across China from 2018 to 2023, and analyzes the resistance to various anticoccidial agents in coccidia. It is indicated that the overall prevalence of anticoccidial drug resistance is high in coccidia, and development of novel anticoccidial agents and products with reduced antibiotics use and alternatives of antibiotics is of an urgent need.
5.Differential Analysis on Chemical Composition and Pharmacodynamic Effect Between Combined Decoction and Single Decoction of Famous Classical Formula Huaganjian
Yang WANG ; Gaoju ZHANG ; Ling LI ; Liping CHEN ; Li ZHANG ; Xiao LIU ; Yuyu ZHANG ; Yuan CUI ; Minglong LI ; Chaomei FU ; Xin YAN ; Yuxin HE ; Qin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):199-207
ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy, to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian, and meanwhile, the contents of four index components(geniposide, paeoniflorin, hesperidin and paeonol) were quantitatively analyzed by high performance liquid chromatography(HPLC). Nonalcoholic fatty liver disease(NAFLD) rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group, model group, lovastatin group(1.8 mg·kg-1), combined decoction group(1.26 g·kg-1) and single decoction group(1.18 g·kg-1). After successful modeling, lovastatin group, combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day, and the control group and model group were given equal amounts of normal saline by intragastric administration, after 4 weeks of administration, the serum and liver tissues were collected, and the contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in serum of rats were detected, and the liver pathological examination was carried out by hematoxylin-eosin(HE) staining and oil red O staining, so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian, and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide, paeoniflorin, hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples(P<0.01). The pharmacodynamic results showed that compared with the model group, both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats, reduce the serum levels of AST, ALT, TC, TG and LDL-C, increase the serum level of HDL-C, and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However, there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition, but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.
6.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
7.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
8.Research on the application rules of aromatic Chinese herbs in the prevention and treatment of warm diseases
Chun WANG ; Linyuan WANG ; Jianjun ZHANG ; Linlin XIU ; Yuyu HE ; Yuxin JIA ; Weican LIANG ; Yi LI ; Yinming ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):451-458
Traditional Chinese medicine (TCM) has historically played a pivotal role in the prevention and treatment of warm diseases, establishing a comprehensive theoretical framework that underpins its practices. The distinctive and indispensable contributions of aromatic Chinese herbs in dispelling harmful influences and mitigating the spread of these diseases are well recognized; however, further investigation is warranted to elucidate their systematic properties and regularities, and the theory of aromatic Chinese herbs in preventing and treating warm diseases still needs to be comprehensively summarized. This study employs the principles rooted in TCM, with particular emphasis on the framework for warm diseases. An analysis of the disease mechanisms, transmission dynamics, and preventive strategies is conducted during the early stage of infection, throughout the course of the disease, and in the post-illness phase. Furthermore, the characteristics and applications of aromatic Chinese herbs are integrated with insights drawn from modern pharmacological research to explore their specific roles in the prevention and management of warm diseases. The utilization of aromatic Chinese herbs manifests in a variety of therapeutic effects: aromatic medicinals purging filth and dispelling pathogens for preventing epidemic disease, aromatic medicinals regulation for relieving superficies syndrome and dispersing evils, aromatic medicinals ventilation the lung to relieve cough and asthma, aromatic medicinals resolving the dampness to awaken the spleen and stomach, aromatic medicinals opening the orifices to restore consciousness, aromatic and pungent medicinals to regulate qi, aromatic medicinals dredging the vessels to activate blood circulation and dissipate blood stasis, and aromatic medicinals clearing latent heat from the yin level. These properties facilitate tailored approaches to address the diverse manifestations of warm diseases and their associated symptoms, providing clear guidance for clinical application to achieve pre-disease prevention, active disease treatment, complication prevention, and post-recovery relapse avoidance. The use of aromatic Chinese herbs in preventing and treating warm diseases demonstrates theoretical, practical, systematic, and regular characteristics. The theory of the properties of aromatic Chinese herbs has been expanded and sublimated in clinical practice, and its scientific connotation has been expounded in modern research. Under the guidance of the theory of treatment based on syndrome differentiation, and by taking into account the distinct stages and pathologies of warm diseases, the rational selection of aromatic Chinese herbs can improve the clinical efficacy.
9.Aging and perioperative brain health: Mechanisms, management, and future.
Peilin CONG ; Qian CHEN ; Qianqian WU ; Jing WANG ; Xinwei HUANG ; Qian ZHANG ; Zheping CHEN ; Huanghui WU ; Yuxin ZHANG ; Mengfan HE ; Zhouxiang LI ; Li TIAN ; Lize XIONG
Chinese Medical Journal 2025;138(19):2381-2398
Globally, over 300 million surgeries are performed each year, and more than 50% of surgeries involve patients aged 65 and older. Aging poses significant challenges to perioperative brain health, as the deterioration of brain structure and function increases susceptibility to postoperative neurological complications. Protecting perioperative brain health remains a worldwide clinical challenge. With senescence, the brain undergoes a progressive decline in homeostasis across various molecular, cellular, and regional functions. Anesthetics and surgical stimuli may accelerate the disruption of brain homeostasis and exacerbate age-related neurodegeneration. This review provides a framework for understanding how anesthesia and surgery can affect brain health in the aging population and contribute to postoperative neurological complications, with a particular focus on perioperative neurocognitive disorder.
10.GPC3-mediated lysosome-targeting chimeras (GLTACs) for targeted degradation of membrane proteins.
Yuxin FANG ; Yaojin ZHU ; Wei WANG ; Zhewei XIA ; Shipeng HE ; Guoqiang DONG ; Chunquan SHENG
Acta Pharmaceutica Sinica B 2025;15(4):2156-2169
Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC WP0 potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.


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