1.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
2.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
3.A retrospective study of the effects of different surgical procedures on the mandibular nerve canal involved by odontogenic keratocyst.
Zeyu WANG ; Chongli DU ; Dong WANG ; Xiao PENG ; Yue DU ; Hanying WANG ; Tingyi GAO ; Rui HAN ; Kai ZHANG
West China Journal of Stomatology 2025;43(1):106-113
OBJECTIVES:
This study aims to evaluate the changes in the mandibular canal following the treatment of large odontogenic keratocysts through decompression and curettage, providing a theoretical basis for sequential treatment.
METHODS:
Twenty patients were selected for each decompression and curettage treatment of large odontogenic keratocysts in the mandible. Postoperative follow-up with was conducted every three months, during which cone beam computed tomography (CBCT) scans were performed. Then, the data were imported into MIMICS software to observe 3D changes in the position and structure of the mandibular nerve canal, followed by a comparative analysis.
RESULTS:
The total displacement of the mandibular canal was (1.89±0.21) mm on the decompression side and (0.80±0.19) mm on the curettage side. Vertically, the displacement range of the mandibular canal on the decompression side (M=1.03, SD=0.17) was larger than on the curettage side (M=0.52, SD=0.010) within nine months post-operation. In the buccal-lingual direction, the ratio of the thickness of the buccal plate to the lingual plate gradually increased with time. The amount of bone reconstruction at the part of the mandibular nerve canal closest to the cyst was (1.75±0.15) mm on the decompression side and (1.45±0.09) mm on the curettage side after nine months.
CONCLUSIONS
The mandibular nerve canal showed varying degrees of recovery and "relocation" after two surgical procedures. Osteogenesis around the mandibular nerve canal was more remarkable after decompression than after curettage. Therefore, for large odontogenic keratocyst, decompression is recommended as the initial treatment, followed by secondary curettage nine months later.
Humans
;
Odontogenic Cysts/diagnostic imaging*
;
Retrospective Studies
;
Cone-Beam Computed Tomography
;
Decompression, Surgical/methods*
;
Mandibular Nerve/surgery*
;
Mandible/innervation*
;
Curettage
;
Male
;
Female
;
Adult
;
Middle Aged
4.Natural course of renal angiomyolipoma and risk factors for its progression
Zhongqing MIAO ; Dong DU ; Zeyu LIN ; Qizhi DU ; Han XUE ; Chunmei LUO ; Kefeng XIAO ; Hongtao JIANG
Chinese Journal of Urology 2025;46(3):192-197
Objective:To clarify the natural course of renal angiomyolipoma and the risk factors for its progression.Methods:This was a retrospective case-control study that included 401 patients diagnosed several times by ultrasound examination in the hospital physical examination system from January 2012 to June 2024. All patients were untreated. There were 128 male cases (31.90%) and 273 female cases (68.10%). The average age at initial diagnosis was (44.04 ± 10.24) years (range 22-78 years). The median longest diameter of the tumor at initial diagnosis was 9.0 (7.0, 11.5) mm. There were 359 cases (89.50%) with single tumors and 42 cases (10.50%) with multiple tumors. The patients were divided into the progression group(≥1 mm/year) and the non-progression group (<1 mm/year)based on the average growth rate of tumor. The differences in gender, age at initial diagnosis, initial tumor size, number of lesions and lesion site between the two groups were compared. Univariate logistic regression analysis was used to explore the relationship between the above factors and the progression of renal angiomyolipoma. Multivariate logistic regression analysis was conducted to identify the risk factors for progression.Results:A total of 401 cases were followed up for an average of (88.15 ± 21.09) months (range 48-140 months). The median maximum diameter of the tumors at the initial diagnosis was 9.0 (7.0, 11.5) mm, and at the end of the follow-up, it was 11 (8, 14) mm. The average growth rate was 0.38 mm/year, and the median growth rate was 0.25 (0, 0.60) mm/year. Among them, 341 cases (85.04%) were in the non-progression group with an average growth rate of 0.14 mm/year, and 60 cases (14.96%) were in the progression group with an average growth rate of 1.74 mm/year. The age of the progression group was lower than that of the non-progression group [(41.43 ± 9.64) years vs. (44.50±10.29) years], the initial maximum diameter of the tumors in the progression group was larger than that in the non-progression group [11.0 (8.0, 16.0) mm vs. 9.0 (7.0, 11.0) mm], and the proportion of multiple tumors in the progression group was higher than that in the non-progression group [14 cases (23.30%) vs. 28 cases (8.20%)], and the differences were all statistically significant ( P<0.05). Age at initial diagnosis( OR=0.96, 95% CI 0.93-0.99), initial tumor size ( OR=1.08, 95% CI 1.04-1.12) and number of lesions ( OR=2.96, 95% CI 1.38-6.34) were the risk factors for the growth of renal angiomyolipoma ( P<0.05), according to the results of multivariate logistic regression analysis. Conclusions:The natural history of most renal angiomyolipoma shows slow growth or relative quiescence, with a small number showing a significant increasing trend. Age at initial diagnosis, initial tumor size and number of lesions were independent risk factors for the growth of renal angiomyolipoma.
5.Mechanism of Yangmai Tongluo formula in treating homocysteine-induced microcirculation disorders based on the acidic sphingomyelinase/endoplasmic reticulum stress pathway
Shengtao XIONG ; Weiyan LIAO ; Qian ZHAO ; Yue XUAN ; Zeyu CHEN ; Donglin LI ; Xiao WANG ; Yang CHEN
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1153-1164
Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P<0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P<0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P<0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P<0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.
6.Mechanism of Yangmai Tongluo formula in treating homocysteine-induced microcirculation disorders based on the acidic sphingomyelinase/endoplasmic reticulum stress pathway
Shengtao XIONG ; Weiyan LIAO ; Qian ZHAO ; Yue XUAN ; Zeyu CHEN ; Donglin LI ; Xiao WANG ; Yang CHEN
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1153-1164
Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P<0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P<0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P<0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P<0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.
7.Natural course of renal angiomyolipoma and risk factors for its progression
Zhongqing MIAO ; Dong DU ; Zeyu LIN ; Qizhi DU ; Han XUE ; Chunmei LUO ; Kefeng XIAO ; Hongtao JIANG
Chinese Journal of Urology 2025;46(3):192-197
Objective:To clarify the natural course of renal angiomyolipoma and the risk factors for its progression.Methods:This was a retrospective case-control study that included 401 patients diagnosed several times by ultrasound examination in the hospital physical examination system from January 2012 to June 2024. All patients were untreated. There were 128 male cases (31.90%) and 273 female cases (68.10%). The average age at initial diagnosis was (44.04 ± 10.24) years (range 22-78 years). The median longest diameter of the tumor at initial diagnosis was 9.0 (7.0, 11.5) mm. There were 359 cases (89.50%) with single tumors and 42 cases (10.50%) with multiple tumors. The patients were divided into the progression group(≥1 mm/year) and the non-progression group (<1 mm/year)based on the average growth rate of tumor. The differences in gender, age at initial diagnosis, initial tumor size, number of lesions and lesion site between the two groups were compared. Univariate logistic regression analysis was used to explore the relationship between the above factors and the progression of renal angiomyolipoma. Multivariate logistic regression analysis was conducted to identify the risk factors for progression.Results:A total of 401 cases were followed up for an average of (88.15 ± 21.09) months (range 48-140 months). The median maximum diameter of the tumors at the initial diagnosis was 9.0 (7.0, 11.5) mm, and at the end of the follow-up, it was 11 (8, 14) mm. The average growth rate was 0.38 mm/year, and the median growth rate was 0.25 (0, 0.60) mm/year. Among them, 341 cases (85.04%) were in the non-progression group with an average growth rate of 0.14 mm/year, and 60 cases (14.96%) were in the progression group with an average growth rate of 1.74 mm/year. The age of the progression group was lower than that of the non-progression group [(41.43 ± 9.64) years vs. (44.50±10.29) years], the initial maximum diameter of the tumors in the progression group was larger than that in the non-progression group [11.0 (8.0, 16.0) mm vs. 9.0 (7.0, 11.0) mm], and the proportion of multiple tumors in the progression group was higher than that in the non-progression group [14 cases (23.30%) vs. 28 cases (8.20%)], and the differences were all statistically significant ( P<0.05). Age at initial diagnosis( OR=0.96, 95% CI 0.93-0.99), initial tumor size ( OR=1.08, 95% CI 1.04-1.12) and number of lesions ( OR=2.96, 95% CI 1.38-6.34) were the risk factors for the growth of renal angiomyolipoma ( P<0.05), according to the results of multivariate logistic regression analysis. Conclusions:The natural history of most renal angiomyolipoma shows slow growth or relative quiescence, with a small number showing a significant increasing trend. Age at initial diagnosis, initial tumor size and number of lesions were independent risk factors for the growth of renal angiomyolipoma.
8.Application of resistance training based on TPB in patients after hip replacement
Ling CHENG ; Yerong LIU ; Jinyu WU ; Zeyu YANG ; Huiyu XU ; Xiaping XIAO
China Modern Doctor 2024;62(29):6-9,14
Objective To investigate the effect of resistance training on the rehabilitation of patients after hip replacement with the framework of the theory of planned behavior(TPB).Methods A total of 85 patients of hip fracture patients in Gansu Provincial Hospital of Traditional Chinese Medicine from July 2022 to April 2023 were selected as research objects.The patients were separated into intervention group(n=43)and control group(n=42)by random sampling.Both groups were treated with routine nursing,and the intervention group was given resistance training based on TPB.The intervention time was 3 months.The Harris hip score(HHS),36-item short form(SF-36)score and Barthel index(BI)scores of the two groups were compared before intervention,1 month and 3 months after intervention,as well as the functional exercise compliance score of the patients 3 months after intervention.Results After 1 month and 3 months of intervention,the HHS,SF-36 score and BI score of intervention group were better than those of control group,and after 3 months of intervention,the executive ability of functional exercise in intervention group was significantly higher than that of control group,and the mean difference was significant(P<0.05).Conclusion Resistance training led by TPB can effectively improve the functional exercise compliance of patients after total hip arthroplasty,improve the muscle strength,balance ability and joint stability of patients,and then improve the daily activity ability and quality of life.
9.Puerarin Alleviates Doxorubicin-induced Cardiomyocyte Toxicity by Activation of Autophagy Through AMPK/ASMase Pathway
Yinping LI ; Yue XUAN ; Weiyan LIAO ; Qian ZHAO ; Qian HE ; Shengtao XIONG ; Zeyu CHEN ; Xiao WANG ; Yang CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1520-1530
Objective To explore the mechanism by which puerarin alleviates the cardiotoxicity induced by doxorubicin in myocardial cells. Methods Cells in the logarithmic growth phase were divided into normal control group,model group,low-(20 mmol·L-1),medium-(40 mmol·L-1) and high-(80 mmol·L-1) dose puerarin groups,and positive control group(captopril,1 mmol·L-1). Except for the normal control group,the other groups were co-incubated with 5 mmol·L-1 doxorubicin. Cell viability was assessed using CCK-8 and lactate dehydrogenase (LDH) assays. ROS levels were detected using a ROS probe. Autophagy flux was detected by transfection with HBAD-mcherry-EGFP-LC3 adenovirus. Western Blot was used to measure the protein expression levels of Beclin-1,LC3,p62,p-AMPKα,and AMPKα. Lysosomal function was assessed using a lysosomal probe. Immunofluorescence was used to detect the relative intensity and co-localization of ASMase and LAMP1. Molecular docking analysis was performed to predict the binding capacity of PUE with ASMase. Differential gene expression was analyzed by gene set enrichment analysis. Results Compared to the normal control group,the model group showed reduced cell viability (P<0.01),increased release levels of LDH and ROS (P<0.05,P<0.01),increased number of autophagosomes (P<0.01),and decreased number of autophagic lysosomes (P<0.05). Beclin-1 protein expression and LC3-II/LC3-I ratio decreased(P<0.01),but p62 protein expression increased(P<0.01). Fluorescence intensity of lysosome decreased(P<0.01),whereas fluorescence intensity of ASMase increased(P<0.01). Immunofluorescence co-localization of ASMase and LAMP1 increased (P<0.01),the ratio of p-AMPKα/AMPKα decreased(P<0.05). Compared to the model group,the high-dose puerarin group showed a rebound in cell viability (P<0.05). The medium-and high-dose puerarin groups showed a decreasing trend in LDH level (P<0.05),and all puerarin groups showed a decreasing trend in ROS level (P<0.01). The number of autophagosomes in high-dose puerarin group reduced (P<0.01). The number of autophagic lysosomes in all puerarin groups increased (P<0.05,P<0.01). The high-dose puerarin group showed increased expression of Beclin-1 (P<0.05) and LC3-II/LC3-I ratio,and decreased p62 expression (P<0.01). All puerarin groups showed increased lysosomal fluorescence intensity (P<0.05,P<0.01). The medium-and high-dose puerarin groups showed a decrease in ASMase fluorescence intensity(P<0.05),a reduction in the immunofluorescence co-localization of ASMase with LAMP1 (P<0.01),and an increase in the p-AMPKα/AMPKα ratio (P<0.01). Molecular docking analysis discovered puerarin showed a binding energy of-8.6 kcal·mol-1 with ASMase. Gene enrichment analysis indicated that the differentially expressed genes in the doxorubicin cardiotoxicity model were related to apoptosis,autophagy,and lysosomal function. Conclusion Puerarin can alleviate doxorubicin-induced cardiotoxicity in myocardial cells and protect myocardial cells by regulating autophagy through AMPK/ASMase,as well as restoring autophagic flux.
10.The current status and prospect of bariatric surgery in the field of kidney transplantation
Zhengfu CHEN ; Lun WANG ; Zeyu WANG ; Zheng ZHANG ; Lifu HU ; Minghao XIAO ; Tao JIANG
Chinese Journal of Urology 2024;45(10):805-808
With the development of social economy and changes of lifestyle, obesity has become a very prominent social problem. Obesity and its-related metabolic diseases such as hypertension and diabetes can promote the occurrence and development of kidney disease, and eventually lead to end-stage renal disease.. Kidney transplantation is the most effective treatment, but obesity increases the risk of surgical complications and poor outcomes. Hence obesity is considered a contraindication for kidney transplantation, as the benefits for obese patients are limited. Therefore, it becomes particularly important for obese patients to gain sufficient weight loss before kidney transplantation, which is not only related to whether transplant candidates are eligible for transplantation, but also the subsequent graft survival rate. Weight loss surgery can help obese patients achieve a significant amount of weight loss more quickly than traditional weight loss methods. In recent years, more and more scholars have applied bariatric surgery to the field of kidney transplantation. Research results have shown that bariatric surgery can improve the transplantation eligibility of kidney transplantation candidates with obesity, increase the survival rate of grafts and the lifetime of patients. Moreover, bariatric surgery can improve kidney function in patients with end-stage renal disease, thereby eliminating the need for kidney transplantation. At present, there is no any literature on the application of bariatric surgery in the field of kidney transplantation in China. This article reviews the current status and prospect of bariatric surgery in the field of kidney transplantation so as to provide reference for clinical practice.

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