1.Effect of Different Degrees of Blood Stasis on Cognitive Function and Plasma Differential Metabolites in Patients with Coronary Heart Disease
Shihan XU ; Yanfei LIU ; Fenglan LIU ; Qing WANG ; Fengqin XU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):167-176
ObjectiveTo explore the correlation between the blood stasis score of coronary heart disease(CAD) and mild cognitive impairment(MCI), as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI(CADMCI) through a cross-sectional study, and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients. MethodsAccording to the diagnostic criteria of CAD and CAD blood stasis, patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included. According to the Montreal Cognitive Assessment(MoCA) scale score, the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group. The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model. The receiver operating characteristic(ROC) curve was drawn, and the area under the curve(AUC) was calculated to evaluate the sensitivity and specificity of the model. According to the blood stasis score, the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detect plasma metabolites in each group of patients. The differential metabolites were screened according to variable importance in the projection(VIP) value≥1, fold change(FC)<0.67 or >1.5, and P<0.05. ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples. ResultsA total of 266 CAD patients were included in this study. Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI[odds ratio(OR)=1.619, 95% confidence interval(CI) 1.223-2.142, P<0.001, ROC curve AUC was 0.615(95% CI 0.547-0.683, P=0.001)], indicating that the CAD blood stasis score has a certain predictive value for MCI. Plasma non-targeted metabolomics analysis showed that the main differential metabolites between CAD blood stasis and CADMCI blood stasis were lipid metabolites, among which phosphatidylcholine[20∶4(5Z, 8Z, 11Z, 14Z)/P-18∶1(11Z)] had the best discriminatory efficiency(ROC curve AUC=0.867, 95% CI 0.754-0.942). Further analysis of the differential metabolites between mild and severe blood stasis showed that lipid metabolites were also the main differential metabolites between mild and severe blood stasis. Among them, 1α,25-dihydroxy-2β-(2-hydroxyethoxy) vitamin D3 had the best efficacy in distinguishing mild and severe CAD blood stasis(AUC=0.813, 95% CI 0.649-0.951), and phosphatidylcholine 34∶2 had the best efficacy in distinguishing mild and severe CADMCI blood stasis(AUC=0.819, 95% CI 0.640-0.941). ConclusionThere is a significant correlation between CAD blood stasis score and MCI. Phosphatidylcholine metabolites play an important role in the pathogenesis of CADMCI blood stasis and severe blood stasis. The CAD blood stasis score combined with the detection of phosphatidylcholine metabolites can provide a reference for the development of early and efficient identification strategies for CADMCI.
2.Exploring Role of Energy Dyshomeostasis in Metabolic Dysfunction-associated Fatty Liver Disease Panvasculopathy from Theory of Liver Being Substantial Yin and Functional Yang
Jing CUI ; Qian XU ; Wenting WANG ; Mengmeng ZHU ; Yanfei LIU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):227-233
Liver being substantial Yin and functional Yang maintain normal function of Qi, blood and meridians. In clinical practice, it is often found that pan-vascular lesions with atherosclerosis as the predominant pathological change often co-occur with metabolic dysfunction-associated fatty liver disease(MAFLD). MAFLD leads to increased risk and worse prognosis for many pan-vascular diseases, including cardiovascular disease. Dysregulation of energy homeostasis disrupts the hepatic homeostasis of body use, and representative drugs to improve metabolism, such as metformin, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 agonists, not only have a clear cardiovascular benefit, potential improvement of MAFLD has also been demonstrated. The liver stores blood and the heart pumps blood, and liver diseases affect the heart, that's why the unsmoothness of vessels appears. So the treatment should from the standpoint of liver, restoring liver function, soothing the liver and nourishing heart, activating blood and dredging meridian. It is of great significance to explore in depth the pathogenesis and treatment of pan-vascular lesions caused by MAFLD, and to restore the energy homeostasis by adjusting the balance of liver Yin and Yang.
3.Exploring Role of Energy Dyshomeostasis in Metabolic Dysfunction-associated Fatty Liver Disease Panvasculopathy from Theory of Liver Being Substantial Yin and Functional Yang
Jing CUI ; Qian XU ; Wenting WANG ; Mengmeng ZHU ; Yanfei LIU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):227-233
Liver being substantial Yin and functional Yang maintain normal function of Qi, blood and meridians. In clinical practice, it is often found that pan-vascular lesions with atherosclerosis as the predominant pathological change often co-occur with metabolic dysfunction-associated fatty liver disease(MAFLD). MAFLD leads to increased risk and worse prognosis for many pan-vascular diseases, including cardiovascular disease. Dysregulation of energy homeostasis disrupts the hepatic homeostasis of body use, and representative drugs to improve metabolism, such as metformin, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 agonists, not only have a clear cardiovascular benefit, potential improvement of MAFLD has also been demonstrated. The liver stores blood and the heart pumps blood, and liver diseases affect the heart, that's why the unsmoothness of vessels appears. So the treatment should from the standpoint of liver, restoring liver function, soothing the liver and nourishing heart, activating blood and dredging meridian. It is of great significance to explore in depth the pathogenesis and treatment of pan-vascular lesions caused by MAFLD, and to restore the energy homeostasis by adjusting the balance of liver Yin and Yang.
4.Effects of aging factors on biological characteristics of dental stem cells
Zhiguo XU ; Yanfei WU ; Zhenhui REN ; Xuwei YANG ; Yikun NIU ; Zhilong DONG ; Wei DU ; Wenling YANG ; Xin XU ; Yi ZHU ; Lefeng LIU ; Chao LIU
Chinese Journal of Tissue Engineering Research 2024;28(19):2996-3002
BACKGROUND:The research of dental stem cells in the fields of regenerative medicine and tissue engineering has been deepening,bringing hope for the repair of tooth-related tissues and the treatment of systemic diseases.However,there is a lack of systematic research and analysis on the biological characteristics of dental stem cells in different age groups. OBJECTIVE:To explore the biological characteristics of the human deciduous tooth and permanent tooth pulp stem cells cultured in umbilical cord blood platelet lysate to provide a reliable basis for human platelet lysates to replace fetal bovine serum. METHODS:The pulp tissues of deciduous teeth,juvenile permanent teeth and adult permanent teeth were taken out and cultured in DMEM/F-12 medium supplemented with 10%fetal bovine serum or different concentrations(5%,10%and 15%)of human platelet lysates.Cell proliferation in the four groups was detected by cytometry.The optimal concentration of human platelet lysates was selected for subsequent experiments.Under the optimal concentration of human platelet lysates,human deciduous tooth and juvenile and adult permanent tooth pulp stem cells were cultured in vitro.The cell growth status was observed under the microscope.The specific antigen on the cell surface was detected by flow cytometry.The cell proliferation ability was tested by the cell counting method and CCK-8 assay.The cell differentiation ability in vitro was observed by a three-line differentiation assay. RESULTS AND CONCLUSION:(1)The cell proliferation rate of the 10%human platelet lysate group was the highest.(2)In all three groups,fusiform fibrous cells grew and expanded from around the tissue block.There was no significant difference between deciduous teeth and juvenile permanent tooth cells,but the adult permanent tooth cells were larger than the deciduous and juvenile permanent tooth cells of the same generation.(3)The results of flow cytometry showed that deciduous teeth,juvenile permanent teeth and adult permanent teeth conformed to the phenotypic characteristics of mesenchymal stem cells.(4)The proliferative capacity of adult permanent dental pulp stem cells was significantly lower than those of deciduous teeth and juvenile permanent dental pulp stem cells(P<0.01).(5)mRNA expressions of osteoblast-related genes alkaline phosphatase and bone morphogenetic protein 2,lipoprotein lipase and peroxisome proliferator-activated receptor γ2,mRNA expressions of chondroblast related gene type II collagen α1 and cartilage oligomeric matrix protein in adult pulp stem cells of permanent teeth were significantly lower than those of deciduous teeth and juvenile permanent teeth pulp stem cells(P<0.01).(6)Compared with adult dental pulp stem cells,human deciduous teeth and juvenile permanent teeth dental pulp stem cells have the stronger proliferative capacity and multidirectional differentiation potential,and are more suitable for clinical research and disease treatment.
5.Exploring Modern Mechanism of Treating Diabetic Retinopathy and Coronary Heart Disease from Perspective of Blood Stasis Under Viewpoint of Treating Different Diseases with the Same Method
Ziyu WANG ; Wenting WANG ; Shihan XU ; Yanfei LIU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):197-205
Diabetic retinopathy(DR) and coronary heart disease(CHD) are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice, it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine(TCM). According to TCM, the heart and eyes physiologically communicate with each other by taking Qi, blood and veins as bridges, blood stasis obstructing collaterals is the common TCM etiology of DR and CHD, whose mechanism involves inflammation, oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities, possibly by inhibiting the expression of interleukin-1β(IL-1β), endothelin-1(ET-1) and hypoxia inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF), regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) pathway, initiating adenosine monophosphate(AMP)-activated protein kinase/silent information regulator 1(AMPK/SIRT1) and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathways, inhibiting Hippo/Yes-associated protein(Hippo/YAP) signaling pathway, inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD, which provides a multi-component, multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this, subsequent studies should focus on constructing clinically relevant comorbidity models, conducting multicenter prospective studies, and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases, so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.
6.Effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension
Wenqian ZHAI ; Yanfei BIAN ; Yuezi SONG ; Yunfei LI ; Hong XU ; Zhigang GUO ; Jiange HAN
Chinese Journal of Anesthesiology 2024;44(3):313-317
Objective:To evaluate the effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) by the random number table method: control group (CM group), sevoflurane group (CS group), monocrotaline group (M group) and sevoflurane + monocrotaline group (S group). Monocrotaline 60 mg/kg was intraperitoneally injected in group M and group S, and monocrotaline lysate was intraperitoneally injected in group CM. The rats in S and CS groups inhaled 2.5% sevoflurane for 1 h, twice a week, at an interval of 3 days starting from the first day after injection of monocrotaline. Pulmonary artery acceleration time and pulmonary artery ejection time were measured by transthoracic echocardiography at 6 weeks after monocrotaline injection. The chest was exposed under 3% sevoflurane anesthesia, the heart was perfused, and the pulmonary artery branch and right ventricular myocardial tissues were retained. The wall thickness of pulmonary arterioles and cross-section area of right ventricular cardiomyocytes were observed by HE staining. The expression of Ca 2+ transporter in right ventricular cardiomyocytes was detected by Western blot. Results:Compared with CM group, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly decreased, the cross-section area of right ventricular cardiomyocytes was increased, the wall thickness of pulmonary arteriole was increased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was up-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was down-regulated in M group ( P<0.01). Compared with group M, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly increased, the cross-section area of right ventricular cardiomyocytes was decreased, the wall thickness of pulmonary arteriole was decreased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was down-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was up-regulated in group S ( P<0.01). Conclusions:The mechanism by which sevoflurane improves right ventricular remodeling is related to regulating the expression of Ca 2+ transporter in cardiomyocytes of rats with pulmonary arterial hypertension.
7.Status Analysis of Unplanned Reoperation in Cardiac Surgery Department of a Provincial Grade A Tertiary General Hospital
Mingjuan XIA ; Kun LI ; Ying LIAN ; Rucai ZHAN ; Yanfei SU ; Lingchen KONG ; Min XU
Chinese Hospital Management 2024;44(2):67-71
Objective To analyze the current situation of unplanned reoperation in cardiac surgery and to discuss the management measures of unplanned reoperation.Methods The information of patients undergoing cardiac surgery in a class A tertiary comprehensive hospital during 2018-2022 was collected to analyze the incidence of unplanned reoperation,major ca uses,disease types,surgica l moda lities and Complications.Results A tota l of 3902 patients underwent surgery,of whom 73(1.87%)underwent unplanned reoperation.The main cause of unplanned reoperation was bleeding(50%).The disease types with the highest unplanned reoperation composition ratio were coronary heart disease(38.4%),and the disease types with the highest incidence were dilated cardiomyopathy(11.1%).The average hospitalization cost,the average length of hospitalization,mortality rate and medical dispute rate of patients who had unplanned reoperation were significantly higher than those who did not have unplanned reoperation,the difference was statistically significant(P=0.001).Conclusion The hospital should strengthen the perioperative management of cardiac surgery,focus on supervising disease types and surgical modalities with high incidence of unplanned reoperation,and strictly implement the system of operation classification and the system of reporting unplanned reoperation to ensure the quality of patient surgery.
8.Relationship Between Gut Microbiota Dysbiosis and Cardiometabolic Diseases Based on "Heart-spleen-intestine" Axis
Qian XU ; Wenting WANG ; Yiwen LI ; Jing CUI ; Mengmeng ZHU ; Yanfei LIU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):203-211
Cardiometabolic disease is a clinical syndrome with a causal relationship between metabolic abnormalities and cardiovascular damage. With its global incidence and related mortality rates continually rising, it has become a major health concern worldwide. The role of the gut microbiome and its metabolic products in cardiovascular metabolic health has received widespread attention, with gut microbiota dysbiosis considered a key factor in promoting the development of cardiometabolic disease. Dysbiosis disrupts the balance of the "heart-spleen-intestine" axis, leading to dysfunction of the spleen and intestines, which triggers metabolic disorders and accelerates the progression of cardiometabolic disease. Cardiac dysfunction can also negatively affect spleen and intestinal function, leading to imbalances in the heart and spleen, disharmony in Qi and blood, and exacerbating metabolic anomalies and further dysbiosis, thus forming a vicious cycle. From a modern biological perspective, the gut microbiome and its metabolic products can influence disease progression by modulating inflammatory responses and immune imbalances, leading to endothelial dysfunction and metabolic disorders, thereby increasing the risk of cardiometabolic disease. Additionally, the article proposes strategies for managing cardiometabolic disease by regulating the gut microbiome through a combination of Chinese and western medicine approaches. Traditional Chinese medicine(TCM) treatment starts from the gut microbiome, using the "heart-spleen-intestine" axis as a mediator to regulate cardiovascular metabolic health, highlighting the unique advantages of TCM in targeting the gut microbiome to treat cardiometabolic disease. This article takes the TCM theory of the "heart-spleen-intestine" axis as a starting point, discusses the pivotal role played by this axis in the connection between gut microbiome dysbiosis and the development of cardiometabolic disease, aiming to provide a new perspective for the integrated traditional Chinese and western medical research on cardiometabolic disease, offering scientific evidence and practical guidance to improve the prognosis and quality of life for patients.
9.Clinical features of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma: a multi-center real-world retrospective study
Yunze XU ; Wen KONG ; Ming CAO ; Guangxi SUN ; Jinge ZHAO ; Songyang LIU ; Zhiling ZHANG ; Liru HE ; Xiaoqun YANG ; Haizhou ZHANG ; Lieyu XU ; Yanfei YU ; Hang WANG ; Honggang QI ; Tianyuan XU ; Bo YANG ; Yichu YUAN ; Dongning CHEN ; Dengqiang LIN ; Fangjian ZHOU ; Qiang WEI ; Wei XUE ; Xin MA ; Pei DONG ; Hao ZENG ; Jin ZHANG
Chinese Journal of Urology 2024;45(3):161-167
Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.
10.Status of hepatitis E virus infection in unpaid blood donors in Wenzhou of Zhejiang Province
Shufeng CAI ; Zimiao ZHU ; Yanfei LIU ; Weirui XU ; Shiyao ZHU ; Lulu YE
Chinese Journal of Primary Medicine and Pharmacy 2024;31(6):863-868
Objective:To investigate the status of hepatitis E virus infection in unpaid blood donors in Wenzhou.Methods:A total of 5 241 blood samples were selected from donors who successfully donated blood between October 2022 and March 2023. These samples were tested for hepatitis E virus (HEV) through HEV-IgG antibodies, HEV-IgM antibodies, and nucleic acid tests (HEV RNA). Samples that tested positive for HEV RNA underwent quantitative detection and sequencing. Data regarding the blood donors were collected, the positive rates of each test result were recorded, and the HEV infection status among different populations was analyzed.Results:The positive rate of the HEV-IgG antibody test was 23.60% (1 237/5 241), while the positive rate of the HEV-IgM antibody test was 0.29% (15/5 241). The positive rate of the HEV RNA test was 0.08% (4/5 241). The positive rate of the HEV-IgG test increased with age ( χ2 = 379.493, P < 0.05), and males had a higher positive rate than females ( χ2 = 5.12, P < 0.05). Both the positive rates of HEV-IgG and HEV-IgM tests increased as the number of blood donations increased ( χ2 = 40.87, 8.30, both P < 0.05). Furthermore, the positive rates were significantly higher in 2023 than in 2022 ( χ2 = 51.03, 13.35, both P < 0.05), and they were also significantly higher in spring than in winter ( χ2 = 51.03, 13.35, both P < 0.05). Only one HEV RNA-positive blood donor tested positive for both HEV-IgG and HEV-IgM antibodies, while the remaining three donors tested negative. Only one case was genotyped, and it belonged to genotype Ⅳ. Conclusion:The incidence of HEV infection among unpaid blood donors in Wenzhou of Zhejiang Province is relatively high, with the prevalent HEV genotype being type Ⅳ. Characteristics such as sex, age, and the number of blood donations can be utilized as auxiliary screening reference indicators.

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