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.Effect of Co-treatment Method of Stagnation of Phlegm and Blood Stasis (Danlou Tablet) on Vascular Endothelial Function in Patients with Atherosclerosis
Qian WU ; Xinzheng HOU ; Qianyu LYU ; Xuejiao YE ; Shihan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):168-175
ObjectiveTo clarify the protective effect of Danlou tablet, a representative traditional Chinese medicine of the stagnation of phlegm and blood stasis co-treatment method, on vascular endothelial function in patients with atherosclerosis (AS). MethodsA randomized controlled trial was conducted. From September 2023 to November 2023, a total of 72 patients who were diagnosed at Guang'anmen Hospital, China Academy of Chinese Medical Sciences and met the inclusion and exclusion criteria for carotid atherosclerosis (CAS) combined with coronary atherosclerotic heart disease (CHD) and stable angina pectoris (SAP) were enrolled. The patients were randomly divided into a control group (receiving conventional Western medicine treatment) and an observation group (receiving Danlou tablet combined with conventional Western medicine treatment), with 36 cases in each group. The intervention lasted for 12 weeks. The frequency of angina pectoris attacks was recorded to evaluate the clinical efficacy of Danlou tablet. Peripheral blood samples were collected from patients, and the expression levels of serum endothelial injury markers before and after treatment were detected by enzyme-linked immunosorbent assay (ELISA). The nitrate reductase method was employed to evaluate the protective effect of Danlou tablet on vascular function. The expression levels of serum inflammatory factors and lipoproteins were determined by ELISA and an automatic biochemical analyzer (dynamic timed scatter turbidimetry and enzymatic method) to assess the anti-inflammatory and lipid-regulating effects of Danlou tablet. ResultsIn terms of angina pectoris attacks, compared with that in the control group, the frequency of attacks in the observation group was reduced (P<0.05). In terms of endothelial injury markers, compared with the levels before treatment within the same group, the levels of endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in the peripheral blood of the observation group were decreased (P<0.05), while the levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were increased (P<0.05). Compared with the control group after treatment, the differences in ET-1, NO, ICAM-1, and VCAM-1 were significant (P<0.05). In terms of serum inflammatory factors, after treatment, the interleukin-6 (IL-6) level in the observation group was decreased significantly (P<0.05). Compared with the control group after treatment, the IL-6 level in the observation group was decreased significantly (P<0.01). In terms of serum lipoproteins, after treatment, the level of low-density lipoprotein cholesterol (LDL-C) in the observation group was decreased (P<0.05). After treatment, the level of high-density lipoprotein cholesterol (HDL-C) in the observation group was significantly higher than that in the control group (P<0.05). In terms of safety evaluation, no serious adverse events occurred in either group during the intervention period. ConclusionDanlou tablet applied to patients with CAS combined with CHD can improve endothelial function, reduce inflammatory indicators, alleviate symptoms, improve the quality of life of patients, and demonstrate good safety.
3.Effect of Co-treatment Method of Stagnation of Phlegm and Blood Stasis (Danlou Tablet) on Vascular Endothelial Function in Patients with Atherosclerosis
Qian WU ; Xinzheng HOU ; Qianyu LYU ; Xuejiao YE ; Shihan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):168-175
ObjectiveTo clarify the protective effect of Danlou tablet, a representative traditional Chinese medicine of the stagnation of phlegm and blood stasis co-treatment method, on vascular endothelial function in patients with atherosclerosis (AS). MethodsA randomized controlled trial was conducted. From September 2023 to November 2023, a total of 72 patients who were diagnosed at Guang'anmen Hospital, China Academy of Chinese Medical Sciences and met the inclusion and exclusion criteria for carotid atherosclerosis (CAS) combined with coronary atherosclerotic heart disease (CHD) and stable angina pectoris (SAP) were enrolled. The patients were randomly divided into a control group (receiving conventional Western medicine treatment) and an observation group (receiving Danlou tablet combined with conventional Western medicine treatment), with 36 cases in each group. The intervention lasted for 12 weeks. The frequency of angina pectoris attacks was recorded to evaluate the clinical efficacy of Danlou tablet. Peripheral blood samples were collected from patients, and the expression levels of serum endothelial injury markers before and after treatment were detected by enzyme-linked immunosorbent assay (ELISA). The nitrate reductase method was employed to evaluate the protective effect of Danlou tablet on vascular function. The expression levels of serum inflammatory factors and lipoproteins were determined by ELISA and an automatic biochemical analyzer (dynamic timed scatter turbidimetry and enzymatic method) to assess the anti-inflammatory and lipid-regulating effects of Danlou tablet. ResultsIn terms of angina pectoris attacks, compared with that in the control group, the frequency of attacks in the observation group was reduced (P<0.05). In terms of endothelial injury markers, compared with the levels before treatment within the same group, the levels of endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in the peripheral blood of the observation group were decreased (P<0.05), while the levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were increased (P<0.05). Compared with the control group after treatment, the differences in ET-1, NO, ICAM-1, and VCAM-1 were significant (P<0.05). In terms of serum inflammatory factors, after treatment, the interleukin-6 (IL-6) level in the observation group was decreased significantly (P<0.05). Compared with the control group after treatment, the IL-6 level in the observation group was decreased significantly (P<0.01). In terms of serum lipoproteins, after treatment, the level of low-density lipoprotein cholesterol (LDL-C) in the observation group was decreased (P<0.05). After treatment, the level of high-density lipoprotein cholesterol (HDL-C) in the observation group was significantly higher than that in the control group (P<0.05). In terms of safety evaluation, no serious adverse events occurred in either group during the intervention period. ConclusionDanlou tablet applied to patients with CAS combined with CHD can improve endothelial function, reduce inflammatory indicators, alleviate symptoms, improve the quality of life of patients, and demonstrate good safety.
4.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.
5.Effect of Xiangsha Liu Junzitang Combined with Phlegm-removing and Detoxifying Traditional Chinese Medicine on Immune Escape in Lewis Lung Cancer Mice
Qian YANG ; Shumei WANG ; Shihan FENG ; Xue ZHAN ; Lintao XIA ; Mingxing WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):78-86
ObjectiveTo study the effect and mechanism of Xiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine on immune escape in Lewis lung cancer mice. MethodA total of 60 specific-pathogen-free (SPF)-grade C57BL/6J male mice were injected subcutaneously with 0.2 mL of Lewis cell suspension (containing 2×106 cells·mL-1) in the right mid-axillary line. After 7 days, the mice that had been successfully modeled were randomly divided into six groups: the model group, the cisplatin group, the Xiangsha Liu Junzitang low-, medium-, and high-dose groups, and the combined group, with 10 mice in each group. The Xiangsha Liu Junzitang low-, medium- and high-dose groups were gavaged with 17.88, 35.75, 71.50 g·kg-1 Xiangsha Liu Junzitang solution once a day, respectively, and the dosage of cisplatin intraperitoneally injected into the mice was converted to 5 mg·kg-1 twice a week, and the tumour volumes of each group were measured every two days. The intervention lasted for 14 consecutive days. At the end of treatment, the tumour mass of mice in each group was weighed and the tumour inhibition rate was calculated. The morphological characteristics of tumours in each group were observed by hematoxylin-eosin (HE) staining. Fluorescent quantitative real-time polymerase chain reaction (Real-time PCR) assay was used to detect messenger ribonucleic acid (mRNA) contents of the natural killer group 2 member D (NKG2D) receptor, ribonucleic acid export-1 (RAE-1), and γ interferon (IFN-γ) in the tumour tissues of each group. NKG2D, RAE-1, and IFN-γ mRNA in tumour tissues of each group. Immunohistochemistry (IHC) and Western blot were applied to detect the expressions of RAE-1, NKG2D, and IFN-γ in tumour tissues of each group, and Western blot was used to detect the expressions of interleukin-6 (IL-6), Janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 in tumour tissues of each group, as well as the protein levels of NKG2D, and RAE-1 in spleen tissues of each group. ResultCompared with that in the model group, the tumour mass decreased in all dose groups of Xiangsha Liu Junzitang, with no statistically significant difference. The tumour volume was reduced (P<0.05, P <0.01). The pathological morphology was improved. The mRNA contents of NKG2D, RAE-1 and IFN-γ were increased in the medium-dose group (P<0.05, P<0.01), and the protein expressions of NKG2D, RAE-1, and IFN-γ in tumour tissues were elevated (P<0.05, P<0.01), and p-JAK2 and p-STAT3 protein expressions were decreased (P<0.05, P<0.01). In spleen tissues, the protein expressions of NKG2D and RAE-1 in all dose groups of Xiangsha Liu Junzitang were significantly elevated (P<0.01). Compared with those in the cisplatin group, NKG2D, RAE-1 and IFN-γ mRNA contents were elevated in the middle-dose group of Xiangsha Liu Junzitang, and the difference was not statistically significant. IHC showed that the protein expressions of NKG2D and IFN-γ in the combined group were significantly elevated (P<0.01), and Western blot results showed that the protein expressions of RAE-1, NKG2D and IFN-γ were elevated (P<0.05, P<0.01). p-JAK2 and p-STAT3 protein expressions were decreased in the combined group (P<0.05, P<0.01). NKG2D and RAE-1 protein expressions were significantly increased in spleen tissues of the medium-dose groups and the combined group (P<0.01). ConclusionXiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine can inhibit the growth of tumours in Lewis lung cancer mice by up-regulating the expressions of RAE-1/NKG2D, promoting the activation of NK cells, and inhibiting immune escape, the mechanism of which may be related to down-regulation of the JAK2/STAT3 pathway.
6.Analysis of the current situation of comprehensive management at intensive diabetes treatment clinic in Peking Union Medical College Hospital
Shihan WANG ; Tianyi ZHAO ; Yong FU ; Yingyue DONG ; Tao YUAN ; Weigang ZHAO
Chinese Journal of Clinical Nutrition 2024;32(1):25-34
Objective:To assess the goal fulfillment in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three in patients with diabetes who received intensified treatment at Peking Union Medical College Hospital and regular follow-up for 12 months, analyze the influencing factors, and explore the comprehensive management model for intensive diabetes treatment outpatient services.Methods:This study was a prospective, observational cohort study. The diabetes patients who received long-term regular follow-up at the intensive diabetes treatment outpatient clinic of Peking Union Medical College Hospital from 2012 to 2023 were selected as the research subjects. They were followed up and clinical data were collected at the 1st, 3rd, 6th, 9th, and 12th months of follow-up. The study assessed the goal fulfillment rates in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three, with the goals of glycated hemoglobin (HbA1c)<7%, blood pressure<130/80 mmHg, and low-density lipoprotein cholesterol (LDL-C)<2.6 mmol/L. The study also analyzed the impact of factors, including gender, age, type of diabetes, duration of diabetes, body mass index, comorbidities, complications, and treatment regimens, on the outcomes of comprehensive diabetes management.Results:A total of 232 patients were included in the study, of whom 210 were with type 2 diabetes (90.5%), 13 with type 1 diabetes (5.6%), 5 with latent autoimmune diabetes of the adult (2.2%), 3 with diabetes after total pancreatectomy (1.3%), and 1 with mitochondrial diabetes (0.4%). After 3 months of intensified management, the goal fulfillment rates of blood glucose (67.7% vs. 34.1%, Kappa=0.336, P<0.001), blood pressure (53.4% vs. 37.5%, Kappa=0.159, P=0.001), blood lipid (59.1% vs. 39.2%, Kappa=0.198, P<0.001), and the composite indicator (20.7% vs. 3.0%, Kappa=0.177, P<0.001) were significantly increased. Continued treatment at 6, 9, and 12 months showed stable and sustained increases in the goal fulfillment rates of blood glucose, blood pressure, blood lipid, and the composite indicator. Logistic regression analysis showed that baseline hyperglycemia ( P=0.002), disease duration ≥5 years ( P<0.001), smoking ( P=0.009), alcohol consumption ( P=0.038), presence of diabetic complications ( P=0.001), combination therapy with oral antidiabetic drugs and insulin ( P<0.001), and use of antiplatelet drugs ( P=0.037) were risk factors for uncontrolled HbA1c. Baseline hypertension ( P<0.001), alcohol consumption ( P=0.030), and comorbid dyslipidemia ( P=0.028) were risk factors for uncontrolled blood pressure. Baseline uncontrolled LDL-C ( P=0.020) and non-use of statins ( P<0.001) were risk factors for uncontrolled blood lipid. Conclusions:Among patients with the long-term follow-up at our intensive diabetes treatment clinic, the goal fulfillment rates of blood glucose, blood lipid, blood pressure, and the composite indicator of these three are relatively higher. However, it is still necessary to improve patient compliance as much as possible, emphasize weight management, and persist on the comprehensive diabetes treatment.
7.Macrophage polarization on transition from acute kidney injury to chronic kidney disease
Chinese Journal of Immunology 2024;40(12):2685-2688,后插1-后插2
With development of times and progress of science,recent research supports hypothesis of acute kidney injury switching to chronic kidney disease in context of inflammation,and intensive study of macrophages shows that polarization of macro-phages plays a key role in regulating progression of inflammatory response.But clinical for kidney disease patients with macrophage mediated inflammation there is no clear unified treatment.This paper summaries latest progress of macrophage polarization path,new treatment targets of blocking acute kidney injury to chronic kidney disease,and future research should determine whether biologics,such as clusterin,can provide more opportunities for drug treatment of kidney inflammation and fibrosis.
8.Treatment of Obstructive Sleep Apnea based on Latent Pathogen Theory
Fang ZHANG ; Jiameng ZHANG ; Yihang DU ; Shihan WANG ; Yongjun BIAN
Journal of Traditional Chinese Medicine 2023;64(23):2480-2484
Obstructive sleep apnea (OSA) is a sleep disorder with a slow course and is often accompanied by multiple serious complications, having highly consistent pathogenic characteristics with the latent pathogen. By exploreing its pathogenesis and treatment based on the latent pathogen theory in traditional Chinese medicine, it is believed that congenital healthy qi deficiency is the root, while internal latent phlegm and stasis is the branch, and external pathogenic seven emotions are causing factors. In terms of treatment, it is necessary to target at root deficiency and use nourishing medicinals according to depletion degree of lungs, spleen, and kidneys. When protecting the healthy qi, it is important to prevent the generation and inducing of latent pathogen. Simultaneously, it is also critical to put focus on phlegm stasis by clearing existing latent pathogens with medicinals having the function of dissolving phlegm and dispelling stasis, as well as regulating liver and lung qi. All these are expected to provide new ideas and methods for the treatment of OSA patients in clinical practice.
9.Systemic antibiotics increase microbiota pathogenicity and oral bone loss.
Xulei YUAN ; Fuyuan ZHOU ; He WANG ; Xinxin XU ; Shihan XU ; Chuangwei ZHANG ; Yanan ZHANG ; Miao LU ; Yang ZHANG ; Mengjiao ZHOU ; Han LI ; Ximu ZHANG ; Tingwei ZHANG ; Jinlin SONG
International Journal of Oral Science 2023;15(1):4-4
Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
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Periodontitis/chemically induced*
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Cytokines
10.One case of myeloid sarcoma with multiple space occupying lesions in the spinal canal
Shihan WANG ; Yuhan GAO ; Lu ZHANG
Chinese Journal of Neurology 2023;56(8):915-917
Myeloid sarcoma (MS) is a tumor mass formed by the proliferation of one or more myeloid primitive cells outside the marrow, which is mostly related to acute myeloid leukemia (AML). It is reported that 2.5% to 9.1% of AML patients have MS, and AML with spinal canal MS is very rare. Spinal canal MS often has an acute onset and is difficult to diagnose. It is easy to cause missed diagnosis and misdiagnosis, which will lead to a delay in accurate diagnosis seriously affecting the treatment and quality of life among these patients. The clinical data, diagnosis and treatment process of a case of MS with multiple space occupying lesions in the spinal canal diagnosed and treated by the Department of Hematology of Peking Union Medical College Hospital are reported, in order to provide reference for clinical workers.

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