1.Mechanism Investigation of Qi-invigorating and Blood-activating Drug Combination in Yitangkang Compound Against Diabetic Cardiomyopathy Using Multimodal Research Approach
Chenghao YU ; Tingting LI ; Mingbo ZHANG ; Honghe XIAO ; Yufeng YANG ; Yan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):94-106
ObjectiveThrough multimodal research methods including medication rule mining, network pharmacology, molecular docking and dynamics simulation, and in vivo animal experiments, this study aims to speculate and verify the core composition (Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma) and efficacy (Qi-invigorating and blood-activating) of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy (DCM), investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets, and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database, and the "Analysis Method" module of the platform was applied to mine and summarize medication rules, thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, SwissTargetPrediction platform, GeneCards database, MetaScape database, CytoScape software, etc. Then, molecular docking was performed via the CB-Dock2 platform, and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally, in vivo animal experiments were carried out. Twenty-eight Sprague Dawley (SD) rats meeting the research criteria were divided into a normal group, a model group, a drug combination group (3.3 g·kg-1), and a Yitangkang group (20 g·kg-1). A type 2 diabetes mellitus (T2DM) rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ), followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period, the traditional Chinese medicine (TCM) compound and drug combination were administered for prevention and treatment intervention. Meanwhile, changes in blood glucose, body weight, and heart index of each group were monitored. Cardiac function was assessed by echocardiography, and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin (HE) and Masson staining, and the expression of L-type calcium channel (CACNA1C), calmodulin (CALM1), calcium/calmodulin-dependent protein kinase Ⅱδ (CAMK2D), and neuronal nitric oxide synthase (NOS1) proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions, Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen, heart, and lung, and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis, (Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma)-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination, 714 drug combination action targets, 2 702 disease targets, and 286 intersection targets. Protein-protein interaction (PPI) network predicted nine interaction component-targets (nine active ingredients and four calcium signaling pathway target genes). Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re, 1cll-quercetin, 9blh-(6S)-6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[8,7-g]benzofuran-10,11-dione, and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group, the model group showed significant changes in blood glucose, body weight, myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression levels of CACNA1C, CALM1, CAMK2D, and NOS1 proteins (P<0.05, P<0.01). Compared with the model group, the Yitangkang group had a certain improvement effect on the above indexes (P<0.05, P<0.01). Compared with the Yitangkang group, the drug combination group showed no significant difference in improving myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression of CACNA1C, CALM1, CAMK2D, and NOS1 proteins, except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats, and their mechanism of action may be related to the regulation of the calcium signaling pathway.
2.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
3.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
4.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
5.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
6.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
7.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
8.Treating primary hypotension using the tonifying qi and ascending yang method based on the"yang transforming qi and yin shaping up body"theory
Xuhua JIAO ; Yufeng LI ; Min XIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1591-1596
Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.
9.Expert consensus on the construction, evaluation and application of bone organoids (version 2024)
Jian WANG ; Long BAI ; Xiao CHEN ; Yuanyuan LIU ; Guohui LIU ; Zhongmin SHI ; Kaili LIN ; Chuanglong HE ; Jing WANG ; Zhen GENG ; Weiyang SHI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Lili YANG ; Zhiwei WANG ; Haodong LIN ; Yunfei ZHANG ; Fuxin WEI ; Wei CHEN ; Wenguo CUI ; Fei LUO ; Jun FEI ; Hui XIE ; Jian LUO ; Chengtie WU ; Xuanyong LIU ; Yufeng ZHENG ; Changsheng LIU ; Jiacan SU
Chinese Journal of Trauma 2024;40(11):974-986
Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.
10.Effects of frontoparietal transcranial alternating current stimulation on working memory in different pos-tures
Yufeng ZHANG ; Yanwen XIAO ; Lingyan HUANG
Chinese Journal of Rehabilitation Medicine 2024;39(7):965-970
Objective:To investigate the effect of theta-transcranial alternating current stimulation(θ-tACS)over the frontal-parietal cortex on working memory(WM)performance under different postural conditions(sitting and stand-ing)in healthy adults. Method:The study was a randomized,crossover,double-blind design.Sixteen healthy adults received tACS or sham stimulation in random order,with at least 72 hours interval between two sessions.Seven electrodes were placed in the left frontoparietal critical brain region with 6Hz for 21 mins.The sham stimulation used the same stimulation time and frequency as tACS group,but only 1 minute of stimulation(30s at the beginning and 30s at the end of the stimulation).WM performance was assessed before and immediately after stimulation,in-cluding accuracy,reaction time and inverse efficiency scores.Wilcoxon rank sum tests were used to observe between-and within-group differences on WM performance. Result:Fifteen participants completed the experiment and there were no significant differences in side effects be-tween two groups.There was a significant improvement in reaction time and inverse efficiency scores for sit-ting WM as well as reaction time for standing WM after the frontoparietal θ-tACS(P<0.05).There was a trend towards improvement in inverse efficiency scores for standing WM(P=0.057),while there was no signif-icant difference in accuracy,reaction time and inverse efficiency scores of WM during the sitting and standing conditions in the sham stimulation(all P>0.05). Conclusion:Frontoparietal θ-tACS can improve WM performance in both sitting and standing postures.This helps healthy adults cope with real-life multitasking cognitive activities and has important practical application value.

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