1.Reconsideraton of Stroke with Syndrome of Combined Blood Stasis and Toxin from the Perspective of Xiang Thinking
Yunfan ZHANG ; Di ZHAO ; Lina MIAO ; Hongxi LIU ; Jingjing WEI ; Xiao LIANG ; Liuding WANG ; Xueru ZHANG ; Yunmeng CHEN ; Yunling ZHANG
Journal of Traditional Chinese Medicine 2025;66(13):1305-1310
Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy, reasoning, deduction, and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind, fire, phlegm, and blood stasis" in stroke, thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile, the article traced the construction process of xiang thinking, and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives, state, attribute, origin, and law. Furthermore, the relationship between the process of constructing xiang thinking and the origin of etiology, identification methods, pathogenesis evolution, and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored, so as to provide insights into research on the etiology and pathogenesis of stroke, as well as clinical diagnosis and treatment approaches.
2.Construction of a fall risk prediction model for patients with hematologic malignancies based on the LASSO-Logistic regression
Weifang LI ; Xuebin JI ; Lanhua LI ; Yunling HAN ; Lujing XU ; Xiaoya LIU
Chinese Journal of Practical Nursing 2024;40(23):1789-1795
Objective:To construct a fall risk prediction model for patients with hematologic malignancies and to provide a reference for the risk assessment and accurate management of falls.Methods:The prospective study design was adopted to facilitate the selection of 510 patients with hematologic malignant in Qilu Hospital of Shandong University for investigation, and relevant data such as patient demographic characteristics, disease treatment and drugs were collected. The LASSO-Logistic regression was used to screen the risk factors of falls in patients with hematologic malignancies, to construct a nomogram risk prediction model. The receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the predictive performance of the model. Bootstrap resampling were used to validate internal validation of the model.Results:Among 510 patients with hematological malignancies, there were 273 males and 237 females, aged 53.0 (41.0, 63.0) years old. A total of 6 risk factors were included in the fall risk prediction model for patients with hematological malignancies, which were disease type ( OR = 0.185, 95% CI 0.061 - 0.562), body temperature ≥38 ℃ ( OR = 2.239, 95% CI 1.128 - 4.445), pain ( OR = 15.581, 95% CI 6.592 - 36.829), anemia ( OR = 4.097, 95% CI 1.536 - 10.927), days of bone marrow suppression ( OR = 3.341, 95% CI 1.619 - 6.893), and assessment of daily self-care ability ( OR = 3.160, 95% CI 1.051 - 9.506)(all P<0.05). The ROC curve of the fall risk prediction model was 0.884 (95% CI 0.841-0.927). The optimal threshold, sensitivity, and specificity of the risk prediction model were 0.248, 87.4% and 75.6%. The internal validation C statistic was 0.873. The Calibration curve was almost coincides with the ideal curve, and the model Brier score was 0.080. Conclusions:The constructed fall risk prediction model has good predictive performance, which can efficiently and objectively quantify the risk of falls, and provide a reference for the early assessment and effective prevention of falls in patients with hematological malignancies.
3.Comparison on Rat Models of Acute Cerebral Infarction Due to Stasis Combined with Toxin Complicated with Cerebral-cardiac Syndrome
Mingjiang YAO ; Junyuan LI ; Yue LIU ; Ce CAO ; Guo YUAN ; Lei LI ; Jianxun LIU ; Yunling ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):112-119
ObjectiveTo observe and compare the electrocardiogram index, myocardial morphology, and connexin 43 (Cx43) expression of two rat models of acute cerebral infarction (ACI) due to stasis combined with toxin complicated with cerebral-cardiac syndrome (CCS), and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups (n=10): normal , syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast (CA/Y), multi-infarct induced by micro-embolism (ME), middle cerebral artery occlusion (MCAO), CA/Y+ME, and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan (CA) at 10 mg·kg-1 on the first day and subcutaneous injection with dry yeast (Y) suspension (2 mg·kg-1) on the second day of modeling. Twenty-four hours after the modeling of ACI, the electrocardiograms (ECGs) of rats in each group were collected and the number/percentage (%) of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial injury was assessed by hematoxylin-eosin (HE) staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group, CA/Y+MCAO group had the highest rate of abnormal ECG (P<0.01). Compared with the normal, CA/Y, ME, and CA/Y+ME groups, the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave, shortened P-R interval, and extended Q-T interval, which were particularly obvious in the CA/Y+MCAO group (P<0.05, P<0.01) and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups, especially in the CA/Y+MCAO group (P<0.01). ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover, the CA/Y+MCAO method has higher abnormal electrocardiogram rate, severer myocardial pathological injury, and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.
4.Mechanism of brain-spleen inflammation coupling in a rat model of acute ischemic stroke stasis toxin syndrome
Yilei DONG ; Yue LIU ; Junyuan LI ; Jianhua FU ; Yunling ZHANG ; Mingjiang YAO
Chinese Journal of Comparative Medicine 2024;34(2):45-54
Objective To investigate the correlation between brain injury and spleen damage in a rat model of acute ischemic stroke and stasis interaction,and its effect on the MCP-1/CCR2 axis,and to provide an experimental basis for the mechanism of brain-spleen inflammatory coupling in spleen lesions caused by acute ischemic stroke.Methods Forty male SD rats were randomly divided into a sham group,carrageenan/yeast stasis syndrome group(carrageenan/yeast,CA/Y),middle cerebral artery occlusion group(MCAO),and middle cerebral artery stasis syndrome group(MCAO CA/Y)with 10 rats in each group.CA/Y and MCAO CA/Y groups were injected with 10 mg/kg carrageenan and 10 mg/kg intraperitoneally on the first day of modeling.2 mg/kg of dry yeast suspension were injected subcutaneously on the second day.MCAO and MCAO CA/Y groups were established by wire embolism on the second day.At 24 h after cerebral infarction modeling,the neurological deficit score was calculated in each group,the percentage of the cerebral infarction area was determined by TTC staining,the spleen weight was measured,and the correlation between the percentage of the cerebral infarction area and spleen weight was analyzed by the Spearman correlation coefficient.Furthermore,the pathological morphology of brain and spleen tissues was observed by hematoxylin-eosin(HE)staining,and chemotactic protein 1(MCP-1)and interferon-γ(IFN-γ)contents were measured in rat plasma by enzyme-linked immunosorbent assays.Western blot was used to detect chemokine C-C-motif receptor 2(CCR2)protein expression in the ischemic side of brain tissue.Results Compared with the sham group,the neurological deficit score,cerebral infarction area,and MCP-1 and IFN-γ contents in plasma were significantly increased(P<0.01),spleen weight was decreased significantly(P<0.01),and CCR2 protein expression in brain tissue was significantly upregulated(P<0.05)in MCAO and MCAO CA/Y groups.Moreover,the area of cerebral infarction was increased significantly(P<0.01),the spleen weight was decreased significantly(P<0.01),and CCR2 protein expression in brain and spleen tissues was significantly upregulated(P<0.05)Compared with the MCAO group,the area of cerebral infarction in the MCAO CA/Y group was significantly increased(P<0.01)and the spleen weight was decreased significantly(P<0.05).Spearman correlation analysis showed that the spleen weight was negatively correlated to the percentage of the cerebral infarction area(P<0.01,r=-0.9711).Pathological morphology observation revealed that the pathological changes in the MCAO CA/Y group were the most serious,cerebral liquefaction necrosis foci were seen in the brain tissue cortex,arrangement of neuronal cells in the lesions was sparse and disordered with volume atrophy and a small number of vacuoles and nuclear solidification,most neuronal cells were degenerated and necrotic,microglia hyperplasia was obvious,small blood vessels were significantly increased,and interstitial lipid degeneration was severe.The density of periarterial lymph sheath cells in some of the spleen tissue was reduced and the marginal area is widened.Conclusions A correlation between brain and spleen injury was found after acute ischemic stroke with stasis and toxin syndrome,and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of brain-spleen inflammation coupling.
5.Study on Zhang Yunling's Medication Law in Treating Headache Based on Data Mining
Hongxi LIU ; Xiao LIANG ; Jingzi SHI ; Jingjing WEI ; Wei SHEN ; Guojing FU ; Yue LIU ; Liuding WANG ; Yunling ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):59-64
Objective To study the medication law of Professor Zhang Yunling in the treatment of headache based on data mining technology;To provide ideas for the clinical treatment of headache.Methods Professor Zhang Yunling's outpatient TCM prescription data for the treatment of headache from Sep.2017 to Dec.2020 were collected,and the Ancient and Modern Medical Record Cloud Platform 2.3.5 was used to mine the selected TCM prescriptions for herbal medicine frequency statistics,property,taste and meridian tropism statistics,herbal medicine efficacy statistics,correlation analysis,clustering analysis,complex network analysis,etc.Results Through collection and screening,totally 332 prescriptions were included,involving 178 kinds of Chinese materia medica,with a total frequency of 5 380 times.The top 10 kinds of Chinese materia medica were Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Testudinis Carapax et Plastrum,Bambusae Caulis in Taenia,Glycyrrhizae Radix et Rhizoma,Astragali Radix,Amomi Fructus Rotundus,Pinelliae Rhizoma Praeparatum,and Polygalae Radix.They were mainly warm,mild and slightly cold in properties,sweet,pungent and bitter in tastes,and liver,lung,spleen meridian in meridian tropism.In the statistics of herbal medicine efficacy,expelling wind and relieving pain,suppressing liver yang,promoting blood circulation and qi,clearing heart and relieving restlessness,clearing heat and detoxifying,softening liver and relieving pain were used more frequently.The combinations in herbal medicines association included"Atractyodis Macrocephalae Rhizoma-Chuanxiaong Rhizoma","Testudinis Carapax et Plastrum-Paeoniae Radix alba","Glycyrrhizae Radix et Rhizoma-Paeoniae Radix alba","Testudinis Carapax et Plastrum-Chuanxiaong Rhizoma","Bambusae Caulis in Taenia-Chuanxiaong Rhizoma".Herbal medicines clustering clustered 32 kinds of high-frequency herbal medicines used more than 60 times into 6 categories.Complex network analysis screened out the core formula for the treatment of headache:Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Bambusae Caulis in Taenia,Pinelliae Rhizoma Praeparatum,Testudinis Carapax et Plastrum,Astragali Radix,Amomi Fructus Rotundus,and Glycyrrhizae Radix et Rhizoma.Conclusion In the treatment of headache,Professor Zhang Yunling holds that the pathogenesis of headache is deficiency in origin and excess in superficiality,deficiency of qi and blood,loss of nourishment of brain collaterals,stagnation of phlegm and dampness,disturbance of wind pathogen,obstruction of brain collaterals,and the location of the disease is related to the five viscera and involves the stomach.Focuses on tonifying deficiency and reducing excess,treats exterior and interior separately,and gives consideration to both the symptoms and the root causes,which often uses drugs to treat headache,such as dispelling wind and relieving pain,promoting blood circulation and relieving pain,relieving spasm and relieving pains,eliminating phlegm and dampness,invigorating qi and spleen,nourishing blood and yin,eliminating dampness and regulating stomach,relieving depression and restlessness,which can provide some reference for the clinical treatment of headache.
6.Exploring the Disease Mechanism and Treatment of Ischemic Stroke Based on Ascending and Descending of Qi Movement from the Perspective of Xiang Thinking
Liuding WANG ; Xiao LIANG ; Yifan CHEN ; Yue LIU ; Hongxi LIU ; Di ZHAO ; Yunfan ZHANG ; Yunmeng CHEN ; Xueru ZHANG ; Yunling ZHANG
Journal of Traditional Chinese Medicine 2024;65(14):1443-1448
Xiang thinking is the key way of thinking to construct the life model of human body in traditional Chinese medicine (TCM), and the theory of ascending and descending of qi movement is an important manifestation of xiang thinking in the theory of TCM. Based on the theory of qi movement, this paper interpreted the mechanism of ischemic stroke through the perspective of xiang thinking "earth weakness - wood constraint - fire hyperactivity", as "earth weakness in the central and dampness accumulated to phlegm" "wood constraint and stirring wind led to blood stasis" and "fire hyperactivity and fire toxin showed flaming upward" due to disorder of qi movement. Combined with the "xiang of medicinal properties and therapy methods" to discuss the treatment and prescriptions of ischaemic stroke, applying wind medicinals to elevate ji-earth (己土) and yi-wood (乙木), so that phlegm and stasis can be eliminated, and cold medicinals to descend jia-wood (甲木) and wu-earth (戊土) so that fire toxin can be cleared, with a view to restore ascending and descending of qi movement for ischaemic stroke.
7.Establishment and Evaluation of Animal Models of Combined Stasis and Toxin Syndrome
Yue LIU ; Mingjiang YAO ; Xiao LIANG ; Wenqiang CUI ; Wei SHEN ; Jingjing WEI ; Xiansu CHI ; Hongxi LIU ; Jianxun LIU ; Yunling ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):72-78
ObjectiveTo screen and establish animal models of combined stasis and toxin syndrome based on the comparison of three modeling methods, i.e., carrageenan (Ca), Ca combined with dried yeast (Ca+Yeast), and Ca combined with lipopolysaccharide (Ca+LPS). MethodForty SPF male SD rats were randomly divided into normal group, Ca group, Ca+Yeast group, and Ca+LPS group, with 10 rats in each group. The Ca group, Ca+Yeast group, and Ca+LPS group received an intraperitoneal injection of Ca (10 mg·kg-1) on the first day. The Ca+LPS group received an intraperitoneal injection of LPS (50 μg·kg-1) on the second day, and the Ca+Yeast group received a subcutaneous injection of dry yeast suspension (2 mg·kg-1) on the back on the second day. The rectal temperature of each group was dynamically observed after modeling. After 24 hours of modeling, the macroscopic evaluation indexes, including tongue manifestation, pulse, and black tail length in each group were observed. The PeriCam PSI imaging system was used to detect the blood flow perfusion of the rat tail. The automatic hemorheology analyzer was used to measure the whole blood viscosity and plasma viscosity of each group. The PL platelet function analyzer was used to detect the platelet aggregation rate of the rats. The enzyme-linked immunosorbent assay (ELISA) was used to detect the interleukin-6 (IL-6) level in the rat plasma. The myocardial tissue, brain tissue, and lung tissue of each group of rats were observed by hematoxylin-eosin (HE) staining. ResultCompared with the normal group, all three model groups showed varying degrees of black tail (P<0.05, P<0.01), reduced blood flow perfusion at the tail end (P<0.05, P<0.01), decreased R, G, and B values of tongue manifestation (P<0.05, P<0.01), and increased maximum platelet aggregation rate (P<0.05, P<0.01). The pulse amplitudes of the Ca+Yeast group and the Ca+LPS group were lower than that of the normal group (P<0.05, P<0.01). In addition, the average rectal temperature of the Ca+Yeast group increased after 24 hours of modeling (P<0.01), and the low-, medium-, and high-shear whole blood viscosity and plasma viscosity increased (P<0.05, P<0.01) as compared with those in the normal group. Additionally, the expression level of the plasma inflammatory factor IL-6 was significantly up-regulated (P<0.05). Pathological morphology results showed that the Ca+Yeast group had the most severe pathological changes, with small foci of myocardial fiber dissolution, inflammatory cell infiltration, and fibroblast proliferation observed. In the hippocampal area, the neurons were sparse and had undergone red degeneration. In the small focus of the lung interstitium, lymphocytes and neutrophils were infiltrated. ConclusionThe animal model of combined stasis and toxin syndrome was properly established using Ca+Yeast. The systematic evaluation system of the model, which includes traditional Chinese medicine four diagnostic information, western medicine microscopic indicators, and tissue pathological morphology, is worthy of consideration and reference by researchers.
8.Diagnosis and Treatment of Traditional Chinese Medicine for Encephalopathy Based on the Theory of “Identificating the Onset of Diseases”
Di ZHAO ; Zhenmin XU ; Xiao LIANG ; Hongxi LIU ; Yunling ZHANG
Journal of Traditional Chinese Medicine 2023;64(22):2295-2299
Brain diseases in traditional Chinese medicine were complex and difficult to diagnosis and treatment, and new diagnostic and therapeutic ideas are urgently needed. The onset of the disease was the result of the struggle between healthy qi and pathogenic qi. Common types of the onset of diseases included sudden onset, slow onset, latent onset, secondary onset, and recurrent onset, reflecting the strength of the healthy qi and pathogenic qi, the pathogenic qi that reduced diseases, the site of onset, and other informatin. “Identificating the onset of diseases” was simple and easy to operate, and helped to clarify the complex development of encephalopathy. When applying it, we should first identify urgency and importance, focus on the characteristics; grasp the tendency of diseases, and know the overall situation of the disease; compare similarities and differences horizontally; and carefully observe and dynamically understand the disease. “Identificating the onset of diseases” has the characteristics of comprehensiveness and prognosis, and can lay the foundation for pattern identification and treatment and “treating disease before its onset”.
9.Thought of Treatment of Orifices Based on Correspondence Between Drugs and Symptoms in Chinese Herbal Classics in Past Dynasties
Hongxi LIU ; Jingzi SHI ; Jingjing WEI ; Yue LIU ; Wei SHEN ; Yunmeng CHEN ; Liuding WANG ; Xiansu CHI ; Xiao LIANG ; Yunling ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):185-193
ObjectiveTo discuss the thought of treatment of orifices in the Chinese herbal classics in the past dynasties based on the correspondence between drugs and symptoms to guide the clinical treatment based on syndrome differentiation. MethodAll the literature data of Chinese herbal classics were retrieved from the database of the Chinese Medical Dictionary, involving 76 works of Chinese herbal classics and covering representative works from the Han dynasty to the Ming and Qing dynasties. The information on Chines herbal drugs for the treatment of orifices was collected and sorted out. According to Chinese Materia Medica (11th Edition) and Pharmacopoeia of the People's Republic of China (2020 Edition), the nature, flavor, and meridian tropism of the selected Chinese herbal drugs were statistically analyzed. The pathogenesis elements in the treatment of orifices were classified and counted, and the contents of syndrome differentiation and treatment in various Chinese herbal classics were extracted. ResultIn 76 Chinese herbal classics in the past dynasties, 93 Chinese herbal drugs for the treatment of orifices were selected. The nature of drugs was mainly warm, followed by cold and mild. The flavor was mainly pungent, followed by bitter and sweet. In terms of meridian tropism, drugs mainly acted on the lung meridian, followed by stomach, heart, liver, spleen, and kidney meridians. The pathogenesis elements of orifices could be divided into six categories, i.e., wind invasion, turbid obstruction and Qi stagnation, water and dampness stagnation, blood stasis and collaterals blockage, heat and toxin damage, deficiency of vital Qi and cold coagulation. ConclusionOrifices are mainly treated with drugs effective in dispelling wind and pathogenic factors, resolving turbidity and removing stagnation, inducing diuresis and eliminating dampness, promoting blood circulation and dredging collaterals, clearing heat and purging fire, tonifying deficiency and dispelling cold, which are used in combination. Eliminating pathogenic factors and dredging, tonifying deficiency and purging excess are the main characteristics of treatment of orifices based on syndrome differentiation, which is in line with the physiological dysfunction state of orifices in losing the function, evil Qi blockage and healthy Qi deficiency.
10.Herbal Textural Research on Treatment of Headache Based on Syndrome Differentiation
Hongxi LIU ; Mengying LU ; Xiao LIANG ; Xiansu CHI ; Jingjing WEI ; Yue LIU ; Liuding WANG ; Yunling ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):155-162
ObjectiveTo summarize the thinking of treatment of headache based on syndrome differentiation by reviewing the literature of materia medica in the past dynasties, so as to guide the clinical practice. MethodAll the literature of materia medica in the Chinese Medical Dictionary, involving 76 works from Han to Qing Dynasties, were searched, and the information of the herbs for treating headache was extracted. According to Chinese Materia Medica (11th Edition) and Pharmacopoeia of the People's Republic of China (2020 Edition), the nature, taste, and meridian tropism of the selected herbs were statistically analyzed, and the syndrome elements of headache were classified and counted. In addition, the contents of syndrome differentiation and treatment of headache by different herbs were extracted. ResultFrom the 76 monographs of materia medica in the past dynasties, 114 herbs for treating headache were selected. The herbs mainly had cold or warm nature, pungent or bitter taste, and tropism to the lung and live meridians. The syndrome elements of headache treated by the herbs mainly included wind attack, fire disturbance, turbid obstruction, stagnation, cold coagulation, and healthy Qi deficiency. ConclusionHeadache is mainly treated with the herbs with the effects of dispelling pathogenic wind, clearing heat and purging fire, eliminating phlegm and resolving dampness, regulating Qi movement and activating blood, warming Yang and dispelling cold, and tonifying deficiency and reinforcing healthy Qi, and the herbs are often used in combinations. Headache is treated following the principles of dispelling wind and pathogen, regulating Qi and blood, and tonifying deficiency and purging excess, which is in line with the laws of obstruction and nutrient deficiency causing pain.

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