Biomechanical analysis of the bones in a rat model of osteoporosis based on the combination of disease and syndrome / 中国组织工程研究

BACKGROUND:Kidney deficiency is the main pathogenesis of osteoporosis.To study the relationship between the two major syndrome types of kidney deficiency,Kidney-Yang deficiency and Kidney-Yin deficiency,is beneficial for the development of clinical diagnosis and treatments based on the combination of disease and syndrome. OBJECTIVE:To evaluate the biomechanical differences of the rat femurs with Kidney-Yang deficiency and Kidney-Yin deficiency caused by Yougui pills,and to demonstrate the scientific efficacy of medication based on the combination of disease and syndrome in osteoporosis from a biomechanical perspective. METHODS:The bilateral ovaries of 60 female Sprague-Dawley rats were surgically removed to establish an ovariectomized osteoporosis model.At 10 weeks after modeling,all the rats were randomly divided into a Kidney-Yang deficiency group(n=30)and a Kidney-Yin deficiency group(n=30).Rats with Kidney-Yang deficiency were given gluteal intramuscular injection of hydrocortisone,while rats with Kidney-Yin deficiency were orally administered with thyroid tablet suspension,once a day,for 14 consecutive days.After successful modeling,20 rats in each group were given a suspension of Yougui pills by gavage once a day for 12 consecutive weeks and the remaining 10 rats were used as the control group without intervention.After gavage,the microstructural parameters of the bone were measured using Micro-CT scanning.Three-point bending,finite element simulation,femoral head compression,and surface indentation distribution experiments of the femurs were performed on a mechanical testing machine. RESULTS AND CONCLUSION:Micro-CT revealed that the femoral bone density,bone volume fraction,bone surface density,trabecular number,and trabecular separation were improved in the Kidney-Yin deficiency+Yougui pills group compared with the Kidney-Yin deficiency group(P＜0.05);the femoral bone volume fraction,bone surface density,trabecular number,and trabecular thickness were improved in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group(P＜0.05).The three-point bending experiment showed that the femur elastic modulus,maximum bending strength and bending fracture strength were decreased(P＜0.05)and toughness was increased(P＜0.05)in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group.Finite element simulation showed that Yougui pills could significantly improve the bending resistance of the femurs in the Kidney-Yang deficiency group,but had no significant effect on the Kidney-Yin deficiency group.The femoral head compression experiments showed that Yougui pills could enhance the ability of the femoral head to resist deformation in the Kidney-Yang deficiency group,but there was no significant difference in the effect of Yougui pills on the surface properties of the femoral head in the Kidney-Yin deficiency group and the Kidney-Yang deficiency group.To conclude,Yougui pills can significantly enhance the biomechanical properties of the osteoporotic bones with Kidney-Yang deficiency,but have no significant effect on the osteoporotic bone with Kidney-Yin deficiency.

[Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom].

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 µg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

[Research ideas of core formulas-syndromes based on disease-syndrome-treatment combination].

The relationship between disease and syndrome is a research focus in integrated traditional Chinese and western medicine. Depending on the focus, the disease-syndrome combination for treatment is manifested as the different treatment methods for the same disease and the same treatment method for different diseases based on the syndrome, and different treatment methods for the same syndrome and the same treatment method for different syndromes based on the disease. The mainstream model is the combination of di-sease identification in modern medicine with syndrome identification and core pathogenesis in traditional Chinese medicine. However, current research on the combination of disease and syndrome and core pathogenesis tends to focus on the heterogeneity between disease and syndrome and the separation of syndrome and treatment. Therefore, the study proposed the research idea and model of core formulas-syndromes(CFS). According to the theory of formula-syndrome correspondence, the research idea of CFS deepens the research on core pathogenesis, which aims to summarize the core formulas and syndromes for diseases. The research fields include diagnostic criteria for the indications of formulas, distribution patterns of formulas and syndromes for diseases, the evolution of medicinal-syndrome based on formulas-syndromes, formula combination law based on formulas-syndromes, and the dynamic evolution of formulas-syndromes. Through the summary of ancient classics, clinical experience, and medical records, and with the methods of expert consultation, factor analysis, and clustering analysis, research on the diagnostic criteria for the indications of formulas aims to explore the diagnosis information such as the diseases, symptoms, signs, and pathophysiology. The research on the distribution patterns of formulas and syndromes for diseases tends to summarize the specific types of formulas and syndromes for the diseases through literature research and clinical cross-sectional studies based on the establishment of diagnostic criteria for the indications of formulas. The research on the evolution of medicinal-syndrome aims to clarify the medicinal-syndrome law through literature and clinical research. The formula combination law refers to the fact that the core prescriptions for a disease often appear in combination with other prescriptions on a regular basis. The dynamic evolution of formulas-syndromes refers to the continuous transformation and change of formulas and syndromes in the process of disease development with changes in time and space. The CFS is conducive to the unification of disease, syndrome and treatment and to the deepening of the research model of disease and syndrome integration.

Analysis of Animal Models of Cervical Spondylotic Radiculopathy Based on Characteristics of Clinical Symptoms of Chinese and Western Medicine / 中国实验方剂学杂志

With the acceleration of social rhythm， the progress of science and technology， and the increase of the number of phubbers， the incidence of cervical degenerative diseases is also increasing year by year. Cervical spondylotic radiculopathy（CSR）， as one of the diseases induced by cervical degeneration， has seriously affected people's quality of life and physical and mental health. Traditional Chinese medicine（TCM） is effective in the treatment of CSR， but the theoretical and basic experimental evidence is not sufficient， and the current formulation standard of animal model is not unified. Therefore， based on the clinical guidelines of Chinese and Western medicine for CSR and the characteristics of the disease and syndrome， the author systematically summarized and analyzed the existing animal models， and found that the existing models of microvascular clamp nerve root compression method had a poor agreement with the the Chinese and Western medical guidelines， while the modeling methods of spinal canal insertion， autologous bone insertion compression， stainless steel column compression， and fixed frame cervical degeneration reflected a high degree of agreement in the Western medical guidelines. However， the Chinese medical diagnostic criteria were poorly matched. This indicates that the existing animal models of this disease show few TCM syndrome elements， and lack information collection and evaluation in animal behavioral evaluation similar to the four diagnoses of TCM. In conclusion， this paper aims to systematically evaluate the current status of animal model establishment of CSR based on the concept of combination of disease and syndrome， so as to provide a theoretical basis for the model establishment of CSR that is more consistent with clinical characteristics and symptoms of Chinese and Western medicine.

Research ideas of core formulas-syndromes based on disease-syndrome-treatment combination / 中国中药杂志

The relationship between disease and syndrome is a research focus in integrated traditional Chinese and western medicine. Depending on the focus, the disease-syndrome combination for treatment is manifested as the different treatment methods for the same disease and the same treatment method for different diseases based on the syndrome, and different treatment methods for the same syndrome and the same treatment method for different syndromes based on the disease. The mainstream model is the combination of di-sease identification in modern medicine with syndrome identification and core pathogenesis in traditional Chinese medicine. However, current research on the combination of disease and syndrome and core pathogenesis tends to focus on the heterogeneity between disease and syndrome and the separation of syndrome and treatment. Therefore, the study proposed the research idea and model of core formulas-syndromes(CFS). According to the theory of formula-syndrome correspondence, the research idea of CFS deepens the research on core pathogenesis, which aims to summarize the core formulas and syndromes for diseases. The research fields include diagnostic criteria for the indications of formulas, distribution patterns of formulas and syndromes for diseases, the evolution of medicinal-syndrome based on formulas-syndromes, formula combination law based on formulas-syndromes, and the dynamic evolution of formulas-syndromes. Through the summary of ancient classics, clinical experience, and medical records, and with the methods of expert consultation, factor analysis, and clustering analysis, research on the diagnostic criteria for the indications of formulas aims to explore the diagnosis information such as the diseases, symptoms, signs, and pathophysiology. The research on the distribution patterns of formulas and syndromes for diseases tends to summarize the specific types of formulas and syndromes for the diseases through literature research and clinical cross-sectional studies based on the establishment of diagnostic criteria for the indications of formulas. The research on the evolution of medicinal-syndrome aims to clarify the medicinal-syndrome law through literature and clinical research. The formula combination law refers to the fact that the core prescriptions for a disease often appear in combination with other prescriptions on a regular basis. The dynamic evolution of formulas-syndromes refers to the continuous transformation and change of formulas and syndromes in the process of disease development with changes in time and space. The CFS is conducive to the unification of disease, syndrome and treatment and to the deepening of the research model of disease and syndrome integration.

Comparative Study of Quality of Life Assessment Scales for Bronchiectasis and Thinking of Development of Scales Based on the Mode of Combination of Disease and Syndrome / 中医杂志

This paper summarized the current status of the commonly used quality of life assessment scales of bronchiectasis （BE） at home and abroad， and compared the characteristics and differences of each scale from the basic framework， domain， item pool， application status and quality assessment， so as to provide a basis for the development and application of scales based on the mode of combination of disease and syndrome. There are currently 12 assessment tools for evaluating the quality of life in BE with good reliability， validity， and responsiveness， but only quality of life - bronchiectasis （QOL-B） and bronchiectasis health questionnaire （BHQ） are specifically developed for BE patients. The development process of these scales is mostly rooted in western culture and modern medicine， making it difficult to highlight the characteristics and advantages of traditional Chinese medicine （TCM）. The content of the scales lacks the outcome indicators that BE patients are most concerned about， and cannot fully reflect the subjective feelings of patients. The development and assessment of scales lacks clinical research data and methodological support. Under the guidance of TCM syndrome differentiation and treatment， the development of scales based on the mode of combination of disease and syndrome can emerge the characteristics of TCM， reflect the true feelings of patients， and make up for the limitations of the existing scales of BE. Therefore， based on domestic and international scales， factors of China's national conditions and cultural characteristics of TCM should be considered to develop the scale suitable for Chinese people， which requires the construction of a theoretical model for the combination of disease and syndrome， by taking patients as the center and evaluating the performance and quality of the scale.

XU Fengqin's Experience in Treating Hypertension in the Elderly based on the Theory of “Combination of Disease and Symptoms” / 中医杂志

This paper summarized the clinical experience of XU Fengqin in the treatment of hypertension in the elderly. It is believed that the basic pathogenesis of hypertension in the elderly is liver and kidney depletion， and the key is ascendant hyperactivity of liver yang and spleen failing to transport. Therefore， the theory of “combination of disease and symptoms” is put forward that the four common clinical symptoms of hypertension in the elderly， including morning hypertension， non-dipper hypertension with abnormal circadian rhythm， postprandial hypotension and orthostatic hypotension， should be differentiated and treated with prescription in accordance with the characteristics of the corresponding pathogenesis. Specifically， the pathogenesis of morning hypertension is mainly liver-kidney yin deficiency and ascendant hyperactivity of liver yang， for which the treatment method of enriching liver and boosting kidney， calming the liver and subduing yang is suggested， and Qingxuan Jiangya Decoction （清眩降压汤） in modifications can be used. For non-dipper hypertension with abnormal circadian rhythm， the pathogenesis is mainly phlegm-dampness obstruction and clear yang failing to ascend， and treatment method should be dissolving phlegm and dispelling dampness， calming the liver and extinguishing wind， with Banxia Baizhu Tianma Decoction and Modified Honglong Xiahai Decoction （半夏白术天麻汤合加味红龙夏海汤） in its modifications. Regarding postprandial hypotension and orthostatic hypotension， the pathogenesis is mainly spleen-stomach depletion and clear yang failing to ascend， and thus the method of supplementing the center and boosting qi， raising yang and lifting the sunken is advised with Buzhong Yiqi Decoction （补中益气汤） or Yiqi Congming Decoction （益气聪明汤） in the modifications.

Ideas and Methods of Establishing an Efficacy Evaluation System for Heart Failure：Combining Syndrome in Traditional Chinese and Disease Western Medicine，based on Doctors-patients Shared Reported Outcomes and Using 1+N Model / 中医杂志

Establishing an efficacy evaluation system that conforms to the laws of traditional Chinese medicine （TCM） is one of the keys in the development of TCM. With certain progress in recent years， however， the clinical efficacy evaluation systems or consensus that has been formed are not widely adopted. The main reason is the lack of objectification and standardization of efficacy evaluation， and additionally fixed efficacy evaluation system cannot meet the needs of different clinical research purposes. This paper initially analyzed the development status of clinical efficacy evaluation of heart failure （HF）， and then discussed the specific methods， advantages and difficulties in constructing a TCM clinical efficacy evaluation system for HF using the 1+N model， guided by the idea of combining traditional Chinese and western medicine， disease and syndrome， and based on the shared reported clinical outcomes by doctors and patients. Establishing an efficacy evaluation system that combines disease and syndrome can build a bridge to connect TCM with western medicine； the shared reported clinical outcomes by doctors and patients can reflect the people-centered concept and holism concept in TCM； the 1+N efficacy evaluation model can meet the general clinical research need by constructing one core outcome set （“1”）， and can match different research purposes by adding numbers of other outcomes （“N”）. One difficulty in constructing the TCM efficacy evaluation system for HF is to unify the differentiation standard for TCM syndromes of HF and the standardization to diagnose HF firstly， and then distinguish between syndrome efficacy standards and syndrome diagnostic standards. By constructing a 1+N model-based efficacy evaluation system for HF that not only conforms to the characteristics of TCM itself but also embodies the evidence-based medicine concept in western medicine， it is expected to provide ideas for evaluating clinical efficacy of TCM.

Analysis of Animal Models of Cough Variant Asthma Based on the Characteristics of Clinical Disease and Syndrome of Chinese and Western Medicine / 世界科学技术-中医药现代化

Cough variant asthma(CVA)is a common respiratory disease in clinical practice.The only or main clinical manifestation of CVA is cough.It has similar pathological pathogenesis with asthma,but its pathological changes are sligher than asthma.The research of CVA drugs needs appropriate CVA animal models as the research basis.Based on the characteristics of CVA clinical diseases and syndromes of traditional Chinese and western medicine,combined with the clinical diagnostic criteria of traditional Chinese and western medicine,the CVA animal models are combed and analyzed,in order to provide references for the establishment,evaluation and application of CVA animal models.Chemical induction was used to prepare the commonly used animal models of cough variant asthma,including mice,rats and guinea pigs.The selection of sensitizing agent,adjuvant,activator and cough inducing agent was basically the same in the animal models of cough variant asthma,but there were significant differences in the selection of sensitizing method,sensitizing and stimulating dose,modeling cycle and detection index.Western medicine has clear diagnostic criteria for cough variant asthma,while traditional Chinese medicine can classify cough-variant asthma into different types according to different syndromes.At present,the commonly used animal models of cough variant asthma are highly consistent with the diagnostic criteria of western medicine,but not well consistent with the diagnostic criteria of traditional Chinese medicine,which is insufficient to reflect the symptoms of traditional Chinese medicine.The establishment of CVA animal model combining disease and syndrome,including medical syndromes into the model evaluation criteria,meets the requirements of TCM research on CVA animal model.In model evaluation,behavioral manifestations,HE staining of lung tissue,cell counts in BALF and lung function indicators should be considered in various aspects,and airway excitation test,alveolar lavage fluid eosinophil count,behavioral and other aspects should be distinguished from asthma.

Analysis of the Anastomosis between the Animal Model of Alopecia Areata and the Characteristics of Clinical Disease / 世界科学技术-中医药现代化

In this study,the existing animal models of alopecia areata were systematically summarized based on literature review and disease and syndrome characteristics assignment method,and the clinical anastomosis was analyzed.The results showed that cell induction and skin transplantation had a high anastomosis with the clinic,and the anastomosis was as high as 80%.The anastomosis between imiquimod cream and cyclophosphamide induced alopecia areata was 72%.C3H/HeJ mice and C57BL/6 mice were selected as the first choice in terms of the pathogenesis of alopecia areata disease,pathogenic factors,replicability,convenience and practicability of the model.Other SCID mice,B6.KM-AA mice,SD rats and BALB/c mice can be selected appropriately according to the content and period of the experimental study of alopecia areata.It is found that the existing models of alopecia areata mainly rely on Western medicine,lack of pathogenic factors of traditional Chinese medicine,and the model of combining disease and syndrome of alopecia areata is not widely used in practice.Based on this,it is suggested that the animal model of"combination of disease and syndrome"should be considered in the subsequent construction of alopecia areata model to make it more suitable for clinical characteristics of disease and syndrome.We can add the relevant indicators of different syndrome types of liver and kidney insufficiency,blood stasis and maoqiao,blood deficiency and blood heat and other pathogenic factors,and add the apparent indicators of animal mental state,diet and water intake,behavior,etc.,to improve the animal model of alopecia areata which is highly consistent with the clinical characteristics of traditional Chinese and western medicine.

Research Progress of Henoch-Schonlein Purpura Experimental Animal Model Based on the Combination of Disease and Syndrome / 世界科学技术-中医药现代化

Henoch-Schonlein purpura(HSP)combination of disease and syndrome model has short modeling time,strong operability and high repeatability,which is more suitable for the research of TCM and integrated traditional Chinese and Western medicine.However,there are still the following deficiencies:①Lack of model evaluation criteria.What criteria should be used to establish successful animal models and whether the diagnostic criteria for human HSP are of reference significance?In the future,we should cooperate with Chinese veterinary medicine to carry out omics studies at various levels including genome,proteome and metabolome by combining the unique information of animals with the theories and methods of systems biology,and formulate the criteria for determining HSP animal models through data integration.In terms of syndrome:all the existing models are the model of animal stasis and heat syndrome caused by gavage of heat-induced drugs,but there is no criterion for the successful establishment of syndrome.In the future,it can be combined with ethanol,high-fat diet and fatty milk on the basis of simple heat-induced drug gavage,and compare different combination groups.In the aspect of syndrome evaluation,the four-diagnosis quantitative syndrome differentiation system was introduced to establish the TCM syndrome model evaluation scale of Henoch-Schonlein Purpura's stasis and heat.② There are great differences between animal model and clinical practice,and the reproducibility is low.At present,the combined models of disease and syndrome focus on purpura nephritis,and in the establishment of the animal model of pure dermal allergic purpura,the skin damage rate of the animal model(such as purpura,purpura)is low.In the future,we can learn from the modeling method of other allergic diseases,and increase the excitation times in the operation steps,in order to improve the skin damage rate.③All the existing HSP models are the syndrome model of blood stasis and heat first,and the disease model of HSP is reconstructed.However,the actual disease occurrence is the syndrome in the disease,and the syndrome is the pathological summary at a certain stage in the development of the disease,which is dynamic.In the future,the intervention operation of the etiology and syndrome should be carried out on experimental animals at the same time,so as to build a stable time window for the combination of disease and syndrome.

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence / 中国实验方剂学杂志

ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

Establishment and Evaluation of Animal Models of Chronic Fatigue Syndrome / 中国实验方剂学杂志

Chronic fatigue syndrome （CFS） is a heterogeneous disease with dysfunction in multiple systems and multiple organs. Its etiology and pathogenesis have not been fully clarified， and its treatment also lacks specificity. The key to studying CFS is developing animal models that reflect the underlying mechanisms and etiology of CFS. The existing CFS modeling methods are complicated and not unified. By sorting out relevant literature，the present study evaluated the modeling methods，modeling standards，mechanisms， and clinical coincidence of the immune model，the stress model， and the disease-syndrome combination model in traditional Chinese medicine （TCM）. The immune model is mainly constructed from the perspective of pathophysiology， with easy operation and wide investigation， which can simulate the pathological characteristics of CFS to ensure pathogenesis research，but the experimental repeatability is general. Stress modeling is a common method for a variety of neuropsychiatric diseases，including CFS. Many different stressors can be employed to investigate the etiology of CFS， but their effects are unpredictable. Compared with the two western medicine models mentioned above，the TCM disease-syndrome combination model integrates modern medicine with TCM theory，with high clinical coincidence and great practical value. However，the TCM disease-syndrome combination model of CFS is still in the exploratory stage with a few types of models，which needs to be further improved， aiming to establish scientific，reasonable，simple， and efficient animal models to provide support for exploring the etiology，pathogenesis， and new treatment ideas of CFS.

Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom / 中国中药杂志

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 μg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

Establishment and evaluation of a rat model of coronary microvascular disease with qi deficiency and blood stasis syndrome / 中国实验动物学报

Objective The incidence of coronary microvascular disease(CMVD)is increasing annually.According to traditional Chinese medicine(TCM),CMVD belongs to the category of"collaterals",and qi deficiency and blood stasis are the main syndrome type of CMVD.Notably however,no studies have reported on the use of animal models of CMVD with qi deficiency and blood stasis.The current study therefore aimed to establish and evaluate a rat model of CMVD with qi deficiency and blood stasis syndrome.Methods Forty-five male SD rats were divided randomly into sham group,CMVD group,and CMVD + QXXY group(n = 15 rats per group).Rats in the CMVD + QXXY group were randomly deprived of sleep for 14～16 h/day for 6 weeks,and the model of qi deficiency syndrome was established.Animals in the sham group and the CMVD group were fed normally for 6 weeks.After 6 weeks,rats in the CMVD and CMVD + QXXY groups were anesthetized,their chests were opened,and embolic microspheres(40～120 μm)were injected into the left ventricle.Rats in the sham group underwent thoracotomy without injection of embolic microspheres.On day 7 after operation,relevant detection indicators were measured in each group.Results Compared with the sham group,the CMVD group showed a significant decrease in left ventricular ejection fraction and left ventricular shortening rate,while the activities of creatine kinase MB isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were significantly increased.Heart function,hemorheology,myocardial enzyme index,and the degree of myocardial cell damage differed significantly between the CMVD + QXXY group compared with the sham group.Conclusions A rat model of CMVD + qi deficiency + blood stasis syndrome can be successfully established by sleep deprivation combined with intraventricular injection of embolic microspheres.This model will be suitable for the study of the pathogenesis of CMVD and the mechanisms of TCM.

[Guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology (FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia].

This paper discussed the guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia(HPRL). FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) concentrates on the disease entities, main symptoms, pathogenesis, and syndrome differentiation, based on which the prescriptions are prescribed. This reflects the "disease-syndrome-symptom" mode, with the core lying in the "combination of disease with syndrome". The contained Discussion on Menstruation Regulation(Tiao Jing Pian) and Discussion on Getting Pregnant(Zhong Zi Pian) have important reference significance for later doctors in the diagnosis and treatment of inferti-lity, and many prescriptions are still in use due to good effects. It is believed in traditional Chinese medicine(TCM) that HPRL results from kidney deficiency and liver depression, among which kidney deficiency is the main cause. Liver depression accelerates the onset of HPRL, so the kidney-tonifying and liver-soothing herbs were mainly selected. The "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) sheds enlightenment on the diagnosis and treatment of ovulation infertility caused by HPRL, in that it is not confined to disease entity and syndrome type. The integration of "disease-syndrome-symptom" highlights the main complaint of patients and emphasizes the main pathogenesis, thus giving full play to the overall advantage of syndrome differentiation. For multiple diseases in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) such as infertility due to liver depression, infertility due to obesity, delayed menstruation, and irregular menstruation, although the typical lactation symptom of HPRL is not mentioned, the medication can still be determined according to the chief complaint, syndrome type, and symptoms and signs, making up for the defects of excessive reliance on serum biochemical indicators in modern Chinese medicine. We should learn its diagnosis and treatment thoughts of paying attention to liver, spleen, kidney, and heart, holism, and strengthening body resistance to eliminate pathogenic factors.

Guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology (FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia / 中国中药杂志

This paper discussed the guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia(HPRL). FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) concentrates on the disease entities, main symptoms, pathogenesis, and syndrome differentiation, based on which the prescriptions are prescribed. This reflects the "disease-syndrome-symptom" mode, with the core lying in the "combination of disease with syndrome". The contained Discussion on Menstruation Regulation(Tiao Jing Pian) and Discussion on Getting Pregnant(Zhong Zi Pian) have important reference significance for later doctors in the diagnosis and treatment of inferti-lity, and many prescriptions are still in use due to good effects. It is believed in traditional Chinese medicine(TCM) that HPRL results from kidney deficiency and liver depression, among which kidney deficiency is the main cause. Liver depression accelerates the onset of HPRL, so the kidney-tonifying and liver-soothing herbs were mainly selected. The "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) sheds enlightenment on the diagnosis and treatment of ovulation infertility caused by HPRL, in that it is not confined to disease entity and syndrome type. The integration of "disease-syndrome-symptom" highlights the main complaint of patients and emphasizes the main pathogenesis, thus giving full play to the overall advantage of syndrome differentiation. For multiple diseases in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) such as infertility due to liver depression, infertility due to obesity, delayed menstruation, and irregular menstruation, although the typical lactation symptom of HPRL is not mentioned, the medication can still be determined according to the chief complaint, syndrome type, and symptoms and signs, making up for the defects of excessive reliance on serum biochemical indicators in modern Chinese medicine. We should learn its diagnosis and treatment thoughts of paying attention to liver, spleen, kidney, and heart, holism, and strengthening body resistance to eliminate pathogenic factors.

Research Progress of Digestive System Disease and Syndrome Combined Animal Model and Traditional Chinese Medicine Target Intervention： A Review / 中国实验方剂学杂志

Reflux esophagitis （liver-stomach disharmony， Spittoon-Qi interties， Qi and blood stasis syndrome， turbid poison intrinsic） and nonalcoholic fatty liver disease （liver depression， spleen deficiency， phlegm and blood stasis syndrome， hot and humid embodiment， phlegmy wet resistance） and functional dyspepsia （liver depression syndrome， liver stomach with spleen deficient， spleen deficiency cold syndrome， in a word， fever） is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine（TCM） effect and the foundation of the development of new preparations. At the same time， mastering the complex relationship network among disease， syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases， the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path， multi-target， multi-dimension and multi-level. Therefore， this article through the literature review， summarizes the reflux esophagitis， nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM， so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research， and the basic research of TCM prescription and achievements provide methodological guidance.

Research Progress of Digestive System Disease and Syndrome Combined Animal Model and Traditional Chinese Medicine Target Intervention： A Review / 中国实验方剂学杂志

Reflux esophagitis （liver-stomach disharmony， Spittoon-Qi interties， Qi and blood stasis syndrome， turbid poison intrinsic） and nonalcoholic fatty liver disease （liver depression， spleen deficiency， phlegm and blood stasis syndrome， hot and humid embodiment， phlegmy wet resistance） and functional dyspepsia （liver depression syndrome， liver stomach with spleen deficient， spleen deficiency cold syndrome， in a word， fever） is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine（TCM） effect and the foundation of the development of new preparations. At the same time， mastering the complex relationship network among disease， syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases， the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path， multi-target， multi-dimension and multi-level. Therefore， this article through the literature review， summarizes the reflux esophagitis， nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM， so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research， and the basic research of TCM prescription and achievements provide methodological guidance.