1.Astragali Radix-Curcumae Rhizoma Inhibits Metastasis of Lewis Lung Cancer in Mice via C5a/NETs Pathway
Peiyu TIAN ; Hongyang YU ; Xiao LI ; Luhang YU ; Ziqiao YAN ; Yongqi DOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):27-36
ObjectiveTo explore the mechanisms of Astragali Radix-Curcumae Rhizoma (HQ-EZ) in alleviating hypercoagulability and inhibiting tumor growth and metastasis by modulating the formation of neutrophil extracellular traps (NETs) via the complement component 5a (C5a)/C5a receptor (C5aR) pathway. MethodForty male C57BL/6 mice were randomized into four groups: Blank, model, HQ-EZ (8.2 g·kg-1), and PMX53 (1 mg·kg-1). The mouse model of Lewis lung cancer was established in other three groups except the blank group. Mice were administrated with corresponding drugs from day 3 after modeling. Specifically, the HQ-EZ decoction was administrated for 14 consecutive days, while intraperitoneal injection of PMX53 was implemented on days 3, 6, 9, 12, and 15. Mouse body weight and tumor diameter were measured every two days. On the next day of the last administration, lung microCT was performed to observe the tumor metastasis in vivo. Blood samples were collected from the eyeball after anesthetization, and tumor and lungs were collected after the mice were sacrificed. Tumor weight was measured to calculate the tumor growth inhibitory rate. Enzyme-linked immunosorbent assay was employed to measure the levels of C5a, neutrophil elastase (NE), citrullinated histone-H3 (Cit-H3), myeloperoxidase (MPO), matrix metallopeptidase-9 (MMP-9), NETs, von Willebrand Factor (vWF), tissue factor (TF), and P-selectin in the serum and tumor tissue. Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was conducted to assess apoptosis in the tumor tissue. Hematoxylin-eosin staining was conducted to observe lung metastasis, and immunofluorescence (IF) was employed to observe the expression of NETs in the tumor tissue. Western blot was employed to determine the protein levels of C5aR, MPO, and Cit-H3 in the tumor tissue. ResultCompared with the blank group, the model group had nodules in the lung, increased areas with low X-ray transmittance, appearance of nodular foci and multiple hemorrhagic foci in the lungs, and darkening lung color. Furthermore, the modeling elevated the serum levels of C5a, NETs and related proteins, vWF, TF, and P-selectin (P<0.01). Compared with the model group, HQ-EZ and PMX53 reduced the lung metastases, areas with low X-ray transmittance, and nodules in the lungs and lightened the lung color. Compared with the model group, the two drug intervention groups showed flat tumor growth curves, decreased tumor weight (P<0.01), increased apoptosis of tumor cells (P<0.01), lowered levels of C5a, NETs and related proteins, vWF, TF, and P-selectin both in the serum and tumor tissue (P<0.05), and down-regulated protein levels of C5aR, MPO, and Cit-H3 (P<0.05). ConclusionHQ-EZ inhibited the expression of NETs by suppressing the C5a/C5aR pathway, thereby alleviating hypercoagulability and inhibiting tumor growth and metastasis.
2.Application of optimized Asia-Pacific colorectal screening scoring system in the screening of colorectal neoplasms
Na HE ; Gong FENG ; Jianhua DOU ; Guangbo TANG ; Meirui QIAN ; Yongqi LI ; Kaichun WU
Chinese Journal of Digestion 2020;40(6):393-399
Objective:To explore the optimization strategy of the Asia-Pacific colorectal screening (APCS) scoring system in the screening of colorectal neoplasms.Methods:From February to Decomber in 2016 and March to December in 2018, at Xijing Hospital of Air Force Military Medical University and the First Affiliated Hospital of Xi′an Medical University, patients who received opportunistic screening colonoscopy were enrolled. Before colonoscopy, the APCS score (low-risk zero to one points, medium-risk two to three points and high-risk four to seven points), body mass index (BMI), fecal occult blood test (FOBT) and plasma methylated Septin9 gene ( mSEPT9) of all patients were detected and recorded. The results of colonoscopy and biopsy pathology were taken as the gold standard, the efficacies of the above methods in screening colorectal neoplasms were compared to determine and optimize the screening efficiency of APCS scoring system. Chi-square test was used for statistical analysis. Results:A total of 494 patients were screened, of whom 133 cases were diagnosed with colorectal polyps, including 86 cases of colorectal adenomatous polyps (82 cases of non-progressive adenoma, and four cases of advanced-adenoma), and 47 cases of non-adenomatous polyps. According to the APCS score, the detection rate of colorectal adenomatous polyps of the high-risk group (33.3%, 33/99) was 2.02 and 3.76 times higher than those of the medium-risk group (16.5%, 39/237) and low-risk group (8.9%, 14/158), respectively (both Bonferroni correction test, both P<0.016). The detection rate of colorectal adenomatous polyps of patients with BMI>23.9 kg/m 2 was significantly higher than that of patients with BMI≤23.9 kg/m 2 (22.2%, 59/266 vs. 11.8%, 27/228), and the difference was statistically significant ( χ2=9.126, P=0.003). There was no statistically significant difference in the detection rate of colorectal adenomatous polyps between patients with positive- mSEPT9 expression and patients with negative- mSEPT9 expression (22.4%, 15/67 vs. 17.3%, 47/271) ( χ2=0.913, P=0.378). Among 158 low and medium risk patients (APCS score≤three points) who underwent simultaneous BMI measurement, FOBT and plasma mSEPT9 test, the detection rate of colorectal adenomatous polyps in patients with BMI>23.9 kg/m 2 was higher than that in patients with BMI≤23.9 kg/m 2 (17.8%, 16/90 vs. 5.9%, 4/68), and the difference was statistically significant ( χ2=4.957, P=0.030). The redetection efficacy of colorectal adenomatous polyps in patients with BMI>23.9 kg/m 2 and FOBT-positive was higher than that in patients with BMI≤23.9 kg/m 2 and FOBT-negative (28.1%, 9/32 vs. 8.0%, 4/50) and the difference was statistically significant ( χ2=5.942, P=0.027). In addition, the redetection rate of colorectal adenomatous polyps of patients with positive expression of FOBT and plasma mSEPT9 was also higher than that of patients with negative expression (5/14 vs. 12.9%, 12/93), and the difference was statistically significant ( χ2=4.738, P=0.045). Conclusions:When the APCS scoring system is used for sequential screening of colorectal tumors, the optinal choice of BMI replacement or combined with FOBT can improve the patients′ compliance and screening efficiency, which has significant clinical significance and promotion value in the early diagnosis and treatment of colorectal neoplasms.
3.Induction of Astragalus Polysaccharides on Differentiation of Rat Bone Marrow ;Mesenchymal Stem Cells
Yongqi LIU ; Jingya LI ; Ling CAI ; Juanjuan DOU
Chinese Journal of Information on Traditional Chinese Medicine 2014;(6):60-64
Objective To investigate the effect of astragalus polysaccharides (APS) on the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) to neurones, adipocytes, osteoblasts and chondrocytes, and provide basis for the development of effective and low toxic differentiation inducing agents. Methods BMSCs were isolated from SPF Wistar rats, purified, expanded and cultured to family 3. The appropriate concentration of APS was filtered out by MTT assay. The F3 cells were randomly divided into control group and induced group (neural induction, adipogenic induction, osteogenic induction, cartilage induction). The effects of APS and classical chemical drugs on differentiation were measured by toluidine blue, oil red o and alizarin red staining. The protein expression of NSE, LPL, collagen Ⅰ and collagen Ⅱ were examined by Western Blot. Results MTT assay showed that 1 g/L APS promoted the proliferation better than other concentrations especially in 48 hours. The morphologic change of the cell from BMSCs was uniformly positive to toluidine blue staining, and was negative to oil red o and alizarin red staining. Western blot showed that the protein expression of the cell from BMSCs was positive for NSE but negative for LPL, collagen Ⅰ and collagen Ⅱ. Conclusion BMSCs induced by APS can differentiate to neurone and fail to differentiate to adipocytes, osteoblasts and chondrocytes in vitro.
4.Effects of Bushen Huoxue Granule on motor function in patients with Parkinson's disease: a multicenter, randomized, double-blind and placebo-controlled trial.
Minghui YANG ; Min LI ; Yongqi DOU ; Yi LIU ; Xiaodong LUO ; Jianzong CHEN ; Hengjun SHI
Journal of Integrative Medicine 2010;8(3):231-7
The main clinical symptoms of Parkinson's disease (PD) are resting tremor, muscle rigidity, bradykinesia, and so on. There is no effective treatment for PD yet, and dyskinesia symptoms affect the life qualities of PD patients. The therapy used for reinforcing kidney and activating blood circulation in treatment of PD can achieve good clinical effects.
5.Efficacy of Liangxue Jiedu Huoxue Decoction in prevention of radiation pneumonitis: a randomized controlled trial.
Chun XIAO ; Huijuan DING ; Linchun FENG ; Baolin QU ; Yongqi DOU
Journal of Integrative Medicine 2010;8(7):624-8
Background: Radiation pneumonitis is one of the most common complications during radiotherapy of thoracic tumors. It impacts the quality of life of the patients and has life-threatening danger. However, there is a lack of drugs for prevention and treatment of this disease. Objective: To evaluate the efficacy of Liangxue Jiedu Huoxue Decoction, a compound traditional Chinese herbal medicine, in prevention of radiation pneumonitis. Design, setting, participants and interventions: A prospective randomized clinical study was conducted. A total of 100 patients diagnosed with lung cancer from Department of Radiotherapy, Chinese PLA General Hospital, who were planning to receive radiotherapy, were randomly assigned into treatment group and control group, with 50 patients in each group. In the treatment group 3 cases were lost to follow-up and one case was excluded, while in the control group 6 cases were lost to follow-up and 2 cases were excluded. Patients in the treatment group were treated with Liangxue Jiedu Huoxue Decoction in addition to radiotherapy, while patients in the control group were treated with radiotherapy alone. Main outcome measures: The incidence rates of radiation pneumonitis in the two groups were calculated. Acute radiation injury scoring criteria by Radiation Therapy Oncology Group (RTOG), clinical-radiographic-physiologic (CRP) score system, and Karnofsky Performance Status Scale (KPS) were used to evaluate the status of the patients. Results: The incidence rate of radiation pneumonitis was lower in the treatment group than in the control group (13.04% versus 33.33%, P<0.05). According to the RTOG scale, the extent of lung injury was improved in the treatment group as compared with that in the control group (P<0.05). The CRP score in the treatment group was significantly lower than that in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.05). Conclusion: Liangxue Jiedu Huoxue Decoction can decrease the incidence rate of radiation pneumonitis, reduce the extent of the lung injury, alleviate the symptoms of radiation pneumonitis, and improve life quality of the patients.
6.Effects of yichan tang on rotatory behavior, substance nigra cells and neurotransmitter of rats with Parkinson disease
Yongqi DOU ; Minghui YANG ; Wei WANG ; Yi LIU
Chinese Journal of Tissue Engineering Research 2006;10(31):168-171
BACKGROUND: Parkinson disease (PD) not only influences motor function, also affects sensation and cognition. Treatment with dopamine can only control symptom and has well side effect; however, yichan tang has great effect on treating PD in clinic.OBJECTIVE: To observe the effect of yichan tang on praxiological behavior, catecholamines substance in cerebral tissue and substantia nigra nerve cells of PD rats and analyze its effective mechanism.DESIGN: Randomized control animal study and single-blind evaluation.SETTING: Department of Traditional Chinese Medicine of General Hospital of Chinese PLA.MATERIALS: A total of 120 female SD rats weighing 180-200 g were selected in this study. Seventy modeling PD rats were randomly divided into saline group (n=30) and yichan tang group (n=40) according to digital table. Another 30 non-modeling rats were regarded as normal control group. Yichan tang was made of 15 g shanyurou, 15 g shichangpu, 10 g xianlingpi, 10 g roucongrong, 15 g gouqizi, 15 g danshen and 8 g wugong,etc., and provided by Dispensary of Chinese herb of General Hospital of Chinese PLA. Drug was decocted for 30 minutes to filter the solution and then concentrated into decoction including 1.0 g/mL raw materials.METHODS: The experiment was carried out at the Animal Laboratory of General Hospital of Chinese PLA from September to December 2001. PD rat model were established with 6-hydroxy-dopa to observe behavior of rats.The administration of rats (body mass/kg) in yichan tang group was 10 times as the administration of the adults (60 kg) (5 g/kg). Rats were perfused once a day and weighted once a week. The dosage of administration was regulated as the body mass changing, and the administration lasted for 8 weeks. Rats in saline group and normal control group were perfused with the same volume of saline as the criteria of body mass. Rotatory behaviors of rats in normal group, saline group (model group before administration)and yichan tang group were observed before administration and at 5, 6, 7 and 8 weeks after administration. Changes of content of catecholamines in extracellular fluid of cerebral tissue were measured with micro-dialysis technique and high performance liquid chromatography (HPLC), meanwhile, changes of substantia nigra nerve cells on both sides of corpus striatum were observed under 20-time and 40-time optic microscopes.MAIN OUTCOME MEASURES: Effect of yichan tang on medium of cranial nerve of PD rats; changes of substantia nigra nerve cells on both sides of corpus striatum with optic microscope and electron microscope; evaluation of yichan tang.RESULTS: Among 100 rats, 6 rats in yichan tang group died because of failure perfusion, 5 in saline group and 2 in normal control group. Therefore, 87 rats were involved in the final analysis. ① At 5, 6, 7 and 8 weeks after treatment, rotatory times within 40 minutes were all shorter in yichan tang group than those in saline group [(112.34±33.36), (91.16±73.06),(72.05±20.77), (61.63±17.93), (340.90±52.97) times, P < 0.01]. ② Levels of 3,4-dihydroxybenzene acid, homovanilic acid, dopamine and 5-serotonin on the injured side were lower than those on the uninjured side (P < 0.05-0.01). After treatment, levels of mediums mentioned above were higher in yichan tang group than those in saline group (P < 0.05-0.01); however,there were no significant differences of mediums on the uninjured side in the three groups (P > 0.05). ③ Pathological observation: Amount of substantia nigra nerve cells on the injured side was more in yichan tang group than that in saline group; moreover, volume of neurons was full, structure was clear, and values of Golgi complex and mitochondria were close to the normals.CONCLUSION: Yichan tang can relieve injured degrees of substantia nigra nerve cells, facilitate the repair, increase the content of endogenetic catecholamines in cerebral tissue, and improve rotatory behavior of PD rats.
7.Study on dose-effect relationships in prevention and treatment of radiation-induced lung injury of rat with blood-cooling and blood flow-promoting drugs(凉血活血方)
Minghui YANG ; Yongqi DOU ; Mingxiong LIN ; Linchun FENG ; Yi LIU ; Yan YANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2006;0(01):-
Objective To evaluate the therapeutic effects and dose-effect relationships of different doses of the blood-cooling and blood flow-promoting drugs(凉血活血方) on radiation-induced lung injury of rat.Methods Seventy-two Wistar rats were randomly allocated into four groups: irradiation group(group A),small-dose group(group B,9 g?kg-1?d-1),middle-dose group(group C,18 g?kg-1?d-1) and high-dose group(group D,36 g?kg-1?d-1).All groups were repeatedly exposed to small dose of X-ray in the right hemi-thorax,and then the mice were sacrificed at different time points.The living animal features,the macro-changes of lung were observed,and pulmonary histopathological changes in all the groups were investigated,and the results of observation were compared.Results The symptoms of red patches around the nose and dry stool in groups C and D were less than those of groups A and B.After 26 weeks,lung coefficient in groups B,C and D was the same as that in group A,but right lung wet weights and lung coefficients at each time point in groups B,C and D were significantly lower than those in group A,and during 5th week,the right lung wet weights in groups C and D were obviously lower than the weight in group B(all P
8.Effects of Yichan decoction(抑颤汤) on dopamine receptors and neurotensin in cerebral tissue of rats with Parkinson's disease
Minghui YANG ; Haiming WANG ; Yi LIU ; Yongqi DOU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2006;0(02):-
Objective To explore the mechanism of Yichan decoction(抑颤汤) in treatment of Parkinson′s disease(PD).Methods A PD rat model was made by direct injection of 6-hydroxydopamine(6-OHDA) into the brain to destruct the compact part of substantia nigra(SNC).One hundred Sprague-Dawley(SD) rats were randomly divided into a normal control group,a PD model group and a Yichan decoction treatment group and they were treated for 8 weeks.The rats′ behavior pattern changes were observed before treatment and from 5th weeks after treatment.The changes in the dissociation constant(Kd) and maximum number of binding sites(Bmax) of dopamine(DA) receptors,and neurotensin-immunoreactive(NT-IR) in substantia nigra after treatment were determined by using the technique of radioimmunity.Results Yichan decoction could markedly improve the rotation of PD model rats and decrease the average number of rotation from(349.56?62.28) circle/40 minutes to(61.63?17.93) circle/40 minutes(P
9.Measurement scale of traditional Chinese medical syndrome of sub-health state
Minghui YANG ; Shaodan LI ; Yongqi DOU ; Dengfeng ZHOU ; Fan ZHANG
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(07):-
Objective:To study and design measurement scale which can judge and survey sub-health state and itscharacteristic of TCM syndrome.Methods:Making use of methods of scale technique,literature research,expertise consultation et al,based on TCM theory,via conceptualization and operation of sub-health and TCM syndrome,forming structure and type of scale,establishing item pool and results,and then through item selection,assessment of validity and reliability of pre-investigation,making the measurement scale.Results:The scale is made up of 4 parts:body function state,psychological function state,social function state and particular state of TCM.The 4 parts are divided into 15 sorts,including 120 items.Conclusion:The scale contributes much to the diagnosis of sub-health state and the clari cation of clinical manifestations,features,distributions of TCM syndrome of public of sub-health,which is one of the most important methods for investigating TCM syndrome of sub-health state.
10.Experimental study on TCM symptomatological and developmental characteristics of rats with radiation-induced lung injury
Yongqi DOU ; Minghui YANG ; Mingxiong LIN ; Yi LIU ; Qian ZANG
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(06):-
Objectives:To explore the possibility of using experimental animal models as a new means for studying the pathogenesis and symptomatologic development of radiation-induced lung injury,and provide theoretical and experimental evidences for early prevention and treatment with the traditional Chinese medicine.Methods:80 female Wistar rats were divided randomly into the model group and control group with 40 rats in each group respectively.The rats in model group were anesthetized and fixed,and a 2cm?3cm area of the right lungs received 6mV X-ray radiation at 3Gy?2/w and a maximal 10/5w.Eight rats randomly selected from each group were sacrificed at the end of weeks of 3,5,8,12 and 26.Diagnostic techniques of TCM were employed to analyze symptomatological and developmental characteristics of TCM in radiation-induced lung injury during exposure by dynamic examination and comparison of living rats,gross lung samples and tissue sections.Results: Signs and symptoms including redness around nose and eyes,yellowish secretion,tachypnea,dry stool,lethargy,sluggishness, inactiveness were observed in model group in early stage of radiation exposure,which consistent with dominant heat in the interior and primordial qi exhaustion syndrome.Swollen lungs,bright redness on surface and red bleeding patches were observed in early stage of radiation;microscopic examination showed interstitial tissues,and readily visible congestion,hemorrhage and edema of pulmonary interstitial tissues,consistent with damaged blood collaterals by heat and blood escaping circulation syndrome.In the later stage of radiation exposure,the lungs showed dark appearance,apparent purple petechia,hard texture and poor elasticity.Microscopic examination showed remote hemorrhage foci,pulmonary capillary stasis or closure,and focal fibrotic clumps,consistent with obstruction of collaterals by blood stasis syndrome.No abnormal changes were observed in the control group.Conclusions:Animal experiments can redeem the clinical inadequacy of traditional inspection,auscultation and olfaction,interrogation and feeling pulse and palpation diagnostic techniques,modern pathological methods can be utilized to study symptomatology of traditional Chinese medicine.Symptomatological and developmental characteristics of'heat toxin impairment in radiation-induced lung injury characterized by heat damaging pulmonary collateral syndrome in early stage and pulmonary collateral stagnation syndrome in the advanced stage'can be revealed at living organism,gross lung sample and microscopic pulmonary tissue levels,thus providing theoretical basis for early prevention and treatment of radiation-induced lung injury using'cooling blood to remove apthogenic heat'.

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