1.Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation.
Hang ZHAO ; Xin MA ; Hao WANG ; Xiao-Jie DING ; Le KUAI ; Jian-Kun SONG ; Zhan ZHANG ; Dan YANG ; Chun-Jie GAO ; Bin LI ; Mi ZHOU
Journal of Integrative Medicine 2025;23(3):309-319
OBJECTIVE:
To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD).
METHODS:
The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4+ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis.
RESULTS:
POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA.
CONCLUSION
Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy*
;
Animals
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Humans
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Cell Differentiation/drug effects*
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Phosphorylation/drug effects*
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Mice
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Th2 Cells/drug effects*
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Keratinocytes/drug effects*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Calcitriol/analogs & derivatives*
2.Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma
Tian LU ; Hao MI ; Dan-Dan ZHAO ; Shui-Ge YANG ; Yun-Wen BU ; Fang ZHANG ; Wen-Ming CHEN ; Dao-Ping SUN
Journal of Experimental Hematology 2024;32(2):458-465
Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell<0.1 × 109/L,n=34)and high B-cell count group(B cell≥0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.
3.Preparation of curcumin-loaded PLGA nanoparticles and their effects on promoting wound healing
Lan ZOU ; Jin-jin XIE ; Ru-jing WANG ; Huan YANG ; Xin DU ; Dan-dan MI ; San-jun SHI
Chinese Traditional Patent Medicine 2024;46(12):3930-3937
AIM To prepare curcumin-loaded poly (D,L-lactide-co-glycolide) acid (PLGA) nanoparticles,and to investigate their effects on promoting wound healing.METHODS Phacoemulsification method was adopted in the preparation of PLGA nanoparticles.With lactic acid-glycolic acid ratio,surfactant type and concentration and PLGA consumption as influencing factors,encapsulation efficiency,drug loading,particle size and PDI as evaluation indices,the preparation process was optimized by single factor test.The morphology was observed under transmission electron microscopy,after which the in vitro drug release was determined by dialysis bag method,the optical properties were investigated by fluorescence spectroscopy,and the effects on promoting wound healing of mouse skin.RESULTS The optimal conditions were determined to be 50∶50 for lactic acid-glycolic acid ratio,60 mg for PLGA consumption,and 3% for surfactant (PVA) concentration.The obtained PLGA nanoparticles with spherical core-shell structure demonstrated the average particle size,PDI,Zeta potential and accumulative release rate within 168 h of (149.70±7.27) nm,0.28±0.04 and (-10.18±1.00) mV and (39.21±1.44)%,respectively,which displayed typical aggregation-induced emission property,excitation wavelength-dependent property and optical stability.Compared with the PBS group,PBS+illumination group,curcumin+illumination group and preparation group,the preparation+illumination group exhibited increased wound healing rate (P<0.05,P<0.01) and reduced wound epidermal thickness (P<0.05,P<0.01).CONCLUSION Curcumin-loaded PLGA nanoparticles show good optical properties,which can promote the wound healing of mouse skin when combined with photodynamic therapy.
4.Preparation of curcumin-loaded PLGA nanoparticles and their effects on promoting wound healing
Lan ZOU ; Jin-jin XIE ; Ru-jing WANG ; Huan YANG ; Xin DU ; Dan-dan MI ; San-jun SHI
Chinese Traditional Patent Medicine 2024;46(12):3930-3937
AIM To prepare curcumin-loaded poly (D,L-lactide-co-glycolide) acid (PLGA) nanoparticles,and to investigate their effects on promoting wound healing.METHODS Phacoemulsification method was adopted in the preparation of PLGA nanoparticles.With lactic acid-glycolic acid ratio,surfactant type and concentration and PLGA consumption as influencing factors,encapsulation efficiency,drug loading,particle size and PDI as evaluation indices,the preparation process was optimized by single factor test.The morphology was observed under transmission electron microscopy,after which the in vitro drug release was determined by dialysis bag method,the optical properties were investigated by fluorescence spectroscopy,and the effects on promoting wound healing of mouse skin.RESULTS The optimal conditions were determined to be 50∶50 for lactic acid-glycolic acid ratio,60 mg for PLGA consumption,and 3% for surfactant (PVA) concentration.The obtained PLGA nanoparticles with spherical core-shell structure demonstrated the average particle size,PDI,Zeta potential and accumulative release rate within 168 h of (149.70±7.27) nm,0.28±0.04 and (-10.18±1.00) mV and (39.21±1.44)%,respectively,which displayed typical aggregation-induced emission property,excitation wavelength-dependent property and optical stability.Compared with the PBS group,PBS+illumination group,curcumin+illumination group and preparation group,the preparation+illumination group exhibited increased wound healing rate (P<0.05,P<0.01) and reduced wound epidermal thickness (P<0.05,P<0.01).CONCLUSION Curcumin-loaded PLGA nanoparticles show good optical properties,which can promote the wound healing of mouse skin when combined with photodynamic therapy.
5.Development and reliability-validity testing of Chinese urban version of perinatal depression screening scale
Shan ZHANG ; Xueyun GAO ; Meina XU ; Jing LI ; Chengyin DOU ; Qinghong LI ; Dan ZHANG ; Rufang CHEN ; Shan WANG ; Yang MI ; Zhongliang ZHU ; Hui LI
Chinese Journal of Perinatal Medicine 2024;27(12):1042-1048
Objective:To develop a perinatal depression screening scale for Chinese urban version and test its reliability and validity.Methods:Naturally conceived women who were≥12 weeks of gestation and had regular prenatal examinations or delivered within four weeks in Xi'an and Foshan were recruited using convenience sampling. Initial entries were created through clinical interviews and expert validation of 50 of these pregnancies. Further item screening and testing for reliability and validity using correlation analysis, critical ratio method, homogeneity test, and factor analysis were performed. The final questionnaire was formed and then used to test the subjects. Fifty women who had completed the questionnaire effectively were selected for retesting 10 to 15 days after the initial evaluation. A structural equation model was constructed using the Edinburgh Postpartum Depression Scale (EPDS) as the reference criterion to conduct the scale's exploratory and confirmatory factor analysis. The receiver operating characters curve was used to determine the cut-off point of the scale.Results:(1) 1 300 questionnaires were issued, and 1 049 valid questionnaires were received with a recovery rate of 80.7%. Among them, 601 were used for exploratory and correlation analysis, and 448 were used for confirmatory factor analysis. (2) The initial entries of the scale totaled 63. After eliminating indicators that did not meet the requirements for item analysis, the final scale consisted of 22 entries in total. The final scale consisted of six dimensions, including "abnormal mood", "loss of interest and pleasure," "sleep disorder," "self-blame and guilt," "decline in conscious thought ability," and "lack of energy". (3) The correlation coefficients between the above six dimensions and EPDS were 0.609, 0.322, 0.423, 0.522, 0.545, and 0.516, respectively. The one between the total scale and EPDS was 0.715 (all P<0.01). (4) The confirmatory factor analysis of each model and the scale showed an acceptable fit and a stable factor structure with indices Chi-square/degrees of freedom =2.504, square root of approximation error=0.058, standardized root mean square residual=0.048, comparative fit index=0.925, Tueker-Lewis index=0.911. After retaining 22 items, the Cronbach's coefficients of the six dimensions ranged from 0.708 to 0.870. (5) The test-retest reliability of the total scale, six dimensions, and 22 items were 0.936, 0.786-0.846, and 0.720-0.886, respectively. (6) The receiver operating characteristic curve of the scale was drawn with EPDS≥13 as the cut-off value, and the area under the curve (AUC) of EPDS was 0.808 (95% CI: 0.744-0.872). When the original cut-off point was 21, the Youden index was the max (0.561), with sensitivity and specificity of 0.952 and 0.609, respectively. The Kappa value was 0.691, indicating that the scale was consistent with EPDS. Conclusion:This study preliminarily established a Chinese urban version of the perinatal depression screening scale with a stable factor structure and good reliability and validity.
6.Development and reliability-validity testing of Chinese urban version of perinatal depression screening scale
Shan ZHANG ; Xueyun GAO ; Meina XU ; Jing LI ; Chengyin DOU ; Qinghong LI ; Dan ZHANG ; Rufang CHEN ; Shan WANG ; Yang MI ; Zhongliang ZHU ; Hui LI
Chinese Journal of Perinatal Medicine 2024;27(12):1042-1048
Objective:To develop a perinatal depression screening scale for Chinese urban version and test its reliability and validity.Methods:Naturally conceived women who were≥12 weeks of gestation and had regular prenatal examinations or delivered within four weeks in Xi'an and Foshan were recruited using convenience sampling. Initial entries were created through clinical interviews and expert validation of 50 of these pregnancies. Further item screening and testing for reliability and validity using correlation analysis, critical ratio method, homogeneity test, and factor analysis were performed. The final questionnaire was formed and then used to test the subjects. Fifty women who had completed the questionnaire effectively were selected for retesting 10 to 15 days after the initial evaluation. A structural equation model was constructed using the Edinburgh Postpartum Depression Scale (EPDS) as the reference criterion to conduct the scale's exploratory and confirmatory factor analysis. The receiver operating characters curve was used to determine the cut-off point of the scale.Results:(1) 1 300 questionnaires were issued, and 1 049 valid questionnaires were received with a recovery rate of 80.7%. Among them, 601 were used for exploratory and correlation analysis, and 448 were used for confirmatory factor analysis. (2) The initial entries of the scale totaled 63. After eliminating indicators that did not meet the requirements for item analysis, the final scale consisted of 22 entries in total. The final scale consisted of six dimensions, including "abnormal mood", "loss of interest and pleasure," "sleep disorder," "self-blame and guilt," "decline in conscious thought ability," and "lack of energy". (3) The correlation coefficients between the above six dimensions and EPDS were 0.609, 0.322, 0.423, 0.522, 0.545, and 0.516, respectively. The one between the total scale and EPDS was 0.715 (all P<0.01). (4) The confirmatory factor analysis of each model and the scale showed an acceptable fit and a stable factor structure with indices Chi-square/degrees of freedom =2.504, square root of approximation error=0.058, standardized root mean square residual=0.048, comparative fit index=0.925, Tueker-Lewis index=0.911. After retaining 22 items, the Cronbach's coefficients of the six dimensions ranged from 0.708 to 0.870. (5) The test-retest reliability of the total scale, six dimensions, and 22 items were 0.936, 0.786-0.846, and 0.720-0.886, respectively. (6) The receiver operating characteristic curve of the scale was drawn with EPDS≥13 as the cut-off value, and the area under the curve (AUC) of EPDS was 0.808 (95% CI: 0.744-0.872). When the original cut-off point was 21, the Youden index was the max (0.561), with sensitivity and specificity of 0.952 and 0.609, respectively. The Kappa value was 0.691, indicating that the scale was consistent with EPDS. Conclusion:This study preliminarily established a Chinese urban version of the perinatal depression screening scale with a stable factor structure and good reliability and validity.
7.Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice.
Shan LIN ; Meng-Yue ZHU ; Meng-Yu TANG ; Mi WANG ; Xiao-Dan YU ; Yi ZHU ; Shi-Ze XIE ; Dan YANG ; Jiadong CHEN ; Xiao-Ming LI
Neuroscience Bulletin 2023;39(2):245-260
Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.
Mice
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Animals
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Zona Incerta/metabolism*
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Neurons/metabolism*
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Fear/physiology*
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Somatostatin/metabolism*
8.Systematic Review of Methodological Guidelines for Health Technology Assessment at Home and Abroad
Peipei XU ; Wenrui LI ; Linan ZENG ; Dan LIU ; Yang ZHANG ; Xue MI ; Zongyao HUANG ; Haoxin SONG ; Lingli ZHANG
China Pharmacy 2020;31(12):1500-1499
OBJECTIVE:To evaluate guidelines f or health technology assessment (HTA)at home and abroad ,and to provide reference for scientific formulation of HTA guidelines in China. METHODS :Databases including PubMed ,Embase,Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ,including basic characteristics, content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS:A total of 19 guidelines published during 2001 to 2018 were included ,7 guidelines(36.8%)were published in 2015-2020;in addition to 1 guideline from WHO ,14 guidelines (73.7%)were published in Europeand ,2 guidelines(10.5%) in North America and 1 guideline each from South America and Asia (5.3%). There were 11 guidelines(57.9%)developed by academic organizations and 8 guidelines(42.1%)by health administration ;11 guidelines(57.9%)were evidence-based ,while the others weren ’t evidence- based (42.1%). The purpose ,content and object of assessment are demonstrated in 19 guidelines;18 guidelines specified the assessment method (94.7%),and 16 guidelines(84.2%)defined the subject of assessment ;14 guidelines (73.7%)specified the HTA assessment process ;12 guidelines(63.3%)mentioned the conflict of interest in HTA assessment process;7 guidelines(36.8%)mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ,but the core contents ar e basically the same. At present ,there is a lack of HTA guidelines in China. We can refer to foreign guidelines,and establish applicable HTA guidelines which aresuitable for national conditions ,so as to provide scientific guidance for HTA research.
9.Explore the Optimal Resolvent of Medical Needs and Mental Health for Patients with Lung Cancer during Epidemic Novel Coronavirus Pneumonia.
Haiyan XU ; Ke YANG ; Guangjian YANG ; Lu YANG ; Yuling MI ; Xiaohong CUI ; Min YANG ; Dan WANG ; Yan WANG
Chinese Journal of Lung Cancer 2020;23(4):247-254
BACKGROUND:
With the rapid spread of novel coronavirus pneumonia (NCP) worldwide and the escalation of prevention and control efforts, the routine medical needs of patients have been restricted. The aims were to investigate medical needs of lung cancer patients and their mental health status during the epidemic periods, so as to provide rational recommendations for subsequent diagnosis and treatment.
METHODS:
The questionnaire was sent in the form of an electronic questionnaire at 7am on 4th, March, 2020, until 7am 6th, March, 2020, 368 questionnaires were recollected from 25 provinces (autonomous regions/municipalities) in 48 h.
RESULTS:
Of the 368 patients, 18 patients were excluded as they didn't receive anti-tumor treatment, and 350 patients were included in the final analysis. 229 cases were treated with oral targeted drugs, and 121 cases were treated with chemotherapy or immunotherapy. 41.3% of patients treated with intravenous chemotherapy or immunotherapy experienced treatment discontinuation, and the proportion of treatment discontinuation in chemotherapy or immunotherapy was higher than those treated with oral targeted drugs (21.0%). Whether oral targeted drugs or intravenous chemotherapy or immunotherapy, more than 60% of patients experienced delays in imaging examinations. Nearly one third of patients developed new symptoms or exacerbation of existing symptoms. 26.6%-28.9% of patients have changed their treatment plans through online consultation. During novel coronavirus pneumonia, 40%-75% of lung cancer patients have mental health problems, and more than 95% of patients support government's prevention and control measures.
CONCLUSIONS
During the emergence of NCP, the medical needs of patients with lung cancer have not been enough, especially those who discontinued chemotherapy or immunotherapy. When medical institution resumes work, priority should be given to them. At the same time, mental health problems of patients should be valued and resolved timely.
Adult
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Aged
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Antineoplastic Agents
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therapeutic use
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Betacoronavirus
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physiology
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China
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epidemiology
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Coronavirus Infections
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epidemiology
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virology
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Female
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Humans
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Lung Neoplasms
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drug therapy
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psychology
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Male
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Middle Aged
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Pandemics
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Pneumonia
;
epidemiology
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virology
;
Pneumonia, Viral
;
epidemiology
;
virology
;
Retrospective Studies
10.Effect of Siwu decoction on the radiation injury of Zebrafish blood system
Xun ZHANG ; Nan ZHANG ; Yanru GUO ; Qi LIU ; Xue ZHOU ; Yingying MI ; Kang YANG ; Dan ZHU
Chinese Journal of Radiological Medicine and Protection 2020;40(11):820-825
Objective:To observe the effect of Chinese herbal compound Siwu decoction (SW) on radiation injury of zebra fish blood system, and to clarify whether zebra fish is a suitable model for this study. Methods:Totally 72 of 4-month-old adult male zebra fish ( Danio Rerio) with body weight ranging from 0.14 to 0.20 g were used in all the experiments, where 36 zebra fish were taken to observe the hemodynamic changes after radiation, and the other 36 zebra fish were used to study the intervention effect of Siwu decoction on the blood injury after radiation. Zebra fish was irradiated with 20 Gy of 60Co gamma-rays at a dose rate of 97.33 cGy/min. For the hemodynamic study, the peripheral blood and whole kidney marrow cells (WKMCs)of irradiated zebra fish and non irradiated control were collected on days 7, 14 and 30 after irradiation, respectively, and the cell number was detected by flow cytometry. For the Siwu decoction treatment, 36 zebra fish were randomly divided into non-irradiation group, irradiation group, SW2 000 group ( Siwu decoction was diluted by 2 000-fold) and SW5 000 group ( Siwu decoction was diluted by 5 000-fold). Siwu decoction was given on the second day after irradiation. Then the peripheral blood and WKM cells of zebra fish were collected at 7 d after irradiation for further analysis. Results:After irradiation, the dynamic of blood development of zebra fish were obviously changed with the most blood cell ablation at 7 d post-irradiation. The total number of peripheral blood cells and WKM cells decreased by 26% and 52%( t=4.535, 28.987, P<0.05), the number of myeloid monocytes, lymphocytes, and red blood cells in the WKM decreased by 46%, 79% and 33%( t=18.457, 66.900, 9.872, P<0.05), and the number of precursor cells decreased by 49% ( P>0.05). The numbers of these blood cells were partly recovered at 14 d after irradiation and returned to the normal level at 30 d after irradiation. In comparison with irradiation alone group, the numbers of WKM cells, myeloid monocytes, progenitor cells, lymphocytes and red blood cells increased by 57%, 125%, 81% and 35%, respectively ( t=12.128, 21.594, 15.473, 4.594, P<0.05), and peripheral red cells did not increase significantly in the SW5 000 group after irradiation. However, SW2 000 had no significant influence on radiation injury of zebra fish blood cells ( P>0.05). Conclusions:Radiation injury of the blood system of zebra fish could be recovered at a month after irradiation, and this radiation damage could be partly intervened by Siwu decoction at a suitable concentration, which provides a reference for the study of blood system regulation of traditional Chinese medicine.

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