1.Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression, elucidating the curative mechanism of Danzhi Xiaoyao powder
Kunyu Li ; Leiming You ; Jianhua Zhen ; Guangrui Huang ; Ting Wang ; Yanan Cai ; Yunan Zhang ; Anlong Xu
Journal of Traditional Chinese Medical Sciences 2024;11(1):3-20
Objective:
To investigate the molecular mechanism and identify potential drugs for subthreshold depression (SD), and elucidate the detalied mechanism of Danzhi Xiaoyao powder (DZXY) in SD.
Methods:
Using RNA-sequencing, we identified differentially expressed genes (DEGs) in leukocytes of SD compared to healthy controls, deciphered their functions and pathways, and identified the hub genes of SD. We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELiS platform. The Connectivity Map database was retrieved to screen candidate drugs for SD. Based on network pharmacology, we elucidated the “multi-component, multi-target, and multi-pathway” mechanism of DZXY in the treatment of SD.
Results:
We identified 1080 DEGs (padj <0.05 and |log2 (fold change)| ≥ 1 & protein coding) in the leukocytes of patients with SD. These DEGs, including hub genes, were primarily involved in immune and inflammatory response-related processes. Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells. Connectivity Map analysis identified 28 potential drugs for SD treatment, particularly SB-202190 and TWS-119. Constructing the “Direct Compounds-Direct Targets-Pathways” network for DZXY and SD revealed the curative mechanisms of DZXY in SD, primarily including inflammatory response, lipid metabolism, immune response, and other processes.
Conclusion
These results provide new insights into the characteristics and functional changes of leukocytes in SD, partially illustrate the pathogenesis of SD, and suggest potential drugs for SD. The curative mechanisms of DZXY in SD are also partially elucidated.
2.Comparison on radiation doses of in vitro pre-fenestration and in situ fenestration thoracic endovascular aortic repair in treatment of aortic disease
Fang XUE ; Xiaofeng HAN ; Gang WANG ; Lei SHAO ; Guangrui LIU ; Tiezheng LI ; Xi GUO ; Wei QIU ; Xiaohai MA
Chinese Journal of Interventional Imaging and Therapy 2024;21(9):553-556
Objective To compare the radiation dose of in vitro pre-fenestration and in situ fenestration thoracic endovascular aortic repair(TEVAR)in treatment of aortic disease.Methods Data of 51 patients with aortic diseases who received in vitro pre-fenestration(group A)and 21 cases who underwent in situ fenestration(group B)TEVAR were retrospectively analyzed.The fluoroscopy duration,total reference air kerma(AK),total dose area product(DAP)and TEVAR time were compared between groups.Results TEVAR was successfully completed in all 72 patients.Fluoroscopy duration([21.42±8.04]min vs.[34.57±9.07]min)and total DAP(44315.0[31157.0,56307.5]μGy·m2 vs.72153.0[45460.0,82354.0]μGy·m2)in group A were both significantly lower than those in group B(both P<0.05),while total AK(2423[1638,3533]mGy vs.3600[1898,3921]mGy)and TEVAR time([83.41±22.89]min vs.[81.00±22.13]min)in group A were not significant different from those in group B(both P>0.05).Conclusion Compared with in situ fenestration TEVAR,both the fluoroscopy time and total DAP of in vitro pre-fenestration TEVAR significantly reduced for treating aortic diseases.
3.Effects of radon exposure on lung function and metal balance in mice
Huimeng LIU ; Meiyu WANG ; Guangrui CHEN ; Huiyu ZHOU ; Yong YUAN ; Zhiyun MENG ; Ruolan GU ; Hui GAN ; Zhuona WU ; Guifang DOU
Chinese Journal of Radiological Medicine and Protection 2022;42(11):845-850
Objective:To explore the disturbance of metal element balance in mice after exposure to radon.Methods:Mice were randomly divided into control group, radon exposure of 30 WLM group, 60 WLM group and 120 WLM groups, with 10 mice in each group. After radon exposure with the cumulative dose, the lung function of mice was detected by a non-invasive pulmonary function testing instrument. Mice blood was taken from eyeballs. The lungs, heart, liver, kidney and spleen were also collected. HE staining was used to observe the pathological changes of lung tissue. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the content of metal elements, including essential trace elements in the body: chromium (Cr), molybdenum (Mo), cobalt (Co), selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), nickel (Ni), and potentially toxic elements: arsenic (As), tin (Sn), lead (Pb), aluminum (Al), mercury (Hg), cadmium (Cd), and silver (Ag).Results:Compared with the control group, lung ventilation function of the radon-exposed mice was decreased, alveolar structure was destroyed, and the contents of pulmonary metal elements Cr, Al, Pb, Sn( F=0.34, 0.66, 3.14, 1.16, P<0.05) and essential trace elements Mn, Cr, Zn, and Mo in the blood were decreased( F=0.65, 1.44, 0.97, 2.08, P<0.05), while the elements of Cu, Mo, Se and As in the lungs were increased( F=1.31, 1.26, 0.81, 2.04, P<0.05), and the element contents in other tissues also fluctuated. Conclusions:Inhalation of a certain cumulative dose of radon can reduce the lung ventilation function of mice and induce lung inflammation, as well reduce the content of essential trace elements in the lung and blood so that the content of metal elements in the body fluctuates.
4.Effect of Yinxing Mihuan Oral Solution on Neovascularization and Vascular Remodeling in Chemical Photothrombosis-induced Focal Cerebral Ischemia Mouse Model
Mingjiang YAO ; Wei ZHANG ; Bin YANG ; Wenting SONG ; Guangrui WANG ; Yimin WANG ; Yong WANG ; Shaoqing HE ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(23):38-43
ObjectiveTo investigate the effects and underlying mechanism of Yinxing Mihuan oral solution (YM) on neovascularization and vascular remodeling in chemical photothrombosis-induced focal cerebral ischemia model in mice. MethodFifty SPF C57BL/6J mice were randomly divided into sham group, model group, ginaton group (12.5 mg·kg-1), and low- (YM-L, 412 mg·kg-1) and high-dose (YM-H, 824 mg·kg-1) YM groups, with 10 mice in each group. The focal cerebral ischemia model was established by chemical photothrombosis method. Drugs in each group were administered by gavage for 14 consecutive days after operation. The modified neurological severity score (mNSS) and measurement of forelimb grasping were used to evaluate the neurologic impairment of mice. The vascular density of infarct border-zone (IBZ) was measured by fluorescein labelled dextran (FITC-dextran) method. The morphology of IBZ was evaluated and observed by hematoxylin-eosin (HE) staining. The expression of proteins related to neovascularization and vascular remodeling in brain tissues, including vascular endothelial growth factor (VEGF), platelet and endothelial cell adhesion molecule 1 (CD31), hypoxia-inducible factor-1α (HIF-1α), von Willebrand factor (vWF), and angiogenin (ANG), was detected by Western blot. ResultCompared with the sham group, the model group showed manifest neurological deficits (P<0.01), weakened forelimb grasping (P<0.01), increased vascular density of IBZ (P<0.01), and obvious pathological changes, such as neuronal necrosis and gliocyte proliferation. After treatment for 14 days, compared with the model group, the YM-H group showed improved neurological deficits (P<0.01), and the YM-L group and the YM-H group showed strengthened forelimb grasping (P<0.01). Moreover, the YM-L group displayed increased vascular density of IBZ (P<0.05), reduced pathological damage, and up-regulated protein expression of CD31, ANG, HIF-1α, and vWF (P<0.05, P<0.01). ConclusionYM could improve motor function and pathological morphological impairment in chemical photothrombosis-induced focal cerebral ischemia mouse model, and the underlying mechanism might be related to the promotion of neovascularization and vascular remodeling in IBZ.
5.Discrimination of TCM constitutions by biochemical and routine urine indexes
Liu XIAOLING ; Zhao PENGFEI ; Zhen JIANHUA ; Zhang SHEN ; Wang HESONG ; Sun YUXIU ; Wang WEI ; Wang TINGJIAN ; Hu KAIWEN ; Huang GUANGRUI
Journal of Traditional Chinese Medical Sciences 2022;9(2):153-159
Objective:To investigate whether the specific traditional Chinese medicine(TCM)constitution of in-dividuals can be defined by certain biological indexes instead of answering the questionnaire,and to explore the possibility of discriminating nine TCM constitutions from each other simultaneously using biological indexes.Methods:Blood and urine samples from 152 individuals with nine TCM constitutions were collected,and the related biological indexes were analyzed combining ANOVA,multiple comparison,discriminant analysis,and support vector machine.Results:We found that 4 out of 24 blood routine indexes,7 out of 10 urine routine indexes,and 12 out of 32 biochemical indexes showed differences among the constitutions.High-sensitivity C-reactive protein,apolipoprotein A1,and alkaline phosphatase were potential candidates for screening out individuals with unbalanced constitutions.Combining uric acid,high-density lipoprotein,apolipoprotein A1,creatine kinase,total protein,aspartate aminotransferase,total bile acid,dehydrogenase,sodium,and calcium levels had the potential to directly distinguish the nine TCM constitutions from each other.Among these indexes,the highest ratio of discriminant analysis between two constitutions was 95.5%,while the lowest was 66.1%.Conclusion:Our results suggest that some biochemical and urine indexes are related to various TCM constitutions,and thus they have the potential to be used for TCM constitution classification.
6.Effect of butylphthalide and sodium chloride injection combined with salvia miltiorrhiza injection in the treatment of acute ischemic stroke
Guangrui DENG ; Jiamin WU ; Zhijun WANG ; Chunwang LIU
Chinese Journal of Primary Medicine and Pharmacy 2018;25(16):2074-2077
Objective To investigate the value of butylphthalide and sodium chloride injectio combined with compound salvia miltiorrhiza injection in the treatment of acute ischemic stroke.Methods From January 2016 to December 2017,104 patients with acute ischemic stroke in Tongji Huangzhou Hospital Affiliated to Huazhong University of Science and Technology were randomly divided into observation group (52 cases) and control group (52 cases) according to the digital table.The control group was given butylphthalide and sodium chloride injectio,and the observation group was combined with the compound salvia miltiorrhiza injection on the basis of the control group.The courses of the treatment in the two groups were 14 d.The effects of the two groups were compared.Results The total effective rate of the observation group(90.38%,47/52) was higher than that of the control group(73.08%,38/52) (x2 =5.216,P < 0.05).After treatment,the daily living activity (ADL) score of the observation group was (60.49 ± 5.46) points,which was higher than (44.54 ± 4.10) points of the control group (t =16.845,P < 0.05).After treatment,endothelin-1 (ET-1),C reactive protein (CRP),homocysteine (Hcy) in the observation group were (37.42 ± 5.47) ng/L,(6.51 ± 1.89)mg/L,(7.42 ± 1.27) μmol/L,respectively,which in the control group were (58.98 ± 7.89) ng/L,(12.34 ± 2.65) mg/L,(15.39 ± 2.06) μmol/L,respectively,the levels of ET-1,CRP and Hcy in the observation group were lower than those in the control group (t =16.194,12.916,23.749,all P < 0.05).After treatment,the plasma viscosity,fibrinogen,whole blood viscosity at high shear and low shear whole blood viscosity of the observation group were (1.20 ± 0.23) mPa/s,(2.54 ± 0.37) g/L,(2.54 ± 0.37) mPa/s and (8.19 ± 0.68) mPa/s,respectively,which of the control group were (2.09 ± 0.32) mPa/s,(3.47 ± 0.58) g/L,(3.46 ± 0.59) mPa/s and (9.81 ± 0.82) mPa/s,respectively,the plasma viscosity,fibrinogen,whole blood viscosity at high shear and low shear whole blood viscosity of water of the observation group after treatment were lower than those of the control group(t =16.286,9.748,10.994,10.966,all P < 0.05).Conclusion The effect of butylphthalide and sodium chloride injectio combined with compound salvia miltiorrhiza injection in the treatment of acute ischemic stroke is significant,which is worth studying.
7.Study on Qi-supplementing and Mind-tranquilizing Efficacy ofLing-Qi-JiaOral Solution on Heart-spleen Deficiency Mouse
Li XU ; Wenting SONG ; Bing HAN ; Xiaodi FAN ; Jie HAN ; Guangrui WANG ; Jianxun LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1361-1366
This study was aimed to observe the body weight and behavioral changes of heart-spleen deficiency mouseandtoassesstheefficacyofLing-Qi-Jia (LQJ)oralsolutiononqi-supplementingandmind-tranquilizing. The heart-spleen deficiency syndrome mouse model was established by using loading swimming anddrugdaily.Thebodyweight,foodconsumption,intestinepropulsion,tailsuspensiontest (TST),forced swimmingtest (FST),sleepingtimeandtheamountofbrainneurotransmitterweredetected.Theresultsshowed that mouse suffered loading swimming and drug formed heart-spleen deficiency syndrome model, which were indicated by lowering body weight and food consumption, shortened time in FST, prolonged accumulative immobility time in TST, intestine propulsion hyperfunction, shortened sleeping time and lowering brain neurotransmitter amount. LQJ oral solution can obviously improve experiment indexes mentioned above. It was concluded that LQJ oral solution, which can improve insomnia due to heart-spleen deficiency, might had close relation to the efficacy of qi-supplementing and mind-tranquilizing. Meanwhile, changes of brain neurotransmitters might also be the material basis on its efficacy.
8.Effect ofRong-ShuanCapsule on Rodent Tolerance against Cerebral Ischemia, Hypoxia and Cerebral Reserve Capacity
Li XU ; Wenting SONG ; Jianxun REN ; Guangrui WANG ; Sheng ZHU ; Mingjiang YAO ; Jianxun LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1386-1391
This study was aimed to observe the effect ofRong-Shuan (RS) capsule on rodent tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity, which was related to promote blood circulation and remove blood stasis. Acute cerebral ischemia and anoxia models were established by permanent left carotid artery ligation on C57 BL/6 mice and hypoxia inhalation (O2?N2 = 8?92) for 15 min. Duodenal administration of RS capsule at different doses (100, 200 or 400 mg·kg-1) or saline were given 10 min after ischemia onset. The local brain blood circulation changes and neurobehavioral function were evaluated 24 h after ischemia onset. SD rats were given RS capsule at different doses (75, 150, 300 mg·kg-1) or saline. The effect of RS capsule on improvement of microcirculation disturbance induced by high molecular dextran was observed. The results showed that compared with the sham operation group, the brain blood circulation in the model group was significantly decreased; the cerebral infarction area increased; and the behavioral score after cerebral hypoxia was significantly increased (P < 0.05, orP < 0.01). Meanwhile, after the injection of high molecular dextran among rats in the model group, the cerebral leptomeninx microcirculation was obviously slowed down at 3 timepoints, which were 10, 20 and 30 min. Compared with the model group, RS capsule (400 mg·kg-1) can significantly increase the local blood circulation in the brain of mice, improve behavioral disturbance, reduce cerebral ischemia area (P< 0.05, orP < 0.01). RS capsule can also improve blood flow velocity and flow pattern in cerebral leptomeninx microcirculation disturbance induced by high molecular dextran at different timepoints (P < 0.05, orP < 0.01). It was concluded that RS capsule can increase the tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity in order to protect the neural tissues to promote neuronal recovery.
9.Study on Effect ofQi-supplementing and Depression-relieving ofJie-Du Tong-LuoCapsule on Post-stroke Depression Rat Model
Wenting SONG ; Li XU ; Jianxun REN ; Mingjiang YAO ; Guangrui WANG ; Jianxun LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1380-1385
This study was aimed to observe behavioral changes of post-stroke depression (PSD) rats, and to assess effect ofJie-Du Tong-Luo(JDTL) capsule onqi-supplementing and depression-relieving. Microspheres were injected from external carotid artery of rats under anesthesia to prepare the multiple cerebral infarction. Aftermid long term feeding, PSD rat model was established. Then, open-field test (OFT), tail suspension test (TST), forced swimming test (FST) and glucose preference test were employed to study behavioral changes of rats. The results showed that rats suffered multiple cerebral infarction after mid long term feeding formed PSD, which were indicated by reduced food consume, slow body weight increasing, reduction of spontaneous movement and inquiry activity, prolonged accumulative immobility time in TST, FST and lowered glucose preference, compared with rats in the normal group. Compared with the model group, rats in the JDTL capsule group andBu-Chang Xin-Nao-Tonggroup showed larger body weight increase, higher scores in OFT, reduced immobility time in TST, FST, and elevated glucose preference. It was concluded that JDTL capsule had significant efficacy on rats’ body weight, behavior and glucose preference, which might be its pharmacological basis onqi-supplementing and depression-relieving.
10.Value of fractional flow reserve measurement in endovascular therapy for patients with Stanford B type aortic dissection complicated with renal blood flow injury
Xi GUO ; Peng LI ; Guangrui LIU ; Xiaoyong HUANG ; Qiang YONG ; Guoqin WANG ; Lianjun HUANG
Chinese Journal of Cardiology 2015;43(10):854-857
Objective To analyze the value of fractional flow reserve (FFR) measurement on endovascular therapy for patients with renal artery stenosis.Methods Clinical data of 12 patients with Stanford B type aortic dissection complicated with renal blood flow injury in Anzhen hospital hospitalized from May 2013 to February 2014 were retrospectively analyzed.Renal artery angiography was performed and fractional flow reserve (FFR) was measured before Thoracic endovascular aortic repair.After operation, renal artery FFR was measured again, and renal artery stenting was performed in patients with FFR≤0.90 or average pressure difference between proximal and distal of renal artery > 20 mmHg(1 mmHg =0.133 kPa) and not applied for patients with FFR > 0.90.The patients were then subsequently followed up clinically.Kidney function were measured after 1 month, and contrast-enhanced ultrasonography data were obtained at 1 and 3 months later, respectively.Results The FFR of 1 patient was 0.90, while the FFR of other patients were less than 0.90 before thoracic endovascular aortic repair.After the procedure, the angiography showed that the blood flow of renal artery in 8 patients were fluency, and the FFR index was over 0.90.There were 4 patients with FFR less than 0.90.After renal artery stenting, the FFR of these 4 patients were all above 0.90.Compared with pre-procedure, blood urea nitrogen ((8.84 ± 3.99) mmol/L vs.(5.18 ± 1.69) mmol/L, P =0.011) and uric acid ((359.3 ± 77.3) μmol/L vs.(276.9 ± 108.3) μmol/L, P =0.008) decreased significantly after 1 month, and there was no significant difference in serum creatinine (P =0.760).Contrast-enhanced ultrasonography results showed that blood flow of renal artery were fluency after 1 month and 3 months.Conclusion In patients with aortic dissection complicating renal blood flow injury, the FFR measurement is meaningful in evaluating the blood flow status of target organs and guide the endovascular revascularization


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