1.Role of Naoan capsules in treatment of ischemic stroke by network pharmacology combined with GEO database and molecular docking
Shu-Xian YANG ; A-Ning SUN ; Bin ZHU ; Wei-Zhong SHI ; Zhi-Gang ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(3):435-439
Objective To predict and verify the mechanism of Naoan capsules(NAC)in treatment of ischemic stroke(IS)by network pharmacology,Gene Expression Omnibus(GEO)database,and molecular docking technology.Methods The active components in NAC were collected using the Traditional Chinese Medicine System Pharmacological Analysis Platform,and the disease-related differential genes were screened using GEO database.After screening and obtaining the common targets of the two,the compound disease network was constructed by Cytoscape 3.8.2 software.At the same time,protein-protein interaction networks were created to identify candidate targets for NAC treatment of IS,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed.Finally,core targets were verified by molecular docking technology.Results A total of 56 candidate compounds and 18 544 disease-related differential genes were screened.Further,quercetin,kaempferol,luteolin and baicalein were found to be the key active compounds of NAC in the treatment of IS through the compound disease network.In the search of PPI network core,eight key targets for NAC treatment of IS were screened,including mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma factor 2(Bcl-2),cysteinylaspartate specific protease 3(CASP3),etc.In addition,the key pathways of NAC treatment of IS are mainly concentrated in lipid and atherosclerosis,advanced glycation end products and receptor for advanced glycation end products(AGE-RAGE),tumor necrosis factor(TNF),interleukin17(IL-17),C-type lectin receptor,apoptosis,hypoxia-inducing factor-1(HIF-1),MAPK and other signaling pathways.Finally,the molecular docking results showed that the key active compounds(quercetin,kaempferol,luteolin and baicalein)had good binding force with the 8 key targets,which initially verified the results of network pharmacology.Conclusion NAC plays a role in the treatment of IS through multi-component,multi-target and multi-pathway.
2.Analyzing the impact of electroacupuncture on the structure and function of gut microbiota by using microbiota-derived extracellular vesicles in high-fat diet-induced obesity mice
Xian-Yun WANG ; Yuan-Cheng SI ; Lu-Qi GAO ; Zhi-Ju LI ; Zhao-Xia KANG
Parenteral & Enteral Nutrition 2024;31(2):65-72
Objective:To explore the effects of electroacupuncture in regulating the intestinal flora of high-fat diet (HFD)-fed mice from microbiota-derived extracellular vesicles. Methods:Obese mice with established nutritional obesity model were randomly divided into either the model group (n=10) or the electroacupuncture group (n=10). Acupuncture groups were chosen to pinprick points of Zhongwan, Guanyuan, Tianshu and Zusanli. Stool samples were collected from groups at the end of the intervention and extracellular vesicles (EVs) were isolated using ultracentrifugation. The morphology of EVs isolated from the stool was confirmed by transmission electron microscopy (TEM) and analysis of the associated intestinal flora by extracting microbial DNA from them for 16S rRNA sequencing. Results:The weight and Lee's index of obese mice decreased significantly after electroacupuncture intervention treatment (P<0.01). TEM images showed that EV extracted from stools were in the form of round or oval double-membraned vesicle-like structures. The 16S rRNA sequencing analysis showed that at the phylum level, the relative abundance of Proteobacteria in the model group was significantly higher than that of the normal group (P<0.05), while the relative abundance of Frimicutes and Bacteroidetes was significantly lower than that of the normal group(P<0.05). At the genus level, expressions of Psychrobacter and Planomicrobium in the model group were significantly higher than those in the normal group (P<0.01), while expressions of Solibacillus, Solibacillus, Proteus, Lactobacillus, Agrobacterium, Enterobacter, Brevundimonas, and Comamonas were significantly lower than those in the normal group (P<0.05). After electroacupuncture intervention, the intestinal microbial diversity of experimental mice increased, and the flora structure was closer to that of normal mice. Conclusion:Structural changes in the gut flora of nutritionally obese mice accompanied by changes in gut microbial-derived EVs profiles, and 16S rRNA sequencing analysis showed that microbial DNA in gut microbial-derived EVs reflected the composition of the gut microbiota, and that electroacupuncture for the treatment of obesity was not only related to the modulation of the gut flora, but was also closely related to gut microbial-derived EVs.
3.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
4.Effect of L-Type Amino Acid Transporter 1 Expression on Clinicopathological Features and Prognosis of Non-Hodgkin's Lymphoma
Zhi-Fang ZHAO ; Xiu-Jun HAO ; Yan-Min YANG ; Wei-Ge XU ; Yun-Xiao ZHANG ; Xian-Hua YUAN
Journal of Experimental Hematology 2024;32(2):434-438
Objective:To detect the expression of L-type amino acid transporter 1(LAT1)in non-Hodgkin's lymphoma(NHL)tissues,and analyze its effect on clinicopathological characteristics and prognosis of patients.Methods:A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected.The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features(including sex,Ann Arbor stage,extranodal infiltration,Ki-67).The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression.Receiver operating characteristic(ROC)curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality,and analyzing the effect of percentage of LAT1-positive cells on survival rate.Results:LAT1 was positively expressed in NHL tissue.The high expression rate of LAT1 in Ann Arbor stage Ⅲ and Ⅳ groups were higher than that in Ann Arbor stage Ⅰ group,that in extranodal infiltration group was higher than non-extranodal infiltration group,and that in Ki-67 positive expression group was higher than Ki-67 negative expression group(all P<0.05).The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%,which was lower than 91.2%in low-LAT1 expression group(P<0.05).Ann Arbor stage Ⅲ and Ⅳ,extranodal invasion,Ki-67 positive expression and increased expression of LAT1(LAT1-positive cell percentage score ≥ 2)were risk factors for mortality.The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%,and the area under the ROC curve was 0.905(95%CI:0.897-0.924).The 3-year survival rate of high-LAT1 level group(the percentage of LAT1-positive cells ≥ 45.6%)was 50.00%,which was lower than 78.26%of low-LAT1 level group(P<0.05).Conclusion:The expression level of LAT1 in NHL tissue increases,which affects Ann Arbor stage and extranodal infiltration of patients.LAT1 is a risk factor for death.
5.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.
6.Exploring mechanism of Banxia Baizhu Tianma Decoction in intervening methamphetamine addiction from PI3K-Akt pathway and cell verification based on network pharmacology and cell verification
Han-Cheng LI ; Zhao JIANG ; Yang-Kai WU ; Jie-Yu LI ; Yi-Ling CHEN ; Ming ZENG ; Zhi-Xian MO
Chinese Pharmacological Bulletin 2024;40(10):1971-1978
Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P<0.01)and low expression of 5-HT(P<0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P<0.05)and p-Akt/Akt(P<0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.
7.Investigation on the use and management of medical devices in different primary medical and health institutions under hierarchical medical diagnosis and treatment
Wei ZHAO ; Qiujun ZHANG ; Wenxiu LIU ; Zhi CHEN ; Bohan QU ; Xian LI
China Medical Equipment 2024;21(5):150-154,160
Objective:To investigate the current status of the use and management of medical devices in various primary medical and health institutions under hierarchical medical diagnosis and treatment.Methods:A stratified random cluster sampling method was used to select 450 medical personnel from 50 township and urban primary medical and health institutions of Shijiazhuang from May to August 2023 and a questionnaire network survey on the use and management of medical devices was conducted,which covered 16 items across three dimensions including the use of commonly used medical devices in primary medical institutions,maintenance and quality control management.Results:A total of 450 questionnaires were distributed and 450 valid questionnaires were collected,including 239 from township primary level medical institutions and 211 from urban primary level ones.According to the results of 211 urban primary level questionnaires,the proportions of the training and examination carried out by the medical staff of urban grass-roots medical and health institutions prior to the use of medical devices,understanding parameters of medical devices and timely detection of malfunction of medical devices were 62.6%(132/211),77.7%(164/211)and 70.1%(148/211),respectively,which were higher than those at the township primary level,the difference was statistically significant(x2=17.750,29.649,22.384,P<0.05).The proportions of urban primary medical and health institutions with maintenance system,inspection and maintenance standards,regular calibration provisions,and equipment calibration standards were 64.0%(135/211),53.6%(112/211),55.9%(118/211)and 55.0%(116/211),respectively,which were higher than those of the township primary level,the difference was statistically significant(x2=5.834,34.728,6.004,25.540,P<0.05).The difference was not statistically significant between urban primary level and township primary level in each item of quality control management(P>0.05).Conclusion:Primary medical and health institutions were required to strengthen training and assessment before medical and health personnel use medical devices;improve related system and standards for medical device maintenance;formulate quality control management system for commonly used medical devices;strengthen analysis and discussion processes after quality control,and promote continuous improvement of medical device quality management.
8.Comparison of growth and quality of wild and cultivated Artemisia stolonifera.
Shuang-Ge LI ; Ya-Chen ZHAO ; Hui LI ; Xian-Zhang HUANG ; Ting WU ; Hong-Zhi DU ; Da-Hui LIU
China Journal of Chinese Materia Medica 2023;48(14):3722-3729
This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.
Artemisia
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Agriculture
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Flavonoids
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Plant Leaves
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Drugs, Chinese Herbal
9.Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease.
Xi-Wei SHEN ; Zhi-Yuan TANG ; Xian-Juan SHEN ; Jian-Mei ZHAO
Chinese Journal of Contemporary Pediatrics 2023;25(6):579-586
OBJECTIVES:
To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments.
METHODS:
ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells.
RESULTS:
PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05).
CONCLUSIONS
PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.
Child
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Humans
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Animals
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Mice
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Mice, Inbred C57BL
;
Becaplermin
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Imatinib Mesylate/therapeutic use*
;
Mucocutaneous Lymph Node Syndrome/drug therapy*
;
Phosphatidylinositol 3-Kinases
;
Proto-Oncogene Proteins c-akt
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Thrombocytosis/etiology*
;
RNA, Messenger
10.Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption.
Qiong-Yu ZHANG ; Yan GUO ; Xiao-Liang JIANG ; Xing LIU ; Shu-Guang ZHAO ; Xian-Liang ZHOU ; Zhi-Wei YANG
Journal of Geriatric Cardiology 2023;20(7):538-547
OBJECTIVES:
To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH).
METHODS:
In the first part, 2-month-old CCKBRfl/fl villin-Cre mice (CKO) and control CCKBRfl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo.
RESULTS:
The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice, but no significant histopathological changes were observed.
CONCLUSIONS
These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBRfl/fl villin-Cre mice. The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

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