1.Exploring on Mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos in Treatment of Acute Lung Injury Based on Serum Metabolomics
Wanshun CHANG ; Kang LI ; Zhaohua CHEN ; Yuqing HAN ; Yanwen CHEN ; Yanhui ZHU ; Zhenyu CHENG ; Haiying HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):117-125
ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos(FF) in the treatment of acute lung injury(ALI) by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week, and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide(LPS) solution by tracheal drip to establish an ALI model. After successful model establishment, the rats were randomly divided into the model group, the FF low-dose group(3.0 g·kg-1), the FF high-dose group(6.0 g·kg-1), and the dexamethasone group(5 mg·kg-1), with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution, and the blank group and the model group were gavaged with an equal amount of saline, treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin(HE) staining, wet/dry mass ratio(W/D) of the lung tissues, and protein concentration in rat bronchoalveolar lavage fluid(BALF). Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), combined with multivariate statistical analysis, the potential biomarkers of FF in treating ALI were screened by variable importance in the projection(VIP) value>1, P<0.05 from t-test, and log2fold change(FC)>1 or log2FC<-1. Kyoto Encyclopedia of Genes and Genomes(KEGG) database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate(S1P), phosphatidylinositol 3-kinase(PI3K), protein kinase B1(Akt1), and phosphorylated Akt1(p-Akt1) were examined by Western bolt. The expression levels of interleukin(IL)-6, IL-1β, and tumor necrosis factor(TNF)-α in BALF were detected by enzyme-linked immunosorbent assay(ELISA). ResultsCompared with the blank group, rats in the model group showed ALI pathological features such as alveolar lumen dilatation, interstitial hemorrhage and massive inflammatory cell infiltration, and the protein concentration in BALF and W/D of the lung tissues were significantly elevated(P<0.01). Compared with the model group, the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats, and the protein concentration in BALF and W/D were significantly decreased(P<0.05), and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways, including arginine biosynthesis, sphingomyelin metabolism, alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, α-linolenic acid metabolism, niacin and nicotinamide metabolism, and retinol metabolism. The results of Western bolt and ELISA showed that, compared with the blank group, the model group exhibited significantly elevated expression levels of S1P, PI3K, Akt1 and p-Akt1 proteins in the lung tissues, as well as increased expression levels of IL-6, IL-1β and TNF-α in BALF(P<0.01). Compared with the model group, the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group(P<0.05, P<0.01). ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism, and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.
2.Investigation of Mechanism of Qingqiao and Laoqiao on Acute Lung Injury Rats Based on Serum Metabolomics
Kang LI ; Tiantian LYU ; Rongqia CUI ; Shumin XIE ; Shujie GUO ; Wanshun CHANG ; Zhaohua CHEN ; Yanhui ZHU ; Mingsan MIAO ; Haiying HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):89-97
ObjectiveSerum metabolomics of acute lung injury(ALI) in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) to explore the similarities and differences in the mechanism of Qingqiao(harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color) and Laoqiao(harvested when the fruits of Forsythiae Fructus were ripe) in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week, 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide(LPS). After successfully constructing the ALI model, these rats was randomly divided into model group, Qingqiao group and Laoqiao group, with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg-1, while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin(HE) staining, wet-to-dry mass ratio(W/D) of lung tissues, and protein concentration in rat bronchoalveolar lavage fluid(BALF). The levels of interleukin(IL)-6, IL-1β and tumor necrosis factor(TNF)-α in BALF were quantified using enzyme-linked immunosorbent assay(ELISA). UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao, and serum metabolomics of rats in each group was analyzed, combined with multivariate statistical analysis with variable importance in the projection(VIP) value>1, P<0.05 from t-test, and fold change(FC)≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group, rats in the model group exhibited enlarged alveolar lumen, ruptured alveoli, interstitial hemorrhage, bronchial exudation of a large number of neutrophils and erythrocytes, and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues(P<0.01). In contrast, compared with the model group, rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs, and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased(P<0.01), the lung injury was significantly alleviated, but more obvious in the Qingqiao group. Compared with the blank group, the expression levels of IL-6, IL-1β and TNF-α in the BALF of the model group were significantly higher(P<0.01). Additionally, compared with the model group, the expression levels of IL-6, IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower(P<0.01). The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao, with 47 common components, 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats, 19 and 12 metabolites were called back by Qingqiao and Laoqiao, respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways, including linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, phenylalanine metabolism, ascorbate and aldarate metabolism, and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI, and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism, but the metabolic pathways affected by them are different.
3.The effect of radiofrequency heating on the expression of interleukin-1 beta and tumor necrosis factor alpha in osteoarthritic synovial membranes of the knee
Zhaohua FU ; Fei ZHANG ; Xianfeng WANG ; Yangmei SUN ; Qin DING ; Chang LIU ; Dong ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2021;43(9):776-780
Objective:To explore the effect of radiofrequency heating on the morphology of articular cartilage in the knee and the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the synovium using a rabbit model of knee osteoarthritis (OA).Methods:Fifty-four male rabbits had OA induced in their right hind limbs using the modified Hulth method. They were then randomly divided into a model group, a cervus and cucumis polypeptide (CCP) group and a radiofrequency thermotherapy (RT) group, each of 18. The CCP group was injected with deer melon peptide intramuscularly every day, while the RT group was given daily radiofrequency hyperthermia treatment at 36.5-38.5 ℃. The model group was not provided with any special treatment. On the 6th, 12th and 18th day of the treatment, 6 rabbits in each group were sacrificed to resect the right femur′s medial condyle cartilage. The morphological characteristics of the cartilage were evaluated using modified Mankins scoring, while the contents of lL-1B and TNF-a in the synovial membrane were detected using enzyme-linked immuno-sorbent assays.Results:The average Mankins scores and the levels of IL-1β and TNF-α decreased significantly at each time point, and significant differences were observed among the three groups. In the RT group the average Mankins score as well as the IL-1β and TNF-α levels decreased significantly with time throughout the experiment.Conclusions:Radiofrequency hyperthermia is superior to the injection of deer melon polypeptide in knee osteoarthritis, at least in rabbits. The therapeutic mechanism may be related to the control of IL-1β and TNF- α levels in the synovial membrane.
4.Advances in research on testis toxicity produced by cyclosporine A
Xiaoyan PAN ; Chang SUN ; Xue ZHANG ; Xuanxuan LIANG ; Xiyan WANG ; Zhaohua DOU ; Zhixin LI
Military Medical Sciences 2015;(8):641-643
Cyclosporine A( CsA) , as an immune inhibitor, is commonly used after organ transplantation.It has been found that the long-term use of CsA produced serious testicular toxicity and affected the fertility of organ transplantation patients.In order to investigate male reproductive damage induced by CsA, this article reviews its impact on reproductive organ development, its damage mechanism on the male reproductive system and drug research for alleviating its reproductive toxicity.It helps to make medical workers pay more attention to reproductive toxicity produced by CsA and make their efforts to develop some special drugs to lessen CsA reproductive toxicity.
5.Investigations on registration for three-dimensional mapping of cardiac chambers and computed tomography segmented images.
Jingjing GONG ; Yiyong SUN ; Zhaohua CHANG
Journal of Biomedical Engineering 2011;28(3):573-578
In this paper, a novel registration method is presented for three-dimensional mapping of cardiac chambers and computed tomography (CT) segmented surfaces. The proposed method applies random perturbations to three-dimensional mapping of cardiac chambers in order to move out of local minima. It effectively solves the problem of the existing algorithm based on iterative closest point (ICP) in which the optimization often falls into local minima, and improves the registration accuracy and success rate. The registration experiment results show that the final registration accuracy and success rate of the proposed method are better than the existing ICP-based algorithm, and it can implement the registration when the three-dimensional mapping of cardiac chambers and CT segmented surface have a wide range of initial offset.
Algorithms
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Heart
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diagnostic imaging
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Humans
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Image Processing, Computer-Assisted
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methods
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Imaging, Three-Dimensional
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Pattern Recognition, Automated
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methods
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Tomography, X-Ray Computed
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methods
6.The current situation of the development of cryoablation apparatus
Qingxiao ZHAO ; Zhaohua CHANG ; Lei LI
Journal of Interventional Radiology 2006;0(07):-
This article aims to introduce the progress, mechanism, advantage, disadvantage and application of cryoablation technique, as well as the most advanced instruments in the world nowadays, which have been clinically used for the treatment of cancer, and their operating principles and functions.The following are some of the state-of-the-art cryoablation instruments:the ArcticFront balloon catheter for the ablation of pulmonary vein(CryoCath Technologies Inc., Canada), the V-probe(Endocare Inc., U.S.A.), which can generate iceball of five different diameters by adjusting the slip-twisting position, the 1.47 mm diameter probe(Galil-medical Inc., Israel), the Cryo-s(Metrum-cryoflex Inc., Denmark), and cryosurgery-hyperthermia equipment and"nano frozen"technique(Liu Jing's Study Group).The prospect of cryoablation technique is also discussed in this paper.

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