1.Analysis of the application characteristics of the acute liver injury animal model based on data mining
Yilong HU ; Yinan ZHAO ; Shuangli ZHANG ; Guangnan QIU ; Yifan FENG ; Mingsan MIAO ; Jinxin MIAO
Chinese Journal of Comparative Medicine 2024;34(2):89-100
Objective To investigate the modeling elements of various types of animal models for acute liver injury,and to provide references and suggestions to establish and evaluate animal models of acute liver injury(ALI).Methods The animal experimental literature of ALI from 2002 to 2022 was searched in the databases of the China Knowledge Network,WanFang,Chongqing Vip(VIP),Chinese Medical Journal Full Text Data(Yiigle),and PubMed.The animal species,positive control drugs,modeling method,modeling drugs,and drug administration of the animal models of ALI in the literature were summarized.The result were analyzed using Excel,SPSS Modeler 18.0,and Cytoscape 3.8.2.Results A total of 896 articles were included in the databases.The most used animal models for ALI were male KM mice.The modeling method were mainly chemical liver injury,alcoholic liver injury,drug-related liver injury,and immune liver injury.①The corresponding main modeling method were intraperitoneal injection of 10 mL/kg of 0.1%CC14 in vegetable oil at 24 h before experiments,②gavage of 12.0 mL/kg of 50.0%~56.0%ethanol at 16 h before experiments,③intraperitoneal injection of 300 mg/kg APAP at 24 h before experiments,④tail vein injection of 20 mg/kg Con A at 8 h before experiments.Evaluation of the models was based on liver pathological indexes as the gold standard combined with biochemical indexes of serum ALT,AST,and SOD and MDA contents and activities in liver tissue homogenate as direct indicators.Conclusions Because the causes of ALI vary in clinical practice,the preparation of animal models of ALI should be based on the specific study content and characteristics,and the corresponding modeling method should be selected.
2.Clinical Characteristics and Treatment Options of Peripheral Spondyloarthritis
Lulu ZENG ; Xiaojian JI ; Lidong HU ; Jiawen HU ; Yinan ZHANG ; Jiaxin ZHANG ; Xingkang LIU ; Shiwei YANG ; Feng HUANG
Medical Journal of Peking Union Medical College Hospital 2024;16(1):50-58
To compare the differences in clinical features and treatment choices between peripheral spondyloarthritis(pSpA) and axial spondyloarthritis(axSpA), and better understand the clinical characteristics and medication needs of pSpA. Our study is a retrospective cohort study. The patients who first visited the First Medical Center of Chinese PLA General Hospital between January 2016 and December 2022 and were diagnosed with axSpA or pSpA according to the classification criteria established by the Assessment of SpondyloArthritis International Society were selected as the study subjects. Demographic data, clinical characteristics, laboratory tests, and treatment information of these patients were obtained through the electronic medical records management system and the intelligent management system for spondyloarthritis. The research compared the distribution of swollen and tender joints between pSpA and axSpA patients, as well as that between pSpA1(excluding patients with psoriatic arthritis) and axSpA patients. Additionally, we analyzed differences in clinical features and treatment options among these groups. A total of 1639 patients were included in the study, of which 184 had pSpA(including 97 with psoriatic arthritis), and 1455 had axSpA. Compared to axSpA patients, pSpA patients had fewer male patients(62.5% pSpA patients tend to have a later onset of disease, a lower proportion of male and HLA-B27 positivity, more associated peripheral arthritis, dactylitis, psoriasis, and a more common family history of psoriasis. The disease burden in terms of treatment for pSpA is not lower than that for axSpA. Due to the presence of more peripheral symptoms, psoriasis, and higher levels of inflammation, they also require more medication.
3.Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions
DU YINAN ; LI ZHIWEI ; ZHAO YUKUI ; HAN JING ; HU WEIPING ; LIU ZHIQIANG
Journal of Zhejiang University. Science. B 2024;25(1):23-37
5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.
4.Overview of behavioral evaluation methods of Parkinson's disease in rat and mouse and analysis of the characteristics of common animal models
Yilong HU ; Yinan ZHAO ; Jinxin MIAO ; Mingsan MIAO
Acta Laboratorium Animalis Scientia Sinica 2024;32(7):942-954
Parkinson's disease is the second most common neurodegenerative disease in middle-aged and elderly people.It is characterized by a long disease course and complex treatment process,introducing great challenges to society.Behavioral changes in animal models of Parkinson's disease can intuitively reflect the modeling situation of experimental animals and the effects of drug interventions.Therefore,selecting standardized animal models and appropriate behavioral assays is fundamental for both understanding the mechanisms of Parkinson's disease and developing anti-Parkinson drugs.In this paper,we summarize the method of behavioral experiments of Parkinson's disease using mice and rats at home and abroad and systematically summarize the experimental equipment,experimental method,evaluation indexes,and precautions of commonly used Parkinson's behavioral experiments.We also provide an overview of the commonly used animal models of Parkinson's disease and analyze their modeling mechanisms,alignment with the clinical features of Parkinson's disease,and respective advantages and disadvantages.This analysis will help researchers in choosing appropriate animal models of Parkinson's disease and behavioral testing method according to the purpose of the study.
5.Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes.
Xueying CHEN ; Xiaoyan YANG ; Yanhong REN ; Bingbing XIE ; Sheng XIE ; Ling ZHAO ; Shiyao WANG ; Jing GENG ; Dingyuan JIANG ; Sa LUO ; Jiarui HE ; Shi SHU ; Yinan HU ; Lili ZHU ; Zhen LI ; Xinran ZHANG ; Min LIU ; Huaping DAI
Chinese Medical Journal 2023;136(23):2839-2846
BACKGROUND:
The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.
METHODS:
In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.
RESULTS:
A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.
CONCLUSIONS
Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans
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Bronchoalveolar Lavage Fluid
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Prospective Studies
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Alveolitis, Extrinsic Allergic/diagnosis*
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Fibrosis
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Carbohydrates
6.Perioperative effects of da Vinci robot with totally no tube versus subxiphoid video-assisted thymectomy surgery for thymic tumors: A retrospective cohort study
Renquan DING ; Ming CHENG ; Shiguang XU ; Yinan ZHANG ; Wei XU ; Bo LIU ; Yuhang HU ; Xidong JIN ; Xilong WANG ; Shumin WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(06):818-823
Objective To compare the clinical efficacy and safety of da Vinci robot with totally no tube (TNT) versus subxiphoid video-assisted thymectomy surgery (SVATS) in the treatment of thymic tumors. Methods From 2019 to 2021, a retrospective analysis was conducted on patients with thymic tumor resection in the Department of Thoracic Surgery, General Hospital of Northern Theater Command. All patients underwent total thymectomy and mediastinal fat removal, and they were divided into a TNT group and a SVATS group according to the operation method. The intraoperative blood loss, conversion rate, postoperative visual analogue score (VAS), postoperative hospital stay time and postoperative complications were compared between the two groups. Results We finally included 435 patiets. There were 168 patients with 83 males and 85 females at an average age of 61.920±9.210 years in the TNT group and 267 patients with 147 males and 120 females at an average age of 61.460±8.119 years in the SVATS group. There was no death or postoperative myasthenic crisis in both groups. There was no statistical difference in postoperative hospital stay (1.540±0.500 d vs. 3.400±0.561 d, P=0.000), intraoperative blood loss (13.450±5.498 mL vs. 108.610±54.462 mL, P=0.000), postoperative 24 h VAS score (4.960±1.757 points vs. 3.600±1.708 points, P=0.000), or postoperative complication rate (3.0% vs. 11.6%, P=0.001). Conclusion TNT is a more efficient, safe, and effective surgical approach for treating thymic tumors, which can shorten hospital stay time and reduce postoperative complications. However, SVATS can minimize postoperative pain.
7.Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix.
Yue LIU ; Yating YANG ; Hanghang WANG ; Han LI ; Qi LV ; Xiachang WANG ; Dalei WU ; Lihong HU ; Yinan ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2023;21(8):599-609
Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.
Animals
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Mice
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Gynostemma
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Liver Cirrhosis/drug therapy*
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Triterpenes/pharmacology*
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Ginsenosides
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Extracellular Matrix
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Dammaranes
8.Herbal Textual Reseach on Haliotidis Concha in Famous Classical Formulas
Yixue ZHUANG ; Yinan LU ; Jingwen HU ; Yiqin ZHANG ; Jing MENG ; Zhilai ZHAN ; Chengzi YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):25-33
By reviewing the ancient materia medica, medical books and modern literature, this paper made a systematic textual research on Haliotidis Concha in famous classical formulas, including the name, origin, producing area, quality evaluation, harvesting and processing, in order to provide a basis for the development of famous classical formulas containing Haliotidis Concha. The textual research showed that Shijueming was the official name of Haliotidis Concha in past dynasties, and there were also aliases such as Qianliguang, Jiukongluo and Zhenzhumu named after its efficacy, properties and near-phonetic characters. Before the Tang dynasty, the original description of Haliotidis Concha was too concise, which could only be identified as the animal of genus Haliotis, family Haliotidae. During the Song, Yuan, Ming and Qing dynasties, the main varieties were H. diversicolor and H. discus hannai. At the beginning of the Republic of China, a variety of animals from genus Haliotis were used as Haliotidis Concha, and varieties were numerous and continued to this day. In ancient and modern times, the main producing areas in China are Hainan, Guangdong and Shandong, while the foreign producing areas are mainly Japan and Vietnam. The quality evaluation of Haliotidis Concha in ancient books was roughly determined by the number of openings of the expiratory orifice, and seven-hole and nine-hole abalone shells were preferred. In modern times, characters as big, neat, unbroken, clean inside and outside, lustrous, thick shells are preferred. Based on the textual research results and combined with the record years of the Shijueming San, it is suggested that the shells of H. diversicolor or H. discus hannai should be used in the development of this formula, and the raw products should be used as medicine.
9.Mechanism of Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma medicinal pair in delaying heart aging based on animal experiments and computer verification
Yiqing LIU ; Yan LEI ; Xue WANG ; Yinan LIU ; Jing YANG ; Chengkui XIU ; Yanhong HU
International Journal of Traditional Chinese Medicine 2023;45(7):852-860
Objective:To explore the mechanism of Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma medicinal pair in delaying heart aging based on animal experiments, network pharmacology and molecular docking. Methods:Mice were divided into control group, aging group, metformin group and TCM group according to random number table method. All the groups were injected subcutaneously by D-galactose except the control group to build the subacute aging model. Two weeks later, the metformin group was given metformin suspension (150 mg/kg), the TCM group was given Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma lyophilized powder solution (650 mg/kg), and the control group and aging group were given an equivalent volume of ultrapure water by gastric gavage, once a day, six times a week, for 10 weeks. The level of heart TERT mRNA was detected by PCR; the expression of heart p53 was observed by immunohistochemical staining; the morphology of heart tissue was observed by HE staining. TCMSP and SwissTargetPrediciton databases were used to retrieve the active components and targets of Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma medicinal pair; TTD, OMIM, Gene, HAGR, DisGeNET and other data platforms were used to screen the targets of heart aging; after the drug and disease targets were intersected, the active components of them were collected; STRING database, Cytoscape 3.8.0 software, etc. were used to make PPI of the intersection targets, and screen out the key targets; FunRich was used to perform enrichment analysis of cellular components, molecular functions, biological processes, and biological signal pathways for key targets; Schr?dinger Maestro software was used to do the molecular docking of the screened active components and key targets, and docking results were visualized via PyMOL 2.1 software. Results:Experiment results showed that Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma could significantly ameliorate the damage of aging heart tissues, elevate TERT mRNA level, while significantly reducing the positive expression of p53. A total of 32 active components from the medicinal pair were screened, corresponding to 637 target genes. There were 263 targets for heart aging, and 67 intersection targets of drug active component targets and heart aging targets. 31 key targets were obtained after screening. Enrichment analysis showed that molecular functions were related to transcription factor activity and protein-tyrosine kinase activity. Biological processes involved signal transduction and cell communication. Signaling pathways mainly involved PDGFR-beta, PI3K-Akt, S1P1, Glypican, TRAIL, and Glypican 1. The molecular docking results showed that kaempferol, suchilactone, and ginsenoside Rg5_qt in the medicinal pair had a strong binding ability to p53. Conclusion:Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma may achieve the effect of delaying heart aging by inhibiting p53 expression, providing a foundation for further research on mechanism of invigorating qi and activating blood circulation drugs to delay heart aging.
10.Prognostic prediction of the femoral head using osteonecrosis and contralateral regions based on CT images
Wenzhe ZHAO ; Shouye HU ; Yitong ZHAO ; Yinan LIU ; Yao LI ; Daning LI ; Dingxing HUANG ; Jian SUN
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(5):732-736
【Objective】 To develop a prognosis model based on CT images using radiomics method for patients with osteonecrosis of the femoral head (ONFH) and to investigate the additional prediction value of the imaging features of the contralateral normal femoral head regions for the prognosis prediction. 【Methods】 A total of 51 patients were included in this retrospective study. All the patients had preoperative CT images. For each patient, two regions of interest (ROIs) were involved, including the osteonecrosis region and the contralateral normal femoral head region. A total of 968 radiomics features were extracted for each patient. We made both the univariate and multivariable analyses. Three models were developed based on the features of osteonecrosis region, contralateral normal femoral head region, and both regions. The 10 times of repeated random experiments were used for model construction and validation. The average performance of the 10 times of experiments was reported as the results. 【Results】 For the features of osteonecrosis region, 37 features showed significant predictive value, with the mean AUC value of 0.708 2±0.029 9. The AUC of the constructed prediction model was 0.911 0±0.029 4 and 0.688 6±0.089 3 for the training set and validation set, respectively. For the features of contralateral normal femoral head region, 14 features showed significant predictive value, with the mean AUC value of 0.703 6±0.006 9. The AUC value of the constructed model for the training set and validation set was 0.867 2±0.039 5 and 0.669 0±0.072 6, respectively. For the models developed based on combined features, the AUC value was higher than that of the models developed based on osteonecrosis region features (training set: 0.935 8±0.016 6 vs. validation set: 0.737 9±0.090 8). 【Conclusion】 We developed a novel CT images-based radiomics method to predict postoperative prognosis in patients with ONFH. Furthermore, the features of contralateral normal femoral head region has additional prediction value. Combining the imaging features of osteonecrosis region and contralateral normal femoral head region can obtain more accurate prediction of prognosis in patients with ONFH.

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