1.Anti-osteoporotic mechanisms of kaempferol based on gut microbiota and comprehensive targeted metabolomics
Zhou LIANG ; Chi ZHANG ; Chengzhen PAN ; Bo YANG ; Zhanglin PU ; Hua LIU ; Jinhui PENG ; Lichun WEN ; Guanhan LING ; Feng CHEN
Chinese Journal of Tissue Engineering Research 2025;29(20):4190-4204
BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.
2.Anti-osteoporotic mechanisms of kaempferol based on gut microbiota and comprehensive targeted metabolomics
Zhou LIANG ; Chi ZHANG ; Chengzhen PAN ; Bo YANG ; Zhanglin PU ; Hua LIU ; Jinhui PENG ; Lichun WEN ; Guanhan LING ; Feng CHEN
Chinese Journal of Tissue Engineering Research 2025;29(20):4190-4204
BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.
3.Study on metabolites derived from Zhideke granules in rats in vivo
Jie LIANG ; Piaoxue ZHENG ; Huihua CHEN ; Chunyan HUANG ; Yanli LIANG ; Chunlian LU ; Jingjing XIE ; Yuming MA ; Jiawen PENG ; Lichun ZHAO ; Rilan CHEN
China Pharmacy 2024;35(2):172-178
OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group (Zhideke granules, 9.45 g/kg); they were given ultrapure water or relevant medicine, twice a day, every 6-8 h, for 3 consecutive days. Serum, urine and feces samples of rats were collected, and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules; their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules, 16 prototype components (i.g. irisflorentin, baicalin, chlorogenic acid) and 11 metabolites (i.g. hydration products of kaempferol or luteolin, methylation products of chlorogenic acid, and hydroxylation products of baicalin) were identified in serum, urine and feces of rats. Among them, 8 prototype components and 4 metabolites were identified in serum samples; 10 prototype components and 7 metabolites were identified in urine samples; 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin, irisflorentin,chlorogenic acid, and the main metabolic pathways included methylation, hydroxylation, glucuronidation.
4.Diagnosis and treatment of prostate mucosa adenocarcinoma under multidisciplinary diagnosis and treatment mode: 2 cases report and literature review
Peng WU ; Fuli WANG ; Jing ZHANG ; Jing REN ; Zhiyong QUAN ; Wanni XU ; Lichun WEI ; Weijun QIN
Journal of Modern Urology 2024;29(2):154-157
【Objective】 To explore the clinicopathological characteristics and comprehensive treatment strategies of prostate mucosa adenocarcinoma under multidisciplinary diagnosis and treatment (MDT) mode. 【Methods】 Data of two patients with typical prostate mucosa adenocarcinoma treated in our hospital during Sep.2020 and Apr.2023 were retrospectively analyzed. 【Results】 In case 1, the clinical manifestation was macroscopic hematuria; multiparametric magnetic resonance imaging (mpMRI) indicated solid prostatic nodules, clinical stage T4N1Mx; initial prostate specific antigen (PSA) was 1.2 ng/mL; 6868Ga-prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) suggested abnormal uptake of nuclear lesions in the prostate (SUV4.2-5.3); biopsy results indicated invasive mucinous adenocarcinoma.After prostate and pelvic field radiotherapy + androgen deprivation therapy (ADT) + antihypertensive treatment, lesions were significantly reduced, and hematuria symptoms were relieved.In case 2, the clinical manifestation was dysuria; initial PSA was 91.78 ng/mL; mpMRI suggested invasion of prostate mass into the bladder and clinical stage of T4N1M1b; 68Ga-PSMA PET/CT indicated prostate and pelvic lymph nodes, and multiple bone lesions showed increased nuclide uptake; biopsy results indicated prostate adenocarcinoma with mucinous adenocarcinoma.Initial endocrine treatment was performed.After 3 months, PSA was reduced to 0.083 ng/mL, and imaging showed the tumor was significantly reduced.Robotic-assisted laparoscopic tumor prostatectomy with extended pelvic lymph node dissection was performed, and endocrine adjuvant therapy was continued after surgery. 【Conclusion】 Prostate mucosa adenocarcinoma has different clinicopathological characteristics and prognosis from conventional acinar adenocarcinoma, and the whole-process management under MDT mode is of great value in the diagnosis and treatment of this disease.
5.Bioinformatics Analysis of Modified Lugen Formula in the Treatment of Influenza:Perspectives from the Virus-Host Interaction Network
Peng WU ; Yong JIANG ; Sha LI ; Wenyu WU ; Lichun JI ; Haidu HONG ; Gao ZHANG ; Huiting HUANG ; Xiaohong LIU ; Shaofeng ZHAN ; Yanni LAI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):358-367
Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.
6.Application of 68Ga-PSMA PET/CT in the precision treatment of prostate cancer
Peng WU ; Jianhua JIAO ; Chunjuan TIAN ; Shuaijun MA ; Lichun WEI ; Jing ZHANG ; Jing REN ; Daliang LIU ; Fuli WANG ; Weijun QIN
Chinese Journal of Urology 2021;42(Z1):63-66
We retrospectively analyzed the clinical characteristic of one patient with metastatic prostate cancer and the relative literatures were reviewed. A 40-year-old man was admitted and diagnosed as prostate cancer on March 20, 2018(T 4N 1M 1a) with prostate-specific antigen (PSA) at 47.99 ng/ml. The first 68Ga-PSMA PET/CT showed multiple nodular lesions in the bilateral peripheral bands of the prostate, multiple nodular lesions in the right apex, abnormal uptake of nuclides in multiple lymph nodes in the abdominal aortic wandering zone, the abdominal aortic bifurcation zone, and the bilateral iliac artery wandering zone at the level of the lumbar 2-5 vertebral body, and metastasis was considered. The patient was treated with six cycles of drug castration combined with antiandrogenic treatment and pre-operative system chemotherapy(docetaxel). Six months later, the PSA decreased to 0.225ng/ml. Robot-assisted laparoscopic prostatectomy and expanded pelvic lymph node dissection was performed. Postoperative total androgen blocking therapy was maintained, and PSA slowly increased. Ten months after operation, salvage radiotherapy for enlarged lymph nodes was performed in pelvic extension field, prostate tumor bed area and pelvic cavity. PSA remained stable for 7 months postradiotherapy, and then increased. The patient developed castration-resistant prostate cancer and was treated with triptorelin combined with abiraterone. PSA was decreased, and local radiotherapy was performed for new lymph node metastases in the neck. 68Ga-PSMA PET/CT could provide a decision-making basis for accurate clinical staging, therapeutic effect evaluation and distant metastatic lesions location with guiding value for the formulation of individualized treatment plans.
7.Analysis of visceral metastasis hormone sensitive prostate cancer: a case report and literature review
Peng WU ; Weijun QIN ; Yu LI ; Shuaijun MA ; Lichun WEI ; Jing ZHANG ; Jing REN ; Daliang LIU ; Fuli WANG ; Chunjuan TIAN
Chinese Journal of Urology 2021;42(Z1):67-71
Hormone-sensitive prostate cancer with visceral metastasis is a difficulty in clinical diagnosis and treatment. We treated a patient with hormone-sensitive prostate cancer with visceral metastasis and managed it under the multi-disciplinary treatment model (MDT). A 55-year-old man presented to the hospital complaining of increased prostate-specific antigen (PSA) found in the physical examination for 2 days. At admission, the PSA was 389.2ng/ml, and 68Ga-PSMA PET/CT showed metastatic malignant lesions of the prostate, with lymph node metastasis, lumbar vertebral metastases and liver tubercles. Transrectal prostate puncture biopsy: prostate adenocarcinoma, Gleason score of 4+ 5=9. The patient has no history of androgen deprivation therapy (ADT) and diagnosed as metastatic hormone-sensitive prostate cancer (mHSPC). Then the patient received total androgen blockade therapy (CAB regimen). After MDT discussion, metastatic prostate cancer was diagnosed based on the liver histopathology of percutaneous biopsy. After the second MDT discussion, the regimen was changed to abirone plus ADT. After 6 months, the blood PSA was controlled at a level between 0.003 to 0.006 ng/ml, and the testosterone was less than 2.5ng/dl. Re-examination of 68Ga-PSMA PET/CT showed that lower signal of radionuclide in all lesions, especially no more abnormal uptake lesions were identified in the liver.
8.Research on the learning curve of contrast-enhanced ultrasonography in sentinel lymph node of breast cancer
Juan LI ; Man LU ; Hui LI ; Xueqing CHENG ; Ling GUAN ; Yun LU ; Peng GU ; Jian LIU ; Wen CHENG ; Hua SHAO ; Weiwei ZHAN ; Juan LIU ; Lina TANG ; Zhongshi DU ; Yuhua ZHANG ; Shan WANG ; Chen YANG ; Qiuqing ZHENG ; Lichun YANG ; Saiping HAI
Chinese Journal of Ultrasonography 2018;27(9):800-804
Objective To investigate the learning curve of contrast-enhanced ultrasonography ( CEUS) in sentinel lymph node( SLN ) of breast cancer and provide a theoretical basis for leaners to learn SLN CEUS . Methods The multi-center study of SLN CEUS in breast cancer" was planned by Sichuan Cancer Hospital . According to the uniform inclusion and exclusion criteria , 511 patients with complete clinical data and follow-up results from 9 hospitals in Multi-center were included in this study . According to the inspection time ,the patients were divided into 3 groups named as group A ( 170 patients) ,group B ( 170 patients) and group C ( 171 patients ) ,respectively . The basic clinical data ,ultrasound imaging data , intraoperative and postoperative pathological findings of all patients were recorded . With the accumulation of cases examined ,analysis was performed to find the learning curve of the SLN CEUS examination time , SLN CEUS detection rate ,SLN CEUS surface marking accuracy rate and SLN CEUS diagnosis rate ,the learning curve was analyzed . Results ① There was no statistical significant difference in patients ages , tumors sizes ,tumors locations ,SLNs numbers and LCs numbers among the three groups( all P > 0 .05) . ②As the number of cases examined increases ,the examination time was reduced gradually ,but SLN detection rate ,surface marking accuracy and SLN diagnostic coincidence rate were increased gradually( F = 151 .75 , 1 .96 ,7 .49 ,5 .50 ; P = 0 .000 ,0 .143 ,0 .001 ,0 .005 ) . Conclusions The skill of the doctor is improved gradually when learning SLN CEUS . With the number of the cases increase ,the operating time of SLN CEUS is shorted ,and the SLN detection rate ,surface marking accuracy and SLN diagnostic coincidence rate of SLN-CEUS are gradually increased . It has an important clinical significance for beginners to learn the SLN CEUS technology .
9.Establishment and analysis on reliability and validity of nursing assistant requirements questionnaire of county hospital
Congxiang LIU ; Langjuan TANG ; Lichun YUE ; Yuyan PENG
Chinese Journal of Practical Nursing 2016;32(5):386-390
Objective To establish the questionnaire of nursing assistant requirements of county hospital, test and analyze its reliability and validity. Methods According to the nursing assistant requirements framework had been constructed, document literature and interview to develop a questionnaire item pool, then established the prequestionnaire after research group discussion and expert evaluation. 250 clinical nurses were selected for investigation. Then item analysis,factor analysis, correlation analysis and reliability analysis were applied to test the scale′s validity and reliability. Results The effective questionnaire was 224 copies. Questionnaire of nursing assistant requirements was consisted of 44 items, the factor analysis of the questionnaire identified six principal factors and explained for 53.225% total variances. Correlation coefficient between each dimension and the total scale was 0.532-0.794, the Cronbach α coefficient of each dimension was 0.789-0.910,the Cronbach α of whole scale and split- half coefficient were 0.923 and 0.868. Conclusions The questionnaire of nursing assistant requirements of county hospital has high reliability and validity.It can provide a scientific basis for county hospital to carry out nursing assistance.
10.Effect of Low Dose of Chicken Infectious Anemia Virus in Attenuated Vaccine on SPF Chicken Body Weight and Vaccine Immune Antibody.
Lichun FANG ; Xiaohan LI ; Zhihao REN ; Yang LI ; Yixin WANG ; Zhizhong CUI ; Shuang CHANG ; Peng ZHAO
Chinese Journal of Virology 2016;32(2):190-194
In order to observe the effect of the immune and weight of chickens after use the attenuated vaccine with low dose of chicken infectious anemia virus (CIAV). In this study, the effects of low dose of CIAV on the weight of SPF chickens and NDV antibody production were observed by simulated experiments. The results showed that 10 EID50 and 5 EID50 CIAV per plume attenuated NDV vaccines were used to cause the weight loss of SPF chickens. Compared with the use of the non contaminated vaccine group, it has significant difference. And NDV antibody levels compared with the use of the non contaminated groups also decreased after use the vaccine with two doses of CIAV contaminated. It has significant difference. A certain proportion of CIAV antibody positive was detected at the beginning of the second week after use the NDV vaccine with two doses of CIAV contaminated. The detection of a high proportion of CIAV nucleic acid was detected in the first week after the use of a contaminated vaccine. The results of the study demonstrate the effects of CIAV pollution on the production and immune function of SPF chickens, and it is suggested that increasing the detection of viral nucleic acid can help save time and improve the detection rate in the detection of exogenous virus contamination by SPF chicken test method.
Animals
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Antibodies, Viral
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immunology
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Chicken anemia virus
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genetics
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immunology
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physiology
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Chickens
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Circoviridae Infections
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immunology
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veterinary
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virology
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Poultry Diseases
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immunology
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virology
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Specific Pathogen-Free Organisms
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Vaccines, Attenuated
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administration & dosage
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genetics
;
immunology

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