1.Effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis:machine learning and 16S rDNA analysis
Fucheng GU ; Meixin YANG ; Weixin WU ; Weijun CAI ; Yangyi QIN ; Mingyi SUN ; Jian SUN ; Qiudong GENG ; Nan LI
Chinese Journal of Tissue Engineering Research 2026;30(4):1058-1072
BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P<0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P<0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P<0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.
2.Effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis:machine learning and 16S rDNA analysis
Fucheng GU ; Meixin YANG ; Weixin WU ; Weijun CAI ; Yangyi QIN ; Mingyi SUN ; Jian SUN ; Qiudong GENG ; Nan LI
Chinese Journal of Tissue Engineering Research 2026;30(4):1058-1072
BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P<0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P<0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P<0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.
3.Consensus on the use of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for cancer pain management
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
4.Value of a multimodal 18F-FDG PET/CT model in the differentiation of benign and malignant pulmonary lesions
Ruihe LAI ; Yuzhi GENG ; Jian HE ; Dandan SHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(9):525-529
Objective:To establish a combined model of tumor heterogeneity metabolic parameters using 18F-FDG PET/CT and explore its value in differentiating benign from malignant pulmonary lesions. Methods:A total of 251 patients (157 males, 94 females; age 15-88 years) who were diagnosed with malignant lung lesions by 18F-FDG PET/CT and with definitive pathological results at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2017 to February 2024 were retrospectively enrolled. Analysis was conducted on clinical data, traditional parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of primary lesions on 18F-FDG PET/CT, and intra-tumoral metabolic heterogeneity index (HI; such as cumulative SUV volume histogram AUC (AUC-CSH), linear regression slope, CV). AUC-CSH and CV were calculated using SUV thresholds of 2.5 and 40%SUV max. Logistic univariate and multivariate regression analyses were used to extract independent predictors in clinical features and PET/CT parameters for the differential diagnosis of pulmonary lesions. A multi-parameter combined model was established through logistic regression and validated for diagnostic efficacy using ROC curve analysis. Results:Among 251 patients, 101 were benign and 150 were malignant. In univariate analysis, gender, age, tumor markers, spiculation sign, lobulation sign, vessel convergence sign, air bronchogram, long diameter, short diameter, SUV max, AUC-CSH 2.5, AUC-CSH 40%, CV2.5, and CV40% were predictive factors for the diagnosis of benign and malignant tumors (odds ratio ( OR): 0.57-17.39, all P<0.05). In multivariate analysis, gender, age, tumor markers, lobulation sign, vessel convergence sign, SUV max, AUC-CSH 40%, and CV40% were independent predictors for the diagnosis of benign and malignant tumors ( OR: 2.30-13.18, all P<0.05). The AUC, sensitivity, specificity, and accuracy of the multi-parameter combined model established with the above independent predictors were 0.89, 77.33%(116/150), 84.16%(85/101), 80.08%(201/251), respectively. Conclusion:18F-FDG PET/CT multi-parameter combined model has high value in the differentiation of benign and malignant pulmonary lesions.
5.The application value of digital PCR and next-generation sequencing technology in the etiological diagnosis of sepsis patients
Jian SHI ; Jing LEI ; Zeshi LIU ; Chaoliang XIONG ; Tian LI ; Yan GENG
Chinese Journal of Microbiology and Immunology 2025;45(3):256-263
Objective:To explore the value of droplet digital PCR (ddPCR) and next-generation sequencing (NGS) technology in the pathogenetic diagnosis of sepsis patients, and to provide a reference basis for the early diagnosis of sepsis.Methods:A retrospective analysis was used to collect the clinical data of 53 patients with suspected sepsis admitted to the intensive care unit (ICU) of the Second Affiliated Hospital of Xi'an Jiaotong University from February to August 2023, and the blood was collected for blood culture, ddPCR and NGS detection simultaneously.Results:After excluding viral infections, the blood culture positive rate was 18.87%(10/53), the ddPCR positive rate was 47.17% (25/53), and the NGS positive rate was 41.51%(22/53). When using the ddPCR detection range as a reference, the ddPCR positivity rate was 98.11% (52/53), while the NGS positivity rate was 84.91%(45/53). There was a statistically significant difference in the positivity rate between the two groups ( P<0.05). Using blood culture as a reference, the sensitivity (60.00% vs 70.00%) and specificity (65.11% vs 69.77%) of ddPCR and NGS were in good agreement. In terms of pathogen detection, NGS had a wider detection range than ddPCR (34 species vs 21 species), and the difference was statistically significant (χ 2=55.000, P<0.001). In terms of time-consumption, blood culture took 66.93 h on average, while ddPCR was faster than NGS (about 4 h vs 20 h ). In terms of antimicrobial resistance (AMR) gene detection, five resistant strains were detected by both ddPCR and NGS, ddPCR detected two AMR genes, namely blaKPC and mecA, while NGS detected five AMR genes. Among them, except for blaKPC which was detected outside the target range in ddPCR, the other four AMR genes were also detected by ddPCR. Conclusions:Compared with blood culture, ddPCR and NGS have good application value in the etiological diagnosis of sepsis. Specifically, ddPCR has a higher detection rate of pathogens and takes less time. On the other hand, NGS has a wider detection range, especially for the discovery of some rare bacteria or pathogens that are difficult to be cultured routinely.
6.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
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Drugs, Chinese Herbal/therapeutic use*
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Hypertension/pathology*
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Renin-Angiotensin System/drug effects*
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Rats, Inbred SHR
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Oxidative Stress/drug effects*
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Male
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Rats, Inbred WKY
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Blood Pressure/drug effects*
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Myocardium/pathology*
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Rats
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Inflammation/pathology*
7.Triptolide Ameliorates Collagen-Induced Arthritis and Bleomycin-Induced Pulmonary Fibrosis in Rats by Suppressing IGF1-Mediated Epithelial Mesenchymal Transition.
Pei-Pei LU ; Lan YAN ; Qi GENG ; Lin LIN ; Lu-Lu ZHANG ; Chang-Qi SHI ; Peng-Cheng ZHAO ; Xiao-Meng ZHANG ; Jian-Yu SHI ; Cheng LYU
Chinese journal of integrative medicine 2025;31(12):1069-1077
OBJECTIVE:
To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM.
METHODS:
Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms.
RESULTS:
The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05).
CONCLUSION
TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals
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Pulmonary Fibrosis/complications*
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Bleomycin/adverse effects*
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Phenanthrenes/pharmacology*
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Male
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Rats, Sprague-Dawley
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Diterpenes/pharmacology*
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Epoxy Compounds/therapeutic use*
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Arthritis, Experimental/complications*
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Insulin-Like Growth Factor I/metabolism*
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Rats
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Lung/physiopathology*
8.UPLC-Q-TOF-MS combined with network pharmacology reveals effect and mechanism of Gentianella turkestanorum total extract in ameliorating non-alcoholic steatohepatitis.
Wu DAI ; Dong-Xuan ZHENG ; Ruo-Yu GENG ; Li-Mei WEN ; Bo-Wei JU ; Qiang HOU ; Ya-Li GUO ; Xiang GAO ; Jun-Ping HU ; Jian-Hua YANG
China Journal of Chinese Materia Medica 2025;50(7):1938-1948
This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals
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Non-alcoholic Fatty Liver Disease/genetics*
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Mice
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Network Pharmacology
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Male
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Drugs, Chinese Herbal/administration & dosage*
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Chromatography, High Pressure Liquid
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Liver/metabolism*
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Mice, Inbred C57BL
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Humans
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Mass Spectrometry
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Tumor Necrosis Factor-alpha/metabolism*
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Disease Models, Animal
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Molecular Docking Simulation
9.Predictive value of a combined model for lymph node metastasis in NSCLC based on primary lesion radiomics from 18F-FDG PET/CT
Ruihe LAI ; Yue TENG ; Jian RONG ; Dandan SHENG ; Yuzhi GENG ; Jianxin CHEN ; Chong JIANG ; Chongyang DING ; Zhengyang ZHOU
Journal of International Oncology 2025;52(3):144-151
Objective:To evaluate the value of a combined model based on primary lesion 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT radiomics for predicting lymph node metastasis in non-small cell lung cancer (NSCLC) . Methods:A retrospective analysis was conducted on the clinical data of 203 NSCLC patients who underwent pre-treatment PET/CT imaging at Nanjing Drum Tower Hospital from June 2013 to July 2023. Patients were randomly assigned to the training set ( n=142) and the validation set ( n=61) at a ratio of 7∶3. A predictive model was developed in the training set, and its predictive performance and clinical application value were assessed in both the training and validation sets. Traditional PET/CT parameters and PET/CT radiomics features of the primary lesion were obtained by 3D-slicer software. Least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting were performed to extract features. Support vector machine was used to construct a radiomics score (Radscore). Univariate and multivariate logistic regression analysis was used to predict the influencing factors of lymph node metastasis in NSCLC patients and to establish models. Predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves and clinical application value was assessed by calibration curves and decision curve analysis (DCA) . Results:Among 203 NSCLC patients, 116 had lymph node metastasis, with 64 cases in the training set and 52 cases in the validation set. Three complementary classical machine learning methods were used for feature screening, and finally 10 radiomics features were obtained. The optimal threshold for Radscore-PET was 0.43 and the optimal threshold for Radscore-CT was 0.39. Univariate analysis showed that, sex ( OR=0.48, 95% CI: 0.24-0.95, P=0.036), tumor marker levels ( OR=3.81, 95% CI: 1.84-7.91, P<0.001), long diameter of tumor ( OR=2.56, 95% CI: 1.27-5.16, P=0.009), short diameter of tumor ( OR=3.73, 95% CI: 1.75-7.92, P=0.001), vacuolar sign ( OR=0.32, 95% CI: 0.12-0.86, P=0.024), ring-like metabolism ( OR=3.67, 95% CI: 1.33-10.13, P=0.012), maximum standardized uptake value (SUV max) ( OR=6.57, 95% CI: 3.03-14.25, P<0.001), metabolic tumor volume (MTV) ( OR=2.91, 95% CI: 1.43-5.92, P=0.003), total lesion glycolysis (TLG) ( OR=4.23, 95% CI: 2.08-8.59, P<0.001), Radscore-PET ( OR=21.93, 95% CI: 9.04-53.20, P<0.001) and Radscore-CT ( OR=13.72, 95% CI: 6.12-30.76, P<0.001) were all influencing factors for predicting lymph node metastasis in NSCLC patients. Multivariate analysis showed that, tumor marker levels ( OR=2.55, 95% CI: 1.11-5.90, P=0.028), vacuolar sign ( OR=0.26, 95% CI: 0.08-0.83, P=0.023), SUV max ( OR=5.94, 95% CI: 1.99-17.75, P=0.001), Radscore-PET ( OR=25.51, 95% CI: 5.92-110.22, P<0.001), and Radscore-CT ( OR=8.68, 95% CI: 2.73-27.61, P<0.001) were independent influencing factors for predicting lymph node metastasis in patients with NSCLC. Based on the above independent influencing factors, models were constructed: the traditional model (tumor marker levels, vacuolar sign, SUV max), the PET model (SUV max, Radscore-PET), the CT model (vacuolar sign, Radscore-CT), and the combined model (tumor marker levels, vacuolar sign, SUV max, Radscore-PET, Radscore-CT). ROC curve analysis showed that, the area under curve (AUC) of the traditional, PET, CT, and combined models in the training set were 0.75 (95% CI: 0.67-0.82), 0.90 (95% CI: 0.84-0.95), 0.85 (95% CI: 0.78-0.90), and 0.94 (95% CI: 0.88-0.97), respectively. The predictive value of the combined model was higher than that of the traditional model ( Z=5.01, P<0.001), the PET model ( Z=1.99, P=0.047), and the CT model ( Z=3.25, P=0.001). In the validation set, the AUCs for the traditional model, PET model, CT model, and combined model were 0.65 (95% CI: 0.52-0.77), 0.86 (95% CI: 0.74-0.93), 0.85 (95% CI: 0.73-0.93), and 0.90 (95% CI: 0.80-0.96), respectively. The predictive value of the combined model was superior to that of the traditional model ( Z=3.23, P=0.001). The sensitivity and specificity of the combined model in the training set were 84.37% and 91.03%, while in the validation set, the sensitivity and specificity were 82.61% and 94.74%, respectively. Calibration curves showed a good agreement between the predicted and actual probabilities in both the training and validation sets. DCA showed that the combined models had good discriminative ability in both the training and validation sets. Conclusions:Tumor marker levels, vacuolar sign, SUV max, Radscore-PET, and Radscore-CT are all independent influencing factors for predicting lymph node metastasis in patients with NSCLC. The combined model based on these factors demonstrates excellent predictive performance and clinical application value for predicting lymph node metastasis in NSCLC.
10.Prognostic value of 18F-FDG PET/CT metabolic parameters in small cell lung cancer
Ruihe LAI ; Dandan SHENG ; Jian HE ; Chongyang DING ; Yuzhi GENG
Journal of International Oncology 2025;52(10):614-620
Objective:To evaluate the prognostic value of 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT metabolic parameters in small cell lung cancer (SCLC) . Methods:A retrospective analysis was conducted on the clinical and imaging data of 156 SCLC patients, who underwent 18F-FDG PET/CT imaging and were diagnosed by histopathological examination at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from September 2013 to February 2024. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), linear regression slope, area under the curve of cumulative standard uptake value (SUV) volume histogram (AUC-CSH), and coefficient of variation (CV) were calculated using LIFEx software with different SUV thresholds. Univariate and multivariate analyses were performed using Cox proportional hazards model. Patient stratification was based on the critical values determined by receiver operator characteristic (ROC) curve analysis. The survival curve was plotted using the Kaplan-Meier method and log-rank test was performed. Results:Univariate analysis showed that MTV 40% ( HR=2.91, 95% CI: 1.55-5.47, P=0.001), MTV 60% ( HR=2.31, 95% CI: 1.29-4.17, P=0.005), TLG 40% ( HR=2.07, 95% CI: 1.19-3.60, P=0.010), linear regression slope ( HR=0.45, 95% CI: 0.26-0.79, P=0.005), and CV 40% ( HR=0.27, 95% CI: 0.08-0.84, P=0.024) were factors affecting progression-free survival (PFS) in SCLC patients. MTV 40% ( HR=1.98, 95% CI: 1.22-3.22, P=0.005), MTV 60% ( HR=1.80, 95% CI: 1.12-2.88, P=0.015), MTV 80% ( HR=1.71, 95% CI: 1.08-2.74, P=0.024), TLG 40% ( HR=3.68, 95% CI: 1.59-8.49, P=0.002), linear regression slope ( HR=0.49, 95% CI: 0.30-0.80, P=0.004), and AUC-CSH 80% ( HR=0.44, 95% CI: 0.23-0.84, P=0.013) were found to be factors affecting overall survival (OS) in SCLC patients. Multivariate analysis revealed that MTV 40% ( HR=4.76, 95% CI: 1.11-20.50, P=0.036) was an independent factor influencing PFS, and TLG 40% ( HR=3.19, 95% CI: 1.02-9.92, P=0.046) was an independent factor influencing OS in SCLC patients. ROC curve analysis identified the optimal cutoff value for MTV 40% in predicting PFS as 5.5cm 3 and the optimal cutoff value for TLG 40% in predicting OS as 41.5 g in SCLC patients. Survival analysis showed that patients with MTV 40%≤5.5 cm 3 ( n=33) had a median PFS that was not reached, while patients with MTV 40%>5.5 cm 3 ( n=123) had a median PFS of 10.3 months, with a statistically significant difference ( χ2=12.09, P=0.001). For patients with TLG 40%≤41.5 g ( n=35), the median OS was not reached, whereas for TLG 40%>41.5 g ( n=121), the median OS was 31.6 months, with a statistically significant difference ( χ2=10.55, P=0.001) . Conclusions:The 18F-FDG PET/CT metabolic parameter MTV 40% is an independent factor influencing PFS, while TLG 40% is an independent factor influencing OS in SCLC patients. The above two parameters may serve as indicators for assessing the prognosis of SCLC patients.

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