1.Effect of Shenge Bushen Capsules and Its Polysaccharides and Flavonoids on Precocious Puberty in Young Mice
Hong SUN ; Fan LEI ; Chenggong LI ; Shixian HU ; Weihua WANG ; Bin REN ; Juan HAO ; Rui LUO ; Lijun DU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):95-103
ObjectiveTo explore the effect of Shenge Bushen Capsules (SBC) on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part, mice were divided into four groups: The control group and the low, medium, and high-dose SBC groups (234.7, 469.4, 938.7 mg·kg-1, respectively). In the second part, mice were divided into four groups: Control group, Pseudostellariae Radix polysaccharide (PRP) group, total flavonoids group, and SBC group, all receiving a dose of 469.4 mg·kg-1. After 7 days of administration, the vaginal opening of female mice and the descent of testes and scrotum in male mice, as well as the ovarian and testicular organ indices, were observed. After 4 weeks of administration, female and male mice were housed together for 2 days, and the pregnancy rate of females was monitored. After delivery, the pregnant female mice continued receiving the treatment for 4 weeks, and the sexual development of their offspring, including vaginal opening, testicular descent, and organ indices of ovaries and testes, was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group, there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration, the pregnancy rate in the low-dose group was significantly reduced (P<0.05), but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices, and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC, Pseudostellariae Radix polysaccharide, significantly reduced the vaginal opening in female mice after 7 days of administration (P<0.05). After 4 weeks, the serum estradiol levels of non-pregnant female mice were decreased (P<0.05), but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally, there were no significant effects on precocious puberty indicators, such as vaginal opening and testicular descent, in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice, and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.
2.Effect of Quercetin on Cuproptosis in Rheumatoid Arthritis Rats and Its Mechanism via SLC31A1/FDX1 Pathway
Haoruo YANG ; Qiuai KOU ; Junhua REN ; Guo YUAN ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):121-130
ObjectiveTo observe the influence and therapeutic effect of quercetin on cuproptosis in rheumatoid arthritis rats and to explore its possible mechanism based on the solute carrier family 31 member 1 (SLC31A1)/ferredoxin 1 (FDX1) pathway. MethodsSixty male SD rats were divided into six groups: A control group, a model group, high- and low-dose quercetin groups (150 and 50 mg·kg-1), a cuproptosis inhibitor (tetrathiomolybdate, TTM) group (10 mg·kg-1), and a methotrexate group (2 mg·kg-1), 10 rats in each group. Except for the control group, the model of rheumatoid arthritis (CIA) rats was established by type Ⅱ collagen induction method. After successful modeling, each drug group was intervened according to the corresponding dose of drugs, and the control group and the model group were given the same amount of normal saline by gavage, once a day, which lasted for 4 weeks. The swelling degree of rats' feet was observed, and the clinical arthritis scores were determined. The levels of serum rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), and ceruloplasmin (Cp) were detected by enzyme-linked immunosorbent assay (ELISA). The content of copper ion (Cu), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in joint tissue was detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of joint tissue. The levels of reactive oxygen species (ROS) and dihydrolipoic acid transacetylase (DLAT) were detected by immunofluorescence (IF). The protein and mRNA expression of SLC31A1, FDX1, lipoic acid synthase (LIAS), heat shock protein 70 (HSP70), pyruvate dehydrogenase E1 subunit β (PDHB), and copper transporting P-type ATPase β (ATP7B) was detected by immunohistochemistry (IHC) and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared to the control group, the model group exhibited joint swelling and deformity, significantly increased clinical arthritis scores, obvious bone destruction, synovial hyperplasia, and inflammatory cell infiltration in joint tissue. In addition, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp showed significant elevation, while the level of IL-10 was significantly reduced. The levels of Cu, MDA, ROS, and DLAT in joint tissue were markedly increased, whereas SOD and GSH content was significantly decreased. The protein and mRNA expression of SLC31A1 and HSP70 was significantly up-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was significantly down-regulated (P<0.01). Compared to the model group, each treatment group exhibited varying degrees of improvement in joint swelling and deformation as well as clinical arthritis scores in rats. Additionally, there was a reduction in joint bone destruction, inflammatory cell infiltration, and synovial hyperplasia in rats. Furthermore, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp significantly decreased, while the level of IL-10 increased significantly. In joint tissue, the levels of Cu, MDA, ROS, and DLAT showed significant decreases, while SOD and GSH content exhibited significant increases. The protein and mRNA expression of SLC31A1 and HSP70 was down-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was up-regulated (P<0.05). ConclusionQuercetin effectively reduces synovial hyperplasia and inflammatory infiltration in rats with rheumatoid arthritis, thereby alleviating pathological damage to joint tissue. This effect may be attributed to the blockade of the SLC31A1/FDX1 signaling pathway activation and inhibition of excessive cuproptosis.
3.Bioinformatics Reveals Mechanism of Xiezhuo Jiedu Precription in Treatment of Ulcerative Colitis by Regulating Autophagy
Xin KANG ; Chaodi SUN ; Jianping LIU ; Jie REN ; Mingmin DU ; Yuan ZHAO ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):166-173
ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis (UC) by bioinformatics and animal experiments. MethodsThe differentially expressed genes (DEGs) in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus (GEO), and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes (DEARGs). DEARGs were imported into Metascape and STRING, respectively, for gene ontology/Kyoto Encyclopedia of Genes and Genomics (GO/KEGG) enrichment analysis and protein-protein interaction (PPI) analysis. Finally, 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic curve (ROC) analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-, medium-, and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 (Caspase-1), cathepsin B (CTSB), C-C motif chemokine-2 (CCL2), CXC motif receptor 4 (CXCR4), and hypoxia-inducing factor-1α (HIF-1α) in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction, respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis, LASSO regression, and ROC analysis, the core DEARGs (Caspase-1, CCL2, CTSB, and CXCR4) were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells, M0 macrophages, M1 macrophages, and dendritic cells in the colonic mucosal tissue of UC patients had significant differences, and core DEARGs had significant correlations with these immune cells. This result, combined with the prediction results of network pharmacology, suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group, the model group showed up-regulated protein and mRNA levels of caspase-1, CCL2, CTSB, CXCR4, and HIF-1α, which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1, CCL2, CTSB, and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.
4.Intense pulsed light combined with Yuyin Runmu formula fumigation and meibomian gland massage for the treatment of meibomian gland dysfunction-related dry eye
Maodan RAN ; Lu JIN ; Gang REN
International Eye Science 2025;25(1):157-161
AIM: To investigate the effect of intense pulsed light(IPL)combined with Yuyin Runmu formula fumigation and meibomian gland massage on the treatment of patients with meibomian gland dysfunction(MGD)-related dry eye.METHODS: Prospectively selected 198 cases(396 eyes)of MGD-related dry eye patients admitted to our hospital from November 2021 to November 2023, and they were randomly divided into 99 cases(198 eyes)in control group treated with fumigation of Yuyin Runmu formula and meibomian gland massage, and 99 cases(198 eyes)in observation group treated with combined IPL on the basis of the control group. The efficacy of the two groups was compared, as well as the changes in the levels of ocular indexes [tear film break-up time(BUT), Schirmer I test(SⅠt)], visual quality [objective scattering index(OSI), Strehl ratio(SR), and modulation transfer function(MTF)], lipid layer thickness(LLT)of the tear film, and changes in tear fluid levels of inflammatory factors [tumour necrosis factor-α(TNF-α)and transforming growth factor-beta 1(TGF-β1)].RESULTS: All the patients completely received the treatment and follow-up. The levels of BUT, SⅠt, SR, MTF, and LLT increased and the levels of OSI, TNF-α, and TGF-β1 decreased in the two groups at 2 mo after treatment(all P<0.001), and the observation group was more favourable(all P<0.001).CONCLUSION: IPL combined with Yuyin Runmu formula fumigation and meibomian gland massage is effective in treating MGD-related dry eye, improving patients' ocular parameters, visual quality, and LLT, and decreasing the levels of inflammatory factors in the tear fluid.
5.Knowledge map and visualization analysis of pulmonary nodule/early-stage lung cancer prediction models
Yifeng REN ; Qiong MA ; Hua JIANG ; Xi FU ; Xueke LI ; Wei SHI ; Fengming YOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):100-107
Objective To reveal the scientific output and trends in pulmonary nodules/early-stage lung cancer prediction models. Methods Publications on predictive models of pulmonary nodules/early lung cancer between January 1, 2002 and June 3, 2023 were retrieved and extracted from CNKI, Wanfang, VIP and Web of Science database. CiteSpace 6.1.R3 and VOSviewer 1.6.18 were used to analyze the hotspots and theme trends. Results A marked increase in the number of publications related to pulmonary nodules/early-stage lung cancer prediction models was observed. A total of 12581 authors from 2711 institutions in 64 countries/regions published 2139 documents in 566 academic journals in English. A total of 282 articles from 1256 authors were published in 176 journals in Chinese. The Chinese and English journals which published the most pulmonary nodules/early-stage lung cancer prediction model-related papers were Journal of Clinical Radiology and Frontiers in Oncology, respectively. Chest was the most frequently cited journal. China and the United States were the leading countries in the field of pulmonary nodules/early-stage lung cancer prediction models. The institutions represented by Fudan University had significant academic influence in the field. Analysis of keywords revealed that multi-omics, nomogram, machine learning and artificial intelligence were the current focus of research. Conclusion Over the last two decades, research on risk-prediction models for pulmonary nodules/early-stage lung cancer has attracted increasing attention. Prognosis, machine learning, artificial intelligence, nomogram, and multi-omics technologies are both current hotspots and future trends in this field. In the future, in-depth explorations using different omics should increase the sensitivity and accuracy of pulmonary nodules/early-stage lung cancer prediction models. More high-quality future studies should be conducted to validate the efficacy and safety of pulmonary nodules/early-stage lung cancer prediction models further and reduce the global burden of lung cancer.
6.Recent advances in the application of three dimensional reconstruction techniques in surgical treatment of early lung cancer
Tao LONG ; Zhengbing REN ; Aizhong SHAO ; Zhicheng HE ; Weibing WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):121-128
Lung cancer is the leading cause of death worldwide. With the prevalence of CT screening and early diagnosis and treatment of lung cancer in China, more and more patients with early-stage lung cancer characterized with ground-glass opacity are discovered and urgently require treatment, which poses a significant challenge to surgeons. As an emerging technology, three dimensional reconstruction technology plays a crucial auxiliary role in clinical work. This review aims to briefly introduce this technology, focusing on its latest advances in surgical applications in early lung cancer screening, malignant risk assessment, and perioperative period application and medical education.
7.Recognition of breath odor map of benign and malignant pulmonary nodules and Traditional Chinese Medicine syndrome elements based on electronic nose combined with machine learning: An observational study in a single center
Shiyan TAN ; Qiong ZENG ; Hongxia XIANG ; Qian WANG ; Xi FU ; Jiawei HE ; Liting YOU ; Qiong MA ; Fengming YOU ; Yifeng REN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):185-193
Objective To explore the recognition capabilities of electronic nose combined with machine learning in identifying the breath odor map of benign and malignant pulmonary nodules and Traditional Chinese Medicine (TCM) syndrome elements. Methods The study design was a single-center observational study. General data and four diagnostic information were collected from 108 patients with pulmonary nodules admitted to the Department of Cardiothoracic Surgery of Hospital of Chengdu University of TCM from April 2023 to March 2024. The patients' TCM disease location and nature distribution characteristics were analyzed using the syndrome differentiation method. The Cyranose 320 electronic nose was used to collect the odor profiles of oral exhalation, and five machine learning algorithms including random forest (RF), K-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM), and eXtreme gradient boosting (XGBoost) were employed to identify the exhaled breath profiles of benign and malignant pulmonary nodules and different TCM syndromes. Results (1) The common disease locations in pulmonary nodules were ranked in descending order as liver, lung, and kidney; the common disease natures were ranked in descending order as Yin deficiency, phlegm, dampness, Qi stagnation, and blood deficiency. (2) The electronic nose combined with the RF algorithm had the best efficacy in identifying the exhaled breath profiles of benign and malignant pulmonary nodules, with an AUC of 0.91, accuracy of 86.36%, specificity of 75.00%, and sensitivity of 92.85%. (3) The electronic nose combined with RF, LR, or XGBoost algorithms could effectively identify the different TCM disease locations and natures of pulmonary nodules, with classification accuracy, specificity, and sensitivity generally exceeding 80.00%.Conclusion Electronic nose combined with machine learning not only has the potential capabilities to differentiate the benign and malignant pulmonary nodules, but also provides new technologies and methods for the objective diagnosis of TCM syndromes in pulmonary nodules.
8.Analysis of plasma metabonomic characteristics of type 2 diabetes mellitus patients with turbid toxin accumulation syndrome
Ziqi ZHAO ; Pai PANG ; Yue REN ; Bin WANG ; Yuntao MA ; Qianjing YANG ; Shentao WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):34-42
Objective:
To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome.
Methods:
One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website.
Results:
There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways.
Conclusion
Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.
9.The distribution pattern of traditional Chinese medicine syndromes and influencing factors for primary liver cancer: An analysis of 415 cases
Zhiyao SHI ; Xiaofei FAN ; Yu GAO ; Shaojian REN ; Shiyu WU ; Xixing WANG
Journal of Clinical Hepatology 2025;41(1):84-91
ObjectiveTo investigate the influencing factors for traditional Chinese medicine (TCM) syndromes of primary liver cancer, and to provide a theoretical basis for the TCM syndrome differentiation and standardized treatment of liver cancer. MethodsTCM syndrome differentiation was performed for 415 patients who were admitted to Shanxi Institute of Traditional Chinese Medicine and were diagnosed with primary liver cancer based on pathological or clinical examinations from January 2019 to December 2023. The chi-square test was used for comparison of categorical data between groups, and the unordered polytomous logistic regression model was used to investigate the influencing factors for TCM syndromes of liver cancer. ResultsThe common initial symptoms of the 415 patients with primary liver cancer included pain in the liver area (31.81%), abdominal distension (25.30%), abdominal pain (15.18%), and weakness (13.98%), and the main clinical symptoms included poor appetite (70.84%), fatigue (69.16%), pain in the liver area (67.47%), poor sleep (59.04%), abdominal distension (53.01%), and constipation (52.53%). There were significant differences in TCM syndromes between patients with different sexes, courses of the disease, clinical stages, Child-Pugh classes, presence or absence of intrahepatic and extrahepatic metastasis, and presence or absence of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (all P<0.05). The logistic regression analysis showed that male sex was a risk factor for damp-heat accumulation (odds ratio [OR]=2.036, P=0.048) and the syndrome of spleen-kidney Yang deficiency (OR=5.240, P<0.001); a course of disease of<1 year was a risk factor for damp-heat accumulation (OR=2.837, P=0.004) and syndrome of Qi stagnation and blood stasis (OR=2.317, P=0.021), but it was a protective factor against syndrome of spleen-kidney Yang deficiency (OR=0.385, P=0.005); Child-Pugh class A/B was a protective factor against liver-kidney Yin deficiency (OR=0.079, P<0.001); intrahepatic metastasis was a risk factor for liver-kidney Yin deficiency (OR=5.117, P=0.003) and syndrome of spleen-kidney Yang deficiency (OR=3.303, P=0.010); TACE was a protective factor against liver-kidney Yin deficiency (OR=0.171, P<0.001) and syndrome of spleen-kidney Yang deficiency (OR=0.138, P<0.001); radiofrequency ablation was a risk factor for damp-heat accumulation (OR=4.408, P<0.001) and liver-kidney Yin deficiency (OR=32.036, P<0.001). ConclusionSex, course of disease, Child-Pugh class, intrahepatic metastasis, TACE, and radiofrequency ablation are the main influencing factors for TCM syndromes of liver cancer.
10.Association of the adipokine Chemerin with the development and progression of liver fibrosis
Xinyuan ZHANG ; Nuoqi ZHANG ; Guohui YU ; Wenshuai REN ; Yaling WANG
Journal of Clinical Hepatology 2025;41(1):164-169
Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis, and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine, Chemerin participates in the metabolism of glucose and lipids and inflammation, and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis, suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis, in order to provide new ideas for the diagnosis and treatment of liver fibrosis.


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