1.Screening of biomarkers for fibromyalgia syndrome and analysis of immune infiltration
Yani LIU ; Jinghuan YANG ; Huihui LU ; Yufang YI ; Zhixiang LI ; Yangfu OU ; Jingli WU ; Bing WEI
Chinese Journal of Tissue Engineering Research 2025;29(5):1091-1100
BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.
2.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
3.Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
Yuzhuo WEI ; Li LIU ; Shu BU ; Yongqi WANG ; Zhiwei MIAO ; Yi XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):40-50
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos (DH) in the treatment of ulcerative colitis (UC) using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium (DSS). The experimental groups were the normal group, the model group, the salazosulfapyridine group (100 mg·kg-1), and the low, medium, and high dose groups of DH (1.2, 2.4, and 4.8 g·kg-1). The efficacy of the treatment was assessed through the general condition of the mice, histopathological examination, and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA (mRNA) detection of colonic angiogenesis-related mediators, vascular endothelial growth factor (VEGF) immunohistochemistry, microvessel density (MVD) detection, and transmission electron microscopy. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH, of which the core targets were tumor protein 53 (TP53), JUN, interleukin (IL)-6, Akt1, and tumor necrosis factor (TNF). Compared with the normal group, mice in the model group showed significant weight loss, colon shortening, and high DAI score, increased expression of inflammatory factors IL-6, IL-1β, and TNF-α, as well as increased mRNA expression levels of angiogenesis-related mediators VEGF, vascular cell adhesion molecule 1 (VCAM1), angiotensin 1 (Ang1), matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased, and the protein expression of the PI3K/Akt pathway was increased (P<0.05). The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group, mice in the DH groups had significantly reduced weight loss and colon shortening, lower DAI scores, and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition, there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway (P<0.05). ConclusionNetwork pharmacology, molecular docking, and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC, and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
4.Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
Yuzhuo WEI ; Li LIU ; Shu BU ; Yongqi WANG ; Zhiwei MIAO ; Yi XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):40-50
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos (DH) in the treatment of ulcerative colitis (UC) using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium (DSS). The experimental groups were the normal group, the model group, the salazosulfapyridine group (100 mg·kg-1), and the low, medium, and high dose groups of DH (1.2, 2.4, and 4.8 g·kg-1). The efficacy of the treatment was assessed through the general condition of the mice, histopathological examination, and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA (mRNA) detection of colonic angiogenesis-related mediators, vascular endothelial growth factor (VEGF) immunohistochemistry, microvessel density (MVD) detection, and transmission electron microscopy. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH, of which the core targets were tumor protein 53 (TP53), JUN, interleukin (IL)-6, Akt1, and tumor necrosis factor (TNF). Compared with the normal group, mice in the model group showed significant weight loss, colon shortening, and high DAI score, increased expression of inflammatory factors IL-6, IL-1β, and TNF-α, as well as increased mRNA expression levels of angiogenesis-related mediators VEGF, vascular cell adhesion molecule 1 (VCAM1), angiotensin 1 (Ang1), matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased, and the protein expression of the PI3K/Akt pathway was increased (P<0.05). The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group, mice in the DH groups had significantly reduced weight loss and colon shortening, lower DAI scores, and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition, there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway (P<0.05). ConclusionNetwork pharmacology, molecular docking, and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC, and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
5.Study on toxicity-reducing and efficacy-enhancing effects of Polygala tenuifolia compatibility on sand-ironing Strychnos nux-vomica
Yi SUI ; Guo FENG ; Gang LIU ; Keyan LIU ; Xuehao WEI ; Minggang TENG ; Wei LI ; Caiyao HAN ; Yan LEI
China Pharmacy 2025;36(10):1197-1201
OBJECTIVE To explore the effects of Polygala tenuifolia compatibility on toxicity, anti-inflammatory and analgesic efficacy of sand-ironing Strychnos nux-vomica (SS). METHODS The preparation of SS single decoction, SS-P. tenuifolia core-removed (PC) (1∶2.5) or (1∶5) combined decoction, and SS-PC (1∶5) mixture were carried out to investigate their median lethal dose (LD50). Using aspirin as positive control, the number of writhing movements, analgesic rate, pain latency, ear swelling degree and inflammation inhibition rate induced by the above-mentioned medicinal liquids in mice were compared. The contents of the active and toxic components, strychnine and brucine, in the above-mentioned medicinal liquids were also determined. RESULTS The LD50 values of SS single decoction, SS-PC (1∶2.5) combined decoction, SS-PC (1∶5) combined decoction and SS- PC (1∶5) mixture were 302.00, 614.47, 1 445.44 and 1 778.28 mg/kg, respectively. Compared with control group, the number of writhing movements and ear swelling degree in the mice of the above-mentioned medicinal liquid groups were reduced or decreased significantly (P<0.05 or P<0.01); pain latency [at 90 and 120 minutes in the SS single decoction group, at 60 and 90 minutes in the SS-PC (1∶2.5) combined decoction group, and at 60,90, 120 minutes in the SS-PC (1∶5) combined decoction group and SS-PC (1∶5) mixture group] was significantly prolonged (P<0.05 or P<0.01); analgesic rates of the respective medicinal liquids were 39.30%, 70.87%, 80.00% and 82.46%, and inflammation inhibition rates were 38.08%,TD 57.89%, 76.47% and 50.46%; analgesic and anti-inflammatory effects of combined decoction and mixture were generally better than those of the single decoction (P<0.05 or P<0.01). In the above-mentioned four medicinal liquids, the total contents of strychnine were 0.71%, 0.42%, 0.47% and 0.64%, and the total contents of brucine were 0.88%, 0.63%, 0.57% and 0.88%, respectively. CONCLUSIONS The combination of P. tenuifolia can reduce the toxicity of SS and enhance its anti-inflammatory and analgesic effects. Moreover, there is a tendency for the toxicity-reducing and efficacy-enhancing effects to increase with the increasing dosage of P. tenuifolia. Additionally, the combined decoction of SS and P. tenuifolia can reduce the contents of the active and toxic components, strychnine and brucine, in SS.
6.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
7.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
8.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
9.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
10.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

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