1.Predicting Hepatocellular Carcinoma Using Brightness Change Curves Derived From Contrast-enhanced Ultrasound Images
Ying-Ying CHEN ; Shang-Lin JIANG ; Liang-Hui HUANG ; Ya-Guang ZENG ; Xue-Hua WANG ; Wei ZHENG
Progress in Biochemistry and Biophysics 2025;52(8):2163-2172
ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.
2.The systemic inflammatory response index as a risk factor for all-cause and cardiovascular mortality among individuals with coronary artery disease: evidence from the cohort study of NHANES 1999-2018.
Dao-Shen LIU ; Dan LIU ; Hai-Xu SONG ; Jing LI ; Miao-Han QIU ; Chao-Qun MA ; Xue-Fei MU ; Shang-Xun ZHOU ; Yi-Xuan DUAN ; Yu-Ying LI ; Yi LI ; Ya-Ling HAN
Journal of Geriatric Cardiology 2025;22(7):668-677
BACKGROUND:
The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.
METHODS:
A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed.
RESULTS:
During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.
CONCLUSIONS
SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.
3.Effect of PU.1 inhibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism
Nuo XU ; Ting-ting GUO ; Ying LI ; Kang WANG ; Wei WEI ; Shang-xue YAN
Chinese Pharmacological Bulletin 2025;41(8):1478-1484
Aim To investigate the effect of PU.1 in-hibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism.Methods Thirty female MRL/lpr mice were randomly divided into the model group,DB2313 group and TACI-Ig group,with 10 mice in each group.Another 10 female BALB/c mice were se-lected as normal control groups.Mice in the DB2313 group received intraperitoneal DB2313 injections every two days,and those in the TACI-Ig group received subcutaneous injections of TACI-Ig every two days.Mice in the control group and model group were intra-gastrically given the same amount of 0.9%NaCl injec-tion every day.Before the drug intervention and for 1 to 5 weeks after the intervention,the urine of mice was collected regularly,the urine protein content was meas-ured,and the renal damage index was evaluated.The histopathological changes of kidney were observed by HE,Masson and PAS staining.The expression levels of immune complex of C3 in kidney tissue were detec-ted by immunohistochemistry.The concentrations of u-rea nitrogen(BUN),serum creatinine(Scr),inter-leukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)in the serum samples were assayed utilizing the respective kits.The expression levels of PU.1 and FLT3 in kidney tissues were determined by immunoflu-orescence technology,and the protein expressions of PU.1,FLT3,PI3K,AKT and phosphorylated AKT(p-AKT)in kidney tissues were detected by Western blot.Results DB2313 treatment significantly allevia-ted the pathological damage of kidney in MRL/lpr mice,and reduced the deposition of C3,kidney injury index and 24-hour urine protein in renal tissue.The results of ELISA showed that DB2313 administration could significantly reduce the serum levels of BUN,Scr,IL-6 and TNF-α in MRL/lpr mice.The results of immunofluorescence and Western blot further showed that DB2313 treatment could significantly down-regu-late the protein expression of PU.1,PI3K and p-AKT,and up-regulate the protein expression of FLT3.Con-clusion DB2313 has an ameliorating effect on lupus nephritis in MRL/lpr mice,and its underlying mecha-nism may involve the inhibition of the transcription fac-tor PU.1-mediated signaling pathway.
4.Effect of acupuncture pretreatment on nerve cell ferroptosis in ischemic stroke
Ying GAO ; Jian YANG ; Jiangwei SHI ; Jing XUE ; Xiaoyu SHANG ; Hongtao DUAN ; Hairong WANG
Chinese Journal of Arteriosclerosis 2025;33(1):24-29
Aim To study the regulatory effect of acupuncture pretreatment on ferroptosis of nerve cells in rats with ischemic stroke.Methods Sixty SD rats were randomly divided into sham middle cerebral artery occlusion(MCAO)group,MCAO group,and acupuncture+MCAO group.In the acupuncture+MCAO group,the acupuncture points of DU26,PC6,and SP6,were selected for acupuncture pretreatment,once a day for a total of 5 days.After pre-treatment,MCAO or sham MCAO models were prepared.The Zausinger sextintegral method was used to score the neuro-logical function of rats,and the infarct volume of brain tissue was calculated by TTC staining.Electron microscopy was used to observe the pathomorphological changes of brain tissue.The iron content was detected by colorimetric method,the content of malondialdehyde(MDA)and glutathione(GSH)was determined by ELISA,and the expression of glutathione peroxidase 4(GPX4)was detected by immunofluorescence.Results Compared with the sham MCAO group,the MCAO group had a decrease in neurological function scores,a significant increase in infarct volume,a decrease in the number of mitochondria under electron microscopy,a rupture and vacuolization of the inner mitochondrial cristae,an in-crease in the contents of iron and MDA in brain tissue,and a decrease in GSH content and GPX4 expression.Compared with the MCAO group,the acupuncture+MCAO group had an increase in neurological function scores,a decrease in infarct volume,a large number of mitochondria under electron microscopy,a clear structure,a decrease or disordered arrangement of some mitochondrial crest structures,a decrease in the contents of iron and MDA in brain tissue,and an increase in GSH content and GPX4 expression.Conclusion Acupuncture pretreatment can alleviate neurological damage in rats,and its mechanism may be related to regulating iron,GSH and MDA contents in brain tissue,and GPX4 expression,improving cell antioxidant capacity and inhibiting nerve cell ferroptosis.
5.Overexpression of KAT7 promotes pyroptosis of chondrocytes
Ying LI ; Kang WANG ; Tian-xi DU ; Ting-ting GUO ; Nuo XU ; Xu-lei WANG ; Yan CHANG ; Wei WEI ; Shang-xue YAN
Chinese Pharmacological Bulletin 2025;41(7):1298-1305
Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.
6.A qualitative study on digital-intelligent equipment empowering"generalized"development of traditional Chinese medicine inspection
Chen ZHAO ; Aomeng ZHANG ; Zehui YE ; Jiaying LUO ; Qiang SHI ; Ying YU ; Xiaoyu ZHANG ; Yin JIANG ; Zhicong ZENG ; Fengxia LIN ; Yinghui JIN ; Xue XU ; Xiaowei ZHANG ; Liangzhen YOU ; Yipin FAN ; Dameng YU ; Shaoyang MEN ; Jian DU ; Rui XU ; Ruijin QIU ; Yingjie ZHI ; Zhineng CHEN ; Xuan ZHANG ; Hongcai SHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1052-1061
Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.
7.Effect of PU.1 inhibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism
Nuo XU ; Ting-ting GUO ; Ying LI ; Kang WANG ; Wei WEI ; Shang-xue YAN
Chinese Pharmacological Bulletin 2025;41(8):1478-1484
Aim To investigate the effect of PU.1 in-hibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism.Methods Thirty female MRL/lpr mice were randomly divided into the model group,DB2313 group and TACI-Ig group,with 10 mice in each group.Another 10 female BALB/c mice were se-lected as normal control groups.Mice in the DB2313 group received intraperitoneal DB2313 injections every two days,and those in the TACI-Ig group received subcutaneous injections of TACI-Ig every two days.Mice in the control group and model group were intra-gastrically given the same amount of 0.9%NaCl injec-tion every day.Before the drug intervention and for 1 to 5 weeks after the intervention,the urine of mice was collected regularly,the urine protein content was meas-ured,and the renal damage index was evaluated.The histopathological changes of kidney were observed by HE,Masson and PAS staining.The expression levels of immune complex of C3 in kidney tissue were detec-ted by immunohistochemistry.The concentrations of u-rea nitrogen(BUN),serum creatinine(Scr),inter-leukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)in the serum samples were assayed utilizing the respective kits.The expression levels of PU.1 and FLT3 in kidney tissues were determined by immunoflu-orescence technology,and the protein expressions of PU.1,FLT3,PI3K,AKT and phosphorylated AKT(p-AKT)in kidney tissues were detected by Western blot.Results DB2313 treatment significantly allevia-ted the pathological damage of kidney in MRL/lpr mice,and reduced the deposition of C3,kidney injury index and 24-hour urine protein in renal tissue.The results of ELISA showed that DB2313 administration could significantly reduce the serum levels of BUN,Scr,IL-6 and TNF-α in MRL/lpr mice.The results of immunofluorescence and Western blot further showed that DB2313 treatment could significantly down-regu-late the protein expression of PU.1,PI3K and p-AKT,and up-regulate the protein expression of FLT3.Con-clusion DB2313 has an ameliorating effect on lupus nephritis in MRL/lpr mice,and its underlying mecha-nism may involve the inhibition of the transcription fac-tor PU.1-mediated signaling pathway.
8.A qualitative study on digital-intelligent equipment empowering"generalized"development of traditional Chinese medicine inspection
Chen ZHAO ; Aomeng ZHANG ; Zehui YE ; Jiaying LUO ; Qiang SHI ; Ying YU ; Xiaoyu ZHANG ; Yin JIANG ; Zhicong ZENG ; Fengxia LIN ; Yinghui JIN ; Xue XU ; Xiaowei ZHANG ; Liangzhen YOU ; Yipin FAN ; Dameng YU ; Shaoyang MEN ; Jian DU ; Rui XU ; Ruijin QIU ; Yingjie ZHI ; Zhineng CHEN ; Xuan ZHANG ; Hongcai SHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1052-1061
Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.
9.Effect of acupuncture pretreatment on nerve cell ferroptosis in ischemic stroke
Ying GAO ; Jian YANG ; Jiangwei SHI ; Jing XUE ; Xiaoyu SHANG ; Hongtao DUAN ; Hairong WANG
Chinese Journal of Arteriosclerosis 2025;33(1):24-29
Aim To study the regulatory effect of acupuncture pretreatment on ferroptosis of nerve cells in rats with ischemic stroke.Methods Sixty SD rats were randomly divided into sham middle cerebral artery occlusion(MCAO)group,MCAO group,and acupuncture+MCAO group.In the acupuncture+MCAO group,the acupuncture points of DU26,PC6,and SP6,were selected for acupuncture pretreatment,once a day for a total of 5 days.After pre-treatment,MCAO or sham MCAO models were prepared.The Zausinger sextintegral method was used to score the neuro-logical function of rats,and the infarct volume of brain tissue was calculated by TTC staining.Electron microscopy was used to observe the pathomorphological changes of brain tissue.The iron content was detected by colorimetric method,the content of malondialdehyde(MDA)and glutathione(GSH)was determined by ELISA,and the expression of glutathione peroxidase 4(GPX4)was detected by immunofluorescence.Results Compared with the sham MCAO group,the MCAO group had a decrease in neurological function scores,a significant increase in infarct volume,a decrease in the number of mitochondria under electron microscopy,a rupture and vacuolization of the inner mitochondrial cristae,an in-crease in the contents of iron and MDA in brain tissue,and a decrease in GSH content and GPX4 expression.Compared with the MCAO group,the acupuncture+MCAO group had an increase in neurological function scores,a decrease in infarct volume,a large number of mitochondria under electron microscopy,a clear structure,a decrease or disordered arrangement of some mitochondrial crest structures,a decrease in the contents of iron and MDA in brain tissue,and an increase in GSH content and GPX4 expression.Conclusion Acupuncture pretreatment can alleviate neurological damage in rats,and its mechanism may be related to regulating iron,GSH and MDA contents in brain tissue,and GPX4 expression,improving cell antioxidant capacity and inhibiting nerve cell ferroptosis.
10.Overexpression of KAT7 promotes pyroptosis of chondrocytes
Ying LI ; Kang WANG ; Tian-xi DU ; Ting-ting GUO ; Nuo XU ; Xu-lei WANG ; Yan CHANG ; Wei WEI ; Shang-xue YAN
Chinese Pharmacological Bulletin 2025;41(7):1298-1305
Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

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