1.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
2.Protective effect of achyranthes bidentata against doxorubicin-induced spermatogenic disorder in mice:An investigation based on the glycolytic metabolic pathway
Man-yu WANG ; Yang FU ; Pei-pei YUAN ; Li-rui ZHAO ; Yan ZHANG ; Qing-yun MA ; Yan-jun SUN ; Wei-sheng FENG ; Xiao-ke ZHENG
National Journal of Andrology 2025;31(2):99-107
Objective:To investigate the protective effect of achyranthes bidentata(AB)on sperm quality in mice with sper-matogenic disorder through the glycolytic metabolic pathway and its action mechanism.Methods:We equally randomized 40 Kun-ming mice into a normal control,a model control,a low-dose AB(3.5 g/kg)and a high-dose AB group(7.0 g/kg),and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin(30 mg/kg).Two days after modeling,we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining,detection of perm motility with the sperm quality analyzer,examination of the apoptosis of testis cells by flow cytometry,measurement of the levels of testosterone(T),malondialdehyde(MDA),superoxide dismutase(SOD)and cata-lase(CAT)in the serum and testis tissue by ELISA,and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ(HK2),pyruvate kinase M2(PKM2),platelet phosphofructokinase(PFKP),lactate dehydrogenase A(LDHA)and the meiosis pro-teins REC8 and SCP3 by Western blot,and the mRNA expressions of glycolytic phosphofructokinase 1(PFK1),phosphoglycerate ki-nase 1(PGK1),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)by fluorescence quantitative PCR(FQ-PCR).Results:Compared with the model controls,the mice in the AB groups showed significant increases in the testis coefficient,kidney in-dex,sperm concentration,sperm motility,spermatogonia,primary spermatocytes,spermatids,sperm count and the serum T level(P<0.05 orP<0.01),but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm(P<0.01).Achyranthes bidentata also significantly elevated the levels of SOD and CAT,and down-regulated the mRNA expressions of MDA,TNF-α and IL-1β(P<0.05 or P<0.01),and up-regulated the protein expressions of HK2,PKM2,PFKP,LDHA,REC8 and SCP3,and expressions of the glycolysis key genes Pfk1 and Pgk1(P<0.05 orP<0.01).Conclusion:Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.
3.Research on the Standardization System of Mineral Medicines
Chunmei LIU ; Yuan SUN ; Min ZHANG ; Shaowu SHEN ; Guohua ZHENG ; Bisheng HUANG ; Juan LI
Herald of Medicine 2025;44(10):1709-1716
Objective On the basis of systematically summarizing and organizing the existing standards of mineral drugs in traditional Chinese medicine,this study aims to construct the top-level framework of the mineral drug standard system and promote the standardization process of the mineral drug industry.Methods A comprehensive search and analysis of the standards for 87 kinds of mineral drugs were conducted on authoritative platforms such as the National Standard Information Public Service Platform,China Standard Service Network,and Traditional Chinese Medicine Standard and Guideline Information Service.By delving into the theoretical foundation and scientific methods,combined with practical research,this study uses analogy reference,systematic decomposition,and process analysis to design the top-level framework of the mineral drug standard system.Results Through comprehensive analysis and scientific design,this study summarizes the construction process and methods of the mineral drug standard system,clarifies the hierarchical structure and classification principles of the system,proposes the compilation path,and forms a standard system covering the entire industry chain of mineral drugs,including raw minerals,product categories,and circulation categories.Conclusion This study constructs a full industry chain process framework for the standard system of mineral drugs,providing a clear perspective for the research of mineral drugs.It can more comprehensively display the current state of development of mineral drug standards in our country,laying a foundation for the research on the standardization of mineral drugs.
4.Ultrasound radiomics combined with machine learning for early diagnosis of seronegative hashimoto’s thyroiditis
Wenjun WU ; Chang LIU ; Shengsheng YAO ; Daming LIU ; Yuan LUO ; Yihan SUN ; Ting RUAN ; Mengyou LIU ; Li SHI ; Mingming XIAO ; Qi ZHANG ; Zhengshuai LIU ; Xingai JU ; Jiahao WANG ; Xiang FEI ; Li LU ; Yang GAO ; Ying ZHANG ; Liying GONG ; Xuanyu CHEN ; Wanli ZHENG ; Xiali NIU ; Xiao YANG ; Huimei CAO ; Shijie CHANG ; Zuoxin MA ; Jianchun CUI
Chinese Journal of Endocrine Surgery 2025;19(3):313-319
Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.
5.Predictive value of dual-energy CT quantitative parameters in determining breast cancer molecular subtypes and EGFR expression
Bing SUN ; Yinshi ZHENG ; Kunpeng FENG ; Mu YUAN ; Hongmei CHEN ; Wenqi HUANG
Chinese Journal of Endocrine Surgery 2025;19(2):213-217
Objective:To explore the predictive potential of dual-energy CT (DECT) quantitative parameters in identifying breast cancer molecular subtypes and the expression of the epidermal growth factor receptor (EGFR) .Methods:A cohort of 97 breast cancer patients, treated between Jun. 2022 and Jun. 2024 were selected. The study compared DECT parameters-such as iodine concentration (IC) , normalized iodine concentration (NIC) , spectral curve slope (λ HU) , and effective atomic number (Z eff) in both arterial and venous phases across different molecular subtypes. A multiclass logistic regression model was employed to assess the parameters' value in predicting molecular subtypes, while a binary logistic regression model was used to evaluate their predictive value for EGFR expression. Results:Multiple Logistic regression analysis showed that after adjusting for confounder age and family history, IC ( OR=1.72, 2.78, 3.05) , NIC ( OR=2.52, 1.94, 2.93) , λ HU ( OR=2.08, 2.54, 3.17) and Z eff ( OR=2.03, 2.30, 2.37) at arterial stage were independently correlated with the molecular subtypes of breast cancer ( P<0.05) . Binary logistic regression analysis, adjusted for tumor size and lymph node metastasis, identified arterial phase IC ( OR=3.45) , NIC ( OR=2.73) , λ HU ( OR=2.59) , and Z eff ( OR=1.76) as independent risk factors for EGFR-positive breast cancer ( P<0.05) . Conclusion:DECT quantitative parameters, particularly arterial phase IC, NIC, λ HU, and Zeff, offer valuable insights into the molecular subtyping of breast cancer and EGFR expression, thereby assisting in the development of personalized treatment strategies.
6.Value of dual-energy CT quantitative measurement of lumbar spine combined with serum BALP,BGP, β-CTx in predicting osteoporotic fractures
Bing SUN ; Yinshi ZHENG ; Yiming LI ; Yuan SUI ; Xinglong WANG ; Wenqi HUANG
Chinese Journal of Endocrine Surgery 2025;19(5):740-744
Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.
7.Clinical efficacy of Di'ao Xinxuekang Capsules combined with injectable pancreatic kallidinogenase in the treatment of diabetic retinopathy
Zheng SUN ; Xiaoye WANG ; Jing YUAN ; Binhong WEN
Chinese Journal of Primary Medicine and Pharmacy 2025;32(10):1477-1481
Objective:To investigate the clinical efficacy of Di'ao Xinxuekang Capsules combined with injectable pancreatic kallidinogenase in the treatment of diabetic retinopathy. Methods:This study was a prospective research. A total of 90 patients with diabetic retinopathy treated at The People's Hospital of Liaoning Province from September 2021 to March 2024 were included in this study. The patients were randomly assigned to an observation group and a control group, with 45 patients in each group, using the random number table method. The control group received treatment with injectable pancreatic kallidinogenase, while the observation group underwent treatment with Di'ao Xinxuekang Capsules in addition to injectable pancreatic kallidinogenase. Both groups were treated for 14 days. The clinical efficacy, changes in visual acuity after treatment compared with before treatment, ocular hemodynamic indicators (peak systolic velocity and resistance index), and the incidence of adverse reactions were compared between the two groups. Results:The response rate in the observation group was significantly higher than that in the control group [90.91% (40/45) vs. 73.33% (33/45), χ2 = 8.61, P<0.05]. Before treatment, there were no significant differences between the two groups regarding visual acuity values, retinal thickness, and ocular hemodynamic parameters ( t = 0.11, 0.05, 0.47, 1.08, all P>0.05). After 14 days of treatment, the visual acuity in the observation group was significantly higher than that in the control group [(1.06 ± 0.11) vs. (0.81 ± 0.06), t = 12.62, P<0.001]. The peak systolic velocity in the observation group was significantly greater than that in the control group [(31.85 ± 1.92) cm/s vs. (27.01 ± 1.33) cm/s, t = 8.01, P<0.001]. The retinal thickness in the observation group was significantly lower than that in the control group [(311.5 ± 45.2) μm vs. (350.3 ± 59.3) μm, t = -3.49, P<0.001]. The resistance index in the observation group was significantly lower than that in the control group [(0.59 ± 0.02) vs. (0.68 ± 0.04), t = -12.57, P<0.001]. There was no significant difference in the incidence of adverse reactions between the observation and control groups [8.89% (4/45) vs. 6.67% (3/45), χ2 = 0.16, P>0.05]. Conclusions:Di'ao Xinxuekang Capsules combined with injectable pancreatic kallidinogenase for the treatment of diabetic retinopathy can effectively enhance clinical efficacy, improve patients' visual acuity and ocular hemodynamic indicators, and is considered safe.
8.Clinical study on the treatment of type 2 diabetes mellitus complicated by metabolic-associated fatty liver disease using Zhibitai capsules combined with liraglutide
Zheng SUN ; Jing YUAN ; Xiaoye WANG ; Binhong WEN
Chinese Journal of Primary Medicine and Pharmacy 2025;32(11):1667-1672
Objective:To investigate the clinical efficacy of Zhibitai capsules combined with liraglutide in the treatment of type 2 diabetes mellitus (T2MD) complicated by metabolic-associated fatty liver disease (MAFLD). Methods:This study used a prospective design. A total of 92 patients with T2DM complicated by MAFLD who were admitted to The People's Hospital of Liaoning Province from September 2023 to September 2024 were included in this study. They were randomly divided into an observation group and a control group, with 46 patients in each group. Both groups received lifestyle intervention and standard antidiabetic treatment. The control group received subcutaneous injections of liraglutide, while the observation group was treated with liraglutide combined with Zhibitai capsules. All patients were treated for 3 months. Blood glucose levels, glycated hemoglobin, blood lipid levels, liver function, and hemodynamic parameters were compared between the two groups both before and after treatment. The controlled attenuation parameter of liver fat was measured using Fibro Touch. Results:After treatment, there were no statistically significant differences in fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin levels between the two groups (all P > 0.05). The high-density lipoprotein cholesterol level in the observation group was significantly higher than that in the control group [(1.31 ± 0.40) mmol/L vs. (0.90 ± 0.30) mmol/L, t = -5.56, P < 0.001]. The levels of total cholesterol [(3.70 ± 0.80) mmol/L vs. (4.40 ± 0.90) mmol/L], triglycerides [(1.50 ± 0.40) mmol/L vs. (2.60 ± 0.50) mmol/L], and low-density lipoprotein cholesterol [(1.80 ± 0.50) mmol/L vs. (2.60 ± 0.60) mmol/L] in the observation group were significantly lower than those in the control group ( t = 3.94, 11.65, 6.39, all P < 0.001). The controlled attenuation parameter of liver fat in the observation group was significantly lower than that in the control group [(249.20 ± 7.60) dB/m vs. (264.70 ± 8.70) dB/m, t = 9.10, P < 0.001]. The level of total bilirubin in the observation group was significantly higher than that in the control group [(16.40 ± 1.50) μmol/L vs. (15.00 ± 1.40) μmol/L, t = -4.63, P < 0.05], while the levels of other liver function indicators in the observation group were significantly lower than those in the control group ( t = 4.83, 9.57, 3.66, all P < 0.001). After treatment, whole blood viscosity at high shear rates, whole blood viscosity at lower shear rates, plasma viscosity, and platelet aggregation levels were all significantly lower in the observation group compared with the control group ( t = 2.13, 2.62, 2.97, 6.15, 4.00, all P < 0.05). Conclusions:Zhibitai capsules combined with liraglutide can improve blood glucose levels, lipid profiles, and liver function, while also decreasing blood viscosity in patients with T2MD complicated by MAFLD.
9.Ultrasound radiomics combined with machine learning for early diagnosis of seronegative hashimoto’s thyroiditis
Wenjun WU ; Chang LIU ; Shengsheng YAO ; Daming LIU ; Yuan LUO ; Yihan SUN ; Ting RUAN ; Mengyou LIU ; Li SHI ; Mingming XIAO ; Qi ZHANG ; Zhengshuai LIU ; Xingai JU ; Jiahao WANG ; Xiang FEI ; Li LU ; Yang GAO ; Ying ZHANG ; Liying GONG ; Xuanyu CHEN ; Wanli ZHENG ; Xiali NIU ; Xiao YANG ; Huimei CAO ; Shijie CHANG ; Zuoxin MA ; Jianchun CUI
Chinese Journal of Endocrine Surgery 2025;19(3):313-319
Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.
10.Predictive value of dual-energy CT quantitative parameters in determining breast cancer molecular subtypes and EGFR expression
Bing SUN ; Yinshi ZHENG ; Kunpeng FENG ; Mu YUAN ; Hongmei CHEN ; Wenqi HUANG
Chinese Journal of Endocrine Surgery 2025;19(2):213-217
Objective:To explore the predictive potential of dual-energy CT (DECT) quantitative parameters in identifying breast cancer molecular subtypes and the expression of the epidermal growth factor receptor (EGFR) .Methods:A cohort of 97 breast cancer patients, treated between Jun. 2022 and Jun. 2024 were selected. The study compared DECT parameters-such as iodine concentration (IC) , normalized iodine concentration (NIC) , spectral curve slope (λ HU) , and effective atomic number (Z eff) in both arterial and venous phases across different molecular subtypes. A multiclass logistic regression model was employed to assess the parameters' value in predicting molecular subtypes, while a binary logistic regression model was used to evaluate their predictive value for EGFR expression. Results:Multiple Logistic regression analysis showed that after adjusting for confounder age and family history, IC ( OR=1.72, 2.78, 3.05) , NIC ( OR=2.52, 1.94, 2.93) , λ HU ( OR=2.08, 2.54, 3.17) and Z eff ( OR=2.03, 2.30, 2.37) at arterial stage were independently correlated with the molecular subtypes of breast cancer ( P<0.05) . Binary logistic regression analysis, adjusted for tumor size and lymph node metastasis, identified arterial phase IC ( OR=3.45) , NIC ( OR=2.73) , λ HU ( OR=2.59) , and Z eff ( OR=1.76) as independent risk factors for EGFR-positive breast cancer ( P<0.05) . Conclusion:DECT quantitative parameters, particularly arterial phase IC, NIC, λ HU, and Zeff, offer valuable insights into the molecular subtyping of breast cancer and EGFR expression, thereby assisting in the development of personalized treatment strategies.

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