1.Effects of Aqueous Extract of Corn Silk Combined with Training on Exercise Function and Glycolipid Metabolism in Mice with Metabolic Syndrome
Yi-lin LIU ; Zi-ling SONG ; Ting ZHOU ; Ji-ping CHEN ; Zi-han LIN ; Yu-xuan ZHANG ; Ji-qiang ZENG ; Shan-rong ZHANG ; Zhi-peng WU ; Chen LU ; Ying ZHU
Progress in Modern Biomedicine 2025;25(15):2411-2420
Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P<0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P<0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P<0.05),while no significant difference was found between the CS+MT and CS+HT groups(P>0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P<0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P<0.05),with the CS+MT group having the lowest body weight(P<0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P<0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P<0.05),with the CS+MT and CS+HT groups showing the lowest levels(P<0.05).No significant difference was found between the CS+MT and CS+HT groups(P>0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P<0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P<0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P<0.05),with the CS+MT group showing the lowest AUC for OGTT(P<0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P<0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P<0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P<0.05),with no significant differences in TC and LDL-C levels between these two groups(P>0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.
2.Functional mechanism of Qushi Huoxue decoction in treating non-alcoholic fatty liver disease based on network pharmacology and experimental validation
Wei-qiang TAN ; Xiao-ke RAN ; Zhao-quan PAN ; Xu-dong LIU ; Ye-huang WEI ; Xiao-qian GONG ; Rong-rong WANG
Chinese Pharmacological Bulletin 2025;41(9):1761-1768
Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.
3.Influence of Acupuncture for Regulating the Mind and Replenishing Qi Combined with Butylphthalide Soft Capsules on Sleep Parameters and Neurological Function in Patients with Sleep Disorders after Stroke
Tan ZHANG ; Fang-yue ZENG ; Chen-rong HUANG ; Jia-yi ZHU ; Qiang ZHANG
Progress in Modern Biomedicine 2025;25(20):3238-3246
Objective:To observe the influence of acupuncture for regulating the mind and replenishing qi combined with butylphthalide soft capsules on sleep parameters and neurological function in patients with sleep disorders after stroke.Methods:From May 2022 to September 2024,a total of 85 patients with sleep disorders after stroke who were admitted to our hospital were prospectively included,and they were divided into control group(received treatment with butylphthalein soft capsules,42 cases)and study group(received treatment with acupuncture for regulating the mind and replenishing qi combined with butylphthalide soft capsules,43 cases)by the double chromosphere method.Sleep parameters,sleep quality score[pittsburgh sleep quality index(PSQI),insomnia severity index(ISI)],related functional scale score[modified edinburgh scandinavian stroke scale(MMSSS),hospital anxiety and depression scale(HADS),Fugl-Meyer assessment scale(FMA),montreal cognitive assessment(MoCA)]and related serum indicators[hypersensitive C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),5-hydroxy tryptamine(5-HT),gama-aminobutyric acid(GABA)]were compared between the two groups.Result:The total sleep time,sleep efficiency,FMA score,MoCA score,5-HT and GABA indicators in the study group after treatment were higher than those in the control group,the number of awakenings,sleep latency,PSQI score,ISI score,MESSS score,HADS score,hs-CRP and TNF-α indicators were lower than those in the control group(P<0.05).Conclusion:Acupuncture for regulating the mind and replenishing qi combined with butylphthalide soft capsules can effectively improve the sleep quality of patients with sleep disorders after stroke,regulate the neurological functions,reduce inflammatory factors levels,and improve the motor and cognitive function.
4.Functional mechanism of Qushi Huoxue decoction in treating non-alcoholic fatty liver disease based on network pharmacology and experimental validation
Wei-qiang TAN ; Xiao-ke RAN ; Zhao-quan PAN ; Xu-dong LIU ; Ye-huang WEI ; Xiao-qian GONG ; Rong-rong WANG
Chinese Pharmacological Bulletin 2025;41(9):1761-1768
Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.
5.Influence of Acupuncture for Regulating the Mind and Replenishing Qi Combined with Butylphthalide Soft Capsules on Sleep Parameters and Neurological Function in Patients with Sleep Disorders after Stroke
Tan ZHANG ; Fang-yue ZENG ; Chen-rong HUANG ; Jia-yi ZHU ; Qiang ZHANG
Progress in Modern Biomedicine 2025;25(20):3238-3246
Objective:To observe the influence of acupuncture for regulating the mind and replenishing qi combined with butylphthalide soft capsules on sleep parameters and neurological function in patients with sleep disorders after stroke.Methods:From May 2022 to September 2024,a total of 85 patients with sleep disorders after stroke who were admitted to our hospital were prospectively included,and they were divided into control group(received treatment with butylphthalein soft capsules,42 cases)and study group(received treatment with acupuncture for regulating the mind and replenishing qi combined with butylphthalide soft capsules,43 cases)by the double chromosphere method.Sleep parameters,sleep quality score[pittsburgh sleep quality index(PSQI),insomnia severity index(ISI)],related functional scale score[modified edinburgh scandinavian stroke scale(MMSSS),hospital anxiety and depression scale(HADS),Fugl-Meyer assessment scale(FMA),montreal cognitive assessment(MoCA)]and related serum indicators[hypersensitive C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),5-hydroxy tryptamine(5-HT),gama-aminobutyric acid(GABA)]were compared between the two groups.Result:The total sleep time,sleep efficiency,FMA score,MoCA score,5-HT and GABA indicators in the study group after treatment were higher than those in the control group,the number of awakenings,sleep latency,PSQI score,ISI score,MESSS score,HADS score,hs-CRP and TNF-α indicators were lower than those in the control group(P<0.05).Conclusion:Acupuncture for regulating the mind and replenishing qi combined with butylphthalide soft capsules can effectively improve the sleep quality of patients with sleep disorders after stroke,regulate the neurological functions,reduce inflammatory factors levels,and improve the motor and cognitive function.
6.Effects of Aqueous Extract of Corn Silk Combined with Training on Exercise Function and Glycolipid Metabolism in Mice with Metabolic Syndrome
Yi-lin LIU ; Zi-ling SONG ; Ting ZHOU ; Ji-ping CHEN ; Zi-han LIN ; Yu-xuan ZHANG ; Ji-qiang ZENG ; Shan-rong ZHANG ; Zhi-peng WU ; Chen LU ; Ying ZHU
Progress in Modern Biomedicine 2025;25(15):2411-2420
Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P<0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P<0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P<0.05),while no significant difference was found between the CS+MT and CS+HT groups(P>0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P<0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P<0.05),with the CS+MT group having the lowest body weight(P<0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P<0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P<0.05),with the CS+MT and CS+HT groups showing the lowest levels(P<0.05).No significant difference was found between the CS+MT and CS+HT groups(P>0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P<0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P<0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P<0.05),with the CS+MT group showing the lowest AUC for OGTT(P<0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P<0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P<0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P<0.05),with no significant differences in TC and LDL-C levels between these two groups(P>0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.
7.Analysis of NF1 Gene Variations in 10 Suspected Cases of Neurofibromatosis Type I and Families
Xin LI ; Lin WANG ; Rong QIANG ; Ruixue ZHANG ; Wenjing CHENG ; Yuanyuan CAO
Journal of Modern Laboratory Medicine 2025;40(3):169-172
Objective To study NF1 gene variations in 10 suspected cases of neurofibromatosis type I(NF1)and their parents,thereby providing a basis for genetic counselling,clinical diagnosis,and treatment of this disease.Methods A total of 10 patients diagnosed with,or suspected of having NF1 at Northwest Women's and Children's Hospital from March to December 2023 were selected as study subjects.Whole exome sequencing(WES)was performed to analyse NF1 gene mutations in the patients and their parents,with the findings validated by Sanger sequencing.Results Pathogenic mutations were identified in 6 of the 10 families,with the remaining 4 cases showing no pathogenic gene mutations.In Family 1,a de novo mutation,c.6505A>T,was detected in the NF1 gene.In Family 2,a de novo mutation,c.6705-3C>A,was identified in the NF1 gene.In Family 3,a de novo mutation,c.6853delT,was detected in the NF1 gene.In Family 4,a de novo mutation,c.2446C>T,was found in the NF1 gene.In Family 5,a paternal mutation,c.6067T>A,was identified in the NF1 gene.In Family 6,a paternal mutation,c.2991_2993dup,was detected in the NF1 gene.Conclusion The identification of new mutation sites enriches the mutation spectrum of the NF1 gene.This study provides important guidance for genetic counselling and prenatal diagnosis,offering crucial information for families with reproductive needs.
8.Nomogram based on clinical and DCE-MRI characteristics for predicting the depth of myometrial invasion and grade of endometrioid endometrial carcinoma
Xiaoliang MA ; Songqi CAI ; Jinwei QIANG ; Guofu ZHANG ; Jianjun ZHOU ; Mengsu ZENG ; Xiaojun REN ; Rong JIANG ; Minhua SHEN
Chinese Journal of Obstetrics and Gynecology 2025;60(3):202-215
Objective:To investigate the feasibility and value of nomogram based on base line clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) characteristics for pretreatment predicting the depth of myometrial invasion and tumor grade of endometrioid endometrial carcinoma (EEC).Methods:Preoperative baseline clinical characteristics and DCE-MRI characteristics of 194 EEC patients were prospectively collected at Obstetrics and Gynecology Hospital, Fudan University from October 2020 to January 2022 and used as a training set. Univariate analysis was conducted to compare baseline clinical characteristics and DCE-MRI quantitative parameters [including tumor volume, and mean, median, and standard deviation of volume transfer constant (K trans), rate constant (K ep), extravascular extracellular volume fraction (V e), and initial area under the enhancement curve (iAUC)] between patients with deep myometrial invasion (DMI) and those with superficial myometrial invasion (SMI), as well as between high-grade and low-grade EEC. Multivariate logistics regression analysis was used to identify independent predictors for the construction of nomogram. An independent external testing set comprising 127 EEC patients was retrospectively collected from Zhongshan Hospital, Fudan University and Zhongshan Hospital, Fudan University (Xiamen Branch). The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used for evaluating the model′s predictive performance and clinical net benefit, respectively. Results:(1) The depth of myometrial invasion: univariate analysis showed that in the training set, the EEC patients with DMI differed significantly from those with SMI in clinical characteristics including higher proportion of postmenopausal state and overweight [body mass index (BMI)≥25 kg/m2], and abnormal levels of serum cancer antigen (CA) 125, CA 199, and human epididymis protein 4 (HE4), and in DCE-MRI quantitative parameters including tumor volume, and median, mean, and standard deviation of K trans, median of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, CA 199, tumor volume, and mean of iAUC were independent predictors of the depth of myometrial invasion, and constructed the nomogram (recorded as Nomogram_1), achieving an AUC of 0.861 (95% CI: 0.803-0.919) in the training set. In the independent external testing set, the AUC was 0.876 (95% CI: 0.815-0.938), with corresponding sensitivity of 82.0%, specificity of 80.7%, accuracy of 81.1%, positive predictive value (PPV) of 65.3%, and negative predictive value (NPV) of 91.0% for predicting DMI. (2) The EEC grade: univariate analysis showed that in the training set, high-grade EEC patients differed significantly from low-grade EEC in clinical characteristics including patient′s age, the proportion of postmenopausal state and overweight, and abnormal levels of serum CA 125, and in DCE-MRI quantitative parameters including tumor volume, median, mean, and standard deviation of K trans, median and mean of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, tumor volume, and median of V e emerged as independent predictors of EEC grade, and constructed the nomogram (recorded as Nomogram_2), achieving an AUC of 0.845 (95% CI: 0.786-0.893) in the training set. While in the external testing set, the AUC was 0.819 (95% CI: 0.744-0.894), with corresponding sensitivity of 72.4%, specificity of 72.4%, accuracy of 72.4%, PPV of 43.8%, and NPV of 89.9% for predicting high-grade EEC. (3) The DCA curves demonstrated that both Nomogram_1 and Nomogram_2 yielded obvious positive clinical net benefits across a wide range of threshold probabilities. Conclusion:The nomogram based on pretreatment clinical and DCE-MRI characteristics has the potential to noninvasive predict the depth of myometrial invasion and grade of EEC, providing valuable reference information for clinical management decision-making.
9.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
10.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.

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