1.Comparison of Wild and Cultivated Gardeniae Fructus Based on Traditional Quality Evaluation
Yuanjun SHANG ; Bo GENG ; Xin CHEN ; Qi WANG ; Guohua ZHENG ; Chun LI ; Zhilai ZHAN ; Junjie HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):225-234
ObjectiveBased on traditional quality evaluation of Gardeniae Fructus(GF) recorded in historical materia medica, this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics, microscopic features, and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length, diameter and individual fruit weight of wild and cultivated GF, and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF, and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently, the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China, the starch content was measured by anthrone colorimetric method, the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method, the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection(HPLC-ELSD), and the contents of representative components in them were measured by ultra-performance liquid chromatography(UPLC). Finally, correlation analysis was conducted between quality traits and phenotypic traits, combined with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), key differential components between wild and cultivated GF were screened. ResultsIn terms of traits, the wild GF fruits were smaller, exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger, displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF, while the blue-yellow value(b*) of wild GF was significantly higher than that of cultivated GF. In the microstructure, the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals, while the endocarp contained stone cell class round, polygonal or tangential prolongation, undeveloped seeds were visible within the fruit. In contrast, the mesocarp of cultivated GF contained few calcium oxalate cluster crystals, or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like, with the innermost layer arranged in a grid pattern. Seeds were basically mature, and only a few immature seeds existed in some batches. Regarding primary metabolite content, wild GF exhibited significantly higher total polysaccharide level than cultivated GF(P<0.01). In category-specific component content, wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF(P<0.01). Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside and chlorogenic acid compared to cultivated GF(P<0.01). Conversely, the contents of genipin 1-gentiobioside, geniposide and genipin were significantly lower in wild GF(P<0.01). ConclusionThere are significant differences between wild and cultivated GF in terms of traits, microstructure, and contents of primary and secondary metabolites. At present, the quality evaluation system of cultivated GF remains incomplete, and this study provides a reference for guiding the production of high-quality GF medicinal materials.
2.Improvement effects and mechanism of water extract from Chrysanthemum morifolium on muscle atrophy in rats after ischemic stroke
Ruocong YANG ; Hu QI ; Yuanlin GAO ; Zeyang ZHANG ; Xiaorui CHEN ; Rong LIU ; Nan ZENG
China Pharmacy 2025;36(5):535-539
OBJECTIVE To study the improvement effects and potential mechanisms of water extract from Chrysanthemum morifolium on skeletal muscle atrophy in rats after ischemic stroke. METHODS Sprague-Dawley rats were randomly divided into sham operation group, model group, ATP group (10 mg/kg), C. morifolium water extract high-dose and low-dose groups (1.08, 0.54 g/kg). Except for sham operation group, ischemic stroke models were induced in rats from the other groups using middle cerebral artery occlusion. Starting from the first day after surgery, rats in each group were given corresponding drug/normal saline intragastrically, once a day, for consecutive 7 days. On the 7th day post-surgery, the rats’ body weights were measured, and their motor functions were evaluated, including Longa scores, exercise distance, grip strength; the electrophysiological signals of the skeletal muscles in rats were measured; the pathological morphology of the soleus muscle in rats was observed; the levels of tumor necrosis factor-α (TNF-α) in serum and soleus muscle were measured; the expressions of proteins related to TNF-α/c-Jun N- terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling pathway in the soleus muscle were determined. RESULTS Compared with sham operation group, the body weight, grip strength and exercise distance of rats were decreased/ shortened significantly (P<0.01); additionally, there was a notable reduction in the interpeak value of skeletal muscle electrophysiology (P<0.05 or P<0.01). Longa score, as well as the levels of TNF-α in serum and soleus muscle, and the expression levels of TNF-α, phosphorylated JNK, phosphorylated MAPK, muscle ring-finger protein-1, and muscle atrophy Fbox- 1 protein in the soleus muscle, were all significantly elevated (P<0.01). The skeletal muscle cells of the soleus muscle in the model group showed significant atrophy, with a markedly decreased cross-sectional area (P<0.01). Compared with the model group, the levels of the aforementioned indicators were significantly reversed in C. morifolium water extract groups (P<0.05 or P< 0.01), and the skeletal muscle cells of the soleus muscle were markedly enlarged. CONCLUSIONS C. morifolium water extract can improve skeletal muscle atrophy in rats after ischemic stroke, the mechanism of which may be associated with suppressing the activation of the TNF- α/JNK/MAPK E-mail:19932015@cdutcm.edu.cn signaling pathway.
3.Effect of oxymatrine on expression of stem markers and osteogenic differentiation of periodontal ligament stem cells
Jing LUO ; Min YONG ; Qi CHEN ; Changyi YANG ; Tian ZHAO ; Jing MA ; Donglan MEI ; Jinpeng HU ; Zhaojun YANG ; Yuran WANG ; Bo LIU
Chinese Journal of Tissue Engineering Research 2025;29(19):3992-3999
BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.
4.Effect of Huangqin Qingre Chubi Capsules-containing Serum on CircRNA_0001543/NF-κB Expression in Co-cultured PBMCs and Human FLSs from Patients with Ankylosing Spondylitis
Yajun QI ; Jian LIU ; Qiao ZHOU ; Yuedi HU ; Xiang DING ; Chengzhi CONG ; Xu LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):87-95
ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B (NF-κB) in co-cultured peripheral blood mononuclear cells (PBMCs) and human fibroblast-like synoviocytes (FLSs) from patients with ankylosing spondylitis (AS). MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs, and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs, while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells(6.48 g·kg-1). To investigate the effect of HQC-containing serum on the viability of co-cultured cells, and the experiment was divided into the following groups based on the dilution concentration: blank group, 10% HQC group, 20% HQC group, and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group, the experiment was divided into three groups: normal group, model group, and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid, the experiment was divided into the following groups: blank group, si-NC group (with transfection reagent), si-circ_0001543-1 group (with transfection reagent and interference plasmid No. 1 targeting circ_0001543), si-circ_0001543-2 group (with transfection reagent and interference plasmid No. 2 targeting circ_0001543), and si-circ_0001543-3 group (with transfection reagent and interference plasmid No. 3 targeting circ_0001543).For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid, the experiment was divided into the following groups: blank group, OE-NC group (with transfection reagent), and OE-circ_0001543 group (with transfection reagent and overexpression plasmid targeting circ_0001543).To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group, the experiment was divided into the following groups: si-NC group, si-CircRNA_0001543 group, OE-NC group, and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin-1β (IL-1β), IL-10, IL-37, and tumor necrosis factor-α (TNF-α). Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to measure the expression of CircRNA_0001543, IκBα, and NF-κB p65. ResultsAfter 48 hours, 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs, which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the model group were significantly increased (P<0.01), while the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly decreased (P<0.01). Compared with those in the model group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased (P<0.05), and the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly increased (P<0.05), with the most prominent changes in the 30% drug-containing serum group (P<0.01). Compared with that in the si-NC group, the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group (P<0.01). Compared with that in the OE-NC group, the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group (P<0.01), indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules, si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α and decreased the expressions of IL-10 and IL-37 (P<0.01). In contrast, OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α (P<0.01) and increased the expressions of IL-10 and IL-37 (P<0.01). ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543, regulating the NF-κB pathway, suppressing pro-inflammatory cytokines, and enhancing anti-inflammatory cytokine expression.
5.Preliminary development with reliability and validity testing of health literacy assessment scale for junior high school students
QI Tiantian, ZHU Fan, ZHU Guiyin, GUO Shihao, YANG Shuang, WU Huiyun, HU Bin, JIANG He, MA Yinghua
Chinese Journal of School Health 2025;46(6):816-820
Objective:
To develop and validate a health literacy assessment scale for junior high school students, providing an effective tool for evaluating and monitoring health literacy among Chinese adolescents.
Methods:
Based on school health education policy documents, a health literacy assessment framework was constructed, comprising five horizontal and four vertical dimensions. From May to June and August to September in 2024, the framework was refined through Delphi expert consultations and focus group discussions, leading to the development of the Health Literacy Assessment Scale for Junior High School Students. In September 2024, a convenience sample of 625 students from three junior high schools in Beijing and Tianjin completed the questionnaire. Item analysis, reliability, and validity tests were conducted to evaluate the scale.
Results:
The recovery rate for two rounds of expert consultation questionnaires was 100%. The expert authority coefficients ( Cr ) were 0.86 and 0.87 respectively (both >0.70), with Kendall W values of 0.34 and 0.27 ( P <0.05). The focus group discussions followed a rigorous structure, and after multiple rounds of item screening and revision, the version 3.0 of the junior high school students health literacy assessment scale was developed, comprising 57 items. Three items that failed to meet the comprehensive screening criteria were preliminarily removed, and the final scale contained 54 items. The scale demonstrated excellent reliability, with an overall Cronbach s α coefficient of 0.92 and split half reliability of 0.93. Confirmatory factor analysis [ χ 2/df =2.094, root mean square error of approximation ( RMSEA )=0.042, comparative fit index ( CFI )=0.911, Tucker Lewis index ( TLI )=0.907] indicated good model fit indices.
Conclusions
The preliminary development of the health literacy assessment scale for junior high school students follows a rigorous item screening process with well designed dimensions, demonstrating good reliability and validity, thus serving as an appropriate evaluation tool for adolescent health literacy.
6.Evaluation progress of the application of staplers in thoracoscopic lung surgery
Shenghui LI ; Yijiu REN ; Hang SU ; Minglei YANG ; Guofang ZHAO ; Yongxiang SONG ; Xuefei HU ; Deping ZHAO ; Qi XUE ; Chang CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):709-713
Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.
7.Houshihei San Repairs Skeletal Muscle Injury After Ischaemic Stroke by Regulating Ferroptosis Pathway
Hu QI ; Dan TIAN ; Xiongwei ZHANG ; Zeyang ZHANG ; Yuanlin GAO ; Yanning JIANG ; Xinran MIN ; Jiamin ZOU ; Jiuseng ZENG ; Nan ZENG ; Ruocong YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):1-11
ObjectiveTo investigate the pharmacodynamic effects of Houshihei San (HSHS) recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion (MCAO) in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows: sham, MCAO, deferoxamine mesylate, high-dose HSHS (HSHS-H, 0.54 g·kg-1), and low-dose HSHS (HSHS-L, 0.27 g·kg-1), with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model, and rats were administrated with corresponding agents by gavage for 7 days. During the administration period, behavioral, imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently, immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 (GPX4) in the soleus tissue. Western blot was employed to determine the protein levels of p53, GPX4, myogenic differentiation 1 (MyoD1), nuclear factor E2-related factor 2 (Nrf2), Myostatin, solute carrier family 7 member 11 (SLC7A11), muscle ring-finger protein-1 (MuRF1), and muscle atrophy F-box protein (MAFbx) to verify the therapeutic effect in each group. ResultsCompared with the MCAO group, HSHS enhanced the locomotor ability and promoted muscle regeneration, which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group, HSHS ameliorated neurological impairments in rats on day 7 (P<0.01), enhanced 5-min locomotor distance and postural control (P<0.01), strengthened grasping power and promoted muscle growth (P<0.01), stabilized skeletal muscle length and weight (P<0.01), and increased the cross-section of muscle cells (P<0.01). Compared with the MCAO group, HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content (P<0.05,P<0.01). Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells (P<0.01). HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4, Nrf2, SLC7A11, and MyoD1 and inhibiting the expression of p53, Myostatin, MurRF1, and MAFbx to reduce ferroptosis in the muscle (P<0.01). ConclusionHSHS, prepared with reference to the method in the Synopsis of Golden Chamber, can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.
8.Analysis of incidence of stroke in Beilun District, Ningbo City, Zhejiang Province, 2012‒2023
Kunpeng GU ; Qi HU ; Qiaofang LI ; Zhiliang FAN ; Hang HONG
Shanghai Journal of Preventive Medicine 2025;37(7):586-590
ObjectiveTo analyze the incidence and trend of stroke in Beilun District, so as to provide evidence for identifying influencing factors and reducing stroke incidence. MethodsStroke cases from 2012 to 2023 were extracted from the Ningbo Chronic Disease Collaborative Management System. Population information of Beilun District during the same period was also collected. The annual incidence and trends of stroke were analyzed. ResultsFrom 2012 to 2023, the age-standardized incidence rate of stroke in Beilun District, Ningbo City was 317.68/100 000, showing an increasing trend with an average annual percentage change (AAPC) of 2.267% (P=0.034). Among all subdistricts in Beilun District, two showed a downward trend in incidence, while the rest showed an upward trend. The crude incidence rate of stroke was significantly higher in males than that in females (P<0.001). The age-standardized incidence rate in males was 406.08/100 000, showing an increasing trend (AAPC=3.956%, P<0.001). The incidence of stroke also showed an increasing trend in the following age groups: 30‒<45 years (AAPC=6.340%, P=0.004), 45‒<60 years (AAPC=4.997%, P<0.001), and 60‒<75 years (AAPC=3.282%, P=0.042). Across all years, males had higher crude incidence rates in both ischemic and hemorrhagic stroke than females (P<0.05). The age-standardized incidence rate of ischemic stroke showed a rising trend in both males and the general population (male AAPC=4.905%, P<0.001; overall population AAPC=3.065%, P=0.001). ConclusionThe age-standardized incidence of stroke in Beilun District is on the rise, with higher crude incidence rate in males than that in females. The onset age of stroke is gradually declining. The age-standardized incidence rate of male ischemic stroke shows a clear upward trend.
9.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
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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