1.Indole-3-aldehyde-loaded inulin-based hydrogel for protection against radiation-induced intestinal injury
Tuo LI ; Feifei MA ; Jiebing GUAN ; Siyu XIE ; Ning WANG ; Ningning HE ; Huijuan SONG ; Jianguo LI ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(5):408-415
Objective:To explore the protective effects and mechanisms of an indole-3-acetaldehyde (I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury.Methods:The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer, and its biocompatibility was assessed via a CCK-8 assay. Eighteen C57BL/6 mice (aged: 6-8 weeks) were stratified by body weight and randomly assigned into three groups with 6 mice in each group: blank control, irradiation-only, and irradiation+ hydrogel protection. Abdominal irradiation was administered using 137Cs γ-rays at 17 Gy. The irradiation+ hydrogel protection group received 200 μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation. Meanwhile, the irradiation-only group was treated with an equivalent volume of sterile water via gavage. The mice were euthanized four days post-irradiation, and their intestinal tissues were harvested. Hematoxylin-eosin (HE) staining, Ki67 immunohistochemistry, and TUNEL immunofluorescence were performed to assess histopathological damage, epithelial cell proliferation, and apoptosis, respectively. Quantitative real-time PCR (qRT-PCR) was employed to measure mRNA levels of inflammatory and antioxidant factors. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results:The test results of the rheometer confirmed successful hydrogel formation. CCK-8 assays demonstrated excellent biocompatibility. Compared with the irradiation-only group, the irradiation+ hydrogel protection group exhibited preserved intestinal histoarchitecture, a 1.5-fold increase in intestinal cell proliferation ( t = 8.35, P < 0.05), and a 2-fold reduction in radiation-induced apoptosis ( t = 7.94, P < 0.05). Moreover, the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1 ( t = 3.16, 24.83, 5.92, P < 0.05), alongside reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α ( t = 5.15, 3.82, 3.83, P < 0.05). Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group. Conclusions:The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation, reduce radiation-induced apoptosis, and enhance both anti-inflammatory and antioxidant responses. In addition, it regulates gut microbiota composition and abundance, protecting against radiation-induced intestinal injury.
2.Advances in the application of PET/CT molecular imaging probes to the treatment of breast cancer
Huayu LI ; Jiaying SONG ; Tao YE ; Yucong WANG ; Lianfu WANG ; Qiang LI
Chinese Journal of Radiological Medicine and Protection 2025;45(5):497-502
Breast cancer, a malignant tumor that significantly endangers women′s health, has shown a gradually rising incidence in recent years. Some breast cancer patients experienced poor prognosis. The commonly used imaging techniques for breast cancer include ultrasound, mammography, and magnetic resonance (MR), which suffer from certain limitations in accurately diagnosing and staging breast cancer. Positron emission tomography/computed tomography (PET/CT) enables tumor imaging at the cellular and molecular levels by utilizing radiolabeled molecular probes targeting different ligands. This technique facilitates precise localization and qualitative diagnosis of lesions to improve the staging accuracy, thereby reducing biopsy frequency and enhancing treatment effects for patients. Therefore, PET/CT has gradually developed into an essential imaging method for breast cancer in clinical practice. It plays a critical role in assessing the extent of lesion invasion, predicting immune subtypes, and estimating targeted therapy efficacy, holding promising application prospects. Recently, significant research breakthroughs have been achieved in this field. This review summarized the advances in clinical applications of different PET/CT molecular probes in the diagnosis and treatment of breast cancer, aiming to enhance the understanding of this aspect.
3.Influence of helical tomography radiotherapy planning parameters on threading effect
Ruo-qi CAO ; Xia-yu HANG ; Hua HUANG ; Xian-qiang SONG ; Jin-da ZHOU ; Yun-jie BAI ; Xiang-dong SUN ; Yi-kun LI
Chinese Medical Equipment Journal 2025;46(8):58-66
Objective To investigate the influence of helical tomographic radiotherapy plans with different combinations of lead gate width,pitch and algorithms on threading effects.Methods A target model was established with a Cheese Phantom used as the simulated human body,then three lead gate widths(1.0,2.5,and 5.0 cm),six screw pitches(0.143,0.172,0.215,0.287,0.430,and 0.500)and two computational grids(Fine algorithm and Normal algorithm)were respectively combined for designing the helical tomography radiotherapy plans.The radiotherapy plans with a pitch of 0.143,0.172,0.215,0.287 or 0.430 were enrolled into an experimental group,and the plans with a pitch of 0.500 were divided into a control group.The dosimetric parameters including maximum dose(Dmax),minimum dose(Dmin)and mean dose(Dmean)of the target area PTV1 and PTV2 were evaluated by the dose volume histogram(DVH).The dose homogeneity index(HI)of the target area was calculated,and the single rotation time and total treatment time of each plan were recorded and counted.SPSS 27.0 software was used for statistical analysis.Results No significant threading effect appeared regardless of the pitch value when the lead gate width was 1.0 cm.The threading effects in the experimental group were weaker than those in the control group when the lead gate width was 2.5 or 5.0 cm.The threading effect gradually rose with the pitch increased when the lead gate width was 5.0 cm.The most significant difference was found between the threading effect in case of the screw pitch being 0.500 and that with the screw pitch being 0.143,with the differenes being statistically obvious(P<0.05).The lead gate width had significant effects on the Dmax,Dmin,Dmean and HI of PTV1 and PTV2.When the lead gate width was 5.0 cm,high HI value and uneven dose distribution were detected and lowered screw pitch weakened the threading effect.The single rotation time first remained constant and then increased with the screw pitch was enlarged,with the changing points occurring in case of the screw pitches of 0.287 and 0.430.With a certain lead gate width,the treatment time for plans was shortened with the decrease of the pitches in case of the pritches lower than 0.287,and tended to be constant after the screw pitches reached 0.287.The changes of the computational grid had no significant effects on the results of radiotherapy plans when the lead gate width and screw pitch were kept constant.Conclusion When designing a spiral tomotherapy plan with conventional doses,a lead gate width of 1.0 or 2.5 cm and a screw pitch of 0.287 or 0.430 should be selected in order to minimize the threading effect while ensuring the efficiency of plan implementation.[Chinese Medical Equipment Journal,2025,46(8):58-66]
4.Applications and prospects of needle-free injection technologies in vaccine delivery
Qiang YANG ; Yongfeng LI ; Xin SONG ; Huaji QIU ; Yuan SUN
Chinese Journal of Veterinary Science 2025;45(11):2525-2534
Needle-free injection(NFI)has emerged as a novel vaccine delivery technology,utilizing high-pressure jet streams to deliver vaccines into intradermal or subcutaneous tissues.In recent years,the application of this technology in the fields of medicine and veterinary medicine has a-chieved significant progress.Compared with traditional needle injection,the core advantages of NFI have been highlighted in several aspects:it has significantly improved vaccination efficiency,mak-ing it particularly suitable for mass vaccination campaigns;it has reduced animal stress;it has en-hanced the comfort of vaccination;it has more effectively induced immune responses;and it has a-voided the risk of needle contamination,thereby lowering the infection rate.However,NFI has also faced challenges such as high equipment costs,complex operation,and the need to improve market acceptance.Future research directions have focused on the development of new vaccines and adju-vants as well as the design and optimization of needle-free injectors to enhance their universality and safety among different populations.In summary,NFI has provided an important solution for the innovation of vaccine delivery systems by improving vaccination comfort and immune efficacy and has offered theoretical basis and technical references for its industrial development.
5.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
6.Indole-3-aldehyde-loaded inulin-based hydrogel for protection against radiation-induced intestinal injury
Tuo LI ; Feifei MA ; Jiebing GUAN ; Siyu XIE ; Ning WANG ; Ningning HE ; Huijuan SONG ; Jianguo LI ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(5):408-415
Objective:To explore the protective effects and mechanisms of an indole-3-acetaldehyde (I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury.Methods:The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer, and its biocompatibility was assessed via a CCK-8 assay. Eighteen C57BL/6 mice (aged: 6-8 weeks) were stratified by body weight and randomly assigned into three groups with 6 mice in each group: blank control, irradiation-only, and irradiation+ hydrogel protection. Abdominal irradiation was administered using 137Cs γ-rays at 17 Gy. The irradiation+ hydrogel protection group received 200 μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation. Meanwhile, the irradiation-only group was treated with an equivalent volume of sterile water via gavage. The mice were euthanized four days post-irradiation, and their intestinal tissues were harvested. Hematoxylin-eosin (HE) staining, Ki67 immunohistochemistry, and TUNEL immunofluorescence were performed to assess histopathological damage, epithelial cell proliferation, and apoptosis, respectively. Quantitative real-time PCR (qRT-PCR) was employed to measure mRNA levels of inflammatory and antioxidant factors. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results:The test results of the rheometer confirmed successful hydrogel formation. CCK-8 assays demonstrated excellent biocompatibility. Compared with the irradiation-only group, the irradiation+ hydrogel protection group exhibited preserved intestinal histoarchitecture, a 1.5-fold increase in intestinal cell proliferation ( t = 8.35, P < 0.05), and a 2-fold reduction in radiation-induced apoptosis ( t = 7.94, P < 0.05). Moreover, the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1 ( t = 3.16, 24.83, 5.92, P < 0.05), alongside reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α ( t = 5.15, 3.82, 3.83, P < 0.05). Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group. Conclusions:The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation, reduce radiation-induced apoptosis, and enhance both anti-inflammatory and antioxidant responses. In addition, it regulates gut microbiota composition and abundance, protecting against radiation-induced intestinal injury.
7.Advances in the application of PET/CT molecular imaging probes to the treatment of breast cancer
Huayu LI ; Jiaying SONG ; Tao YE ; Yucong WANG ; Lianfu WANG ; Qiang LI
Chinese Journal of Radiological Medicine and Protection 2025;45(5):497-502
Breast cancer, a malignant tumor that significantly endangers women′s health, has shown a gradually rising incidence in recent years. Some breast cancer patients experienced poor prognosis. The commonly used imaging techniques for breast cancer include ultrasound, mammography, and magnetic resonance (MR), which suffer from certain limitations in accurately diagnosing and staging breast cancer. Positron emission tomography/computed tomography (PET/CT) enables tumor imaging at the cellular and molecular levels by utilizing radiolabeled molecular probes targeting different ligands. This technique facilitates precise localization and qualitative diagnosis of lesions to improve the staging accuracy, thereby reducing biopsy frequency and enhancing treatment effects for patients. Therefore, PET/CT has gradually developed into an essential imaging method for breast cancer in clinical practice. It plays a critical role in assessing the extent of lesion invasion, predicting immune subtypes, and estimating targeted therapy efficacy, holding promising application prospects. Recently, significant research breakthroughs have been achieved in this field. This review summarized the advances in clinical applications of different PET/CT molecular probes in the diagnosis and treatment of breast cancer, aiming to enhance the understanding of this aspect.
8.Management strategies for vesicovaginal fistula following cervical cancer radiotherapy in women
Jiemin SI ; Weidong ZHU ; Ranxing YANG ; Lujie SONG ; Chongrui JIN ; Jianwen HUANG ; Xuxiao YE ; Zuowei LI ; Wenxiong SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(8):587-592
Objective:To investigate the treatment strategies for vesicovaginal fistula(VVF)in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches:Group A(11 patients):Underwent prone-position VVF repair. Mean age:(50.0±9.6)years;mean radiotherapy sessions:(22.6±2.2). All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them,1 patient previously received laparoscopic VVF repair,1 transvaginal VVF repair,and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery,the average daily usage of urine pads was 16.7(12.8,25.7)pieces,and the quality of life(QOL)score stood at 4.0(4.0,5.0)points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder,while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.2(0.8,1.6)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 3 cases of type 1,4 cases of type 2,2 cases of type 3,and 2 cases of type 4;7 cases of type A and 4 cases of type B;as well as 3 cases of typeⅠ,7 cases of type Ⅱ,and 1 case of type Ⅲ.Group B(20 patients):Underwent gracilis muscle flap packing for VVF repair. Mean age:(58.6±8.8)years;mean radiotherapy sessions:(29.8±3.9). Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions:3 had laparoscopic VVF repair,4 transvaginal VVF repair,and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery,the average daily usage of urine pads was 19.7(15.8,27.7)pieces,and the QOL score stood at 5.0(5.0,6.0)points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder,while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.8(1.0,3.2)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 4 cases of type 1,9 cases of type 2,3 cases of type 3,and 4 cases of type 4;6 cases of type A,11 cases of type B and 3 cases of type C;as well as 1 cases of type Ⅱ,and 19 case of type Ⅲ. Group C(2 patients):Underwent ureterocutaneous diversion. Ages:67 and 73 years;radiotherapy sessions:51 and 60,respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery,the daily usage of urine pads was 29 and 23 pieces,respectively,and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder,with diameters of 3 cm and 4 cm,respectively. Additionally,partial defects were noted in the ventral wall of the urethra,while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas,both cases were categorized as type 4,type C,and type Ⅲ. For Groups A and B,urinary catheters were indwelled for 3 weeks postoperatively,then removed to assess spontaneous urination and incontinence. QOL was evaluated,with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence,re-repair was performed 3?6 months later based on patient preference. For Group C,double-J stents were placed in the ureters,and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months,with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C,surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A:Follow-up duration:16.3(9.6,24.6)months. Surgical repair succeeded in 7 patients,with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence:2 refused further treatment,and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired,while one recurrence case refused further treatment. Group B:Follow-up duration:17.0(9.5,24.8)months(8?32 months). Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence:5 refused further surgery,and 2 underwent re-repair. One repair succeeded without incontinence,while one recurrence case refused treatment. Group C:Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence(no urine pads needed),and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3,respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general,patients who are younger,have received lower doses of radiation therapy,present with smaller fistula diameters,have well-vascularized and elastic perifistular tissues,and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair,have a history of at least two previous repair attempts,or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas,extensive pale and inelastic perifistular tissues,and who are not amenable to repair surgery undergo ureterocutaneous diversion.
9.CT imaging features of patients with chronic hydrocephalus after intracerebral hemorrhage and comparison of therapeutic effects of ETV and VPS
Shuai ZHANG ; Qiang PAN ; Zhenrui LIU ; Zongfei JIANG ; Feng SI ; Fengjia LI ; Chunyu SONG
Journal of Chinese Physician 2025;27(2):210-214
Objective:To investigate the computed tomography (CT) imaging features of patients with chronic hydrocephalus after intracerebral hemorrhage surgery and the difference between endoscopic third ventriculostomy (ETV) and ventricular peritoneal shunt (VPS).Methods:A total of 158 patients with intracerebral hemorrhage who received surgical treatment in the Department of Neurosurgery of the People′s Hospital of Jinan from January 2021 to June 2023 were retrospectively selected as the study objects, including 78 patients with chronic hydrocephalus after surgery as the hydrocephalus group, and 80 patients with no hydrocephalus after surgery as the non-hydrocephalus group, and the CT imaging data of the patients were statistically analyzed. Hydrocephalus group was divided into ETV group (42 cases) and VPS group (36 cases) according to different treatment methods. The efficacy and quality of life of the two groups were compared, and the incidence of complications in the two groups were counted.Results:There was no significant difference between hydrocephalus group and non-hydrocephalus group in the site of cerebral hemorrhage, hematoma morphology and the proportion of patients with mixed signs, lobular signs and black hole signs (all P>0.05). The proportion of patients with ventricular dilation and hematoma enlargement in hydrocephalus group was significantly higher than that in non-hydrocephalus group (all P<0.05). The National Institute of Health Stroke Scale (NIHSS) scores of hydrocephalus patients in the two groups were measured continuously at different time points, and there was no significant difference in NIHSS scores between the ETV group and the VPS group before treatment, at 2 weeks and 4 weeks of treatment (all P>0.05). There was no significant difference between the ETV group and the VPS group ( P>0.05). The recurrence rate of the ETV group was lower than that of the VPS group ( P<0.05). The quality of life scores of patients in ETV group were higher than those in the VPS group at 3 months and 6 months after surgery ( P<0.05). Conclusions:CT examination of patients with chronic hydrocephalus after intracerebral hemorrhage will show obvious characteristics of hematoma enlargement and ventricle enlargement. The efficacy of ETV and VPS in the treatment of chronic hydrocephalus after intracerebral hemorrhage surgery is similar, but the former has a lower recurrence rate and a higher postoperative quality of life.
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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