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.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.
3.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.
4.Molecular evolution of human infection with H9N2 subtype avian influenza virus in Anhui province from 2013 to 2022
Yidan XIA ; Sitian YANG ; Minhao HU ; Xue ZHOU ; Junling YU ; Wanrong LUO ; Weixi FANG ; Jun HE
Chinese Journal of Experimental and Clinical Virology 2024;38(5):527-532
Objective:To analyze the genetic and molecular characteristics of H9N2 subtype avian influenza viruses from external environment and humans in Anhui Province from 2013 to 2022.Methods:Environmental samples and human samples were collected from Anhui influenza surveillance network laboratory. Sixty-three strains of virus were isolated in chicken embryos. RT-PCR was used to amplify the virus and whole genome sequencing was performed. To construct gene evolutionary tree and analyze its genetic characteristics and potential glycosylation sites.Results:The hemagglutinin (HA) gene belongs to the 9.2.4.5 clade, and the protein cleavage sites are mostly " PSRSSR\GL". The neuraminidase (NA) gene, basic protein-1(PB1) gene, acidic protein (PA) gene, non-structural protein (NS) gene and nucleoprotein (NP) gene belong to the F/98 clade, the matrix protein (MP) gene belongs to the G1/97 clade, and the basic protein-2 (PB2) gene belongs to the ST/7488 clade. Mutations of T155N, R164Q, H183N, T189D/V, A190V/T and Q226L occurred in HA protein, deletion of NA protein occurred at 62-64 sites, and mutations of T271A, I292V/M and E627V/L occurred in PB2 protein. At the same time, mutations of K356R and S409N occurred in the PA protein.Conclusions:The H9N2 subtype avian influenza viruses collected from external environment and human sources in Anhui province from 2013 to 2022 belong to the same evolutionary branch, and amino acid site mutations suggest that the virus shows a tendency to gradually adapt to the mammalian host environment. Therefore, further studies on the adaptive evolution of the virus and related monitoring work are needed.
5.Effects of preoperative anxiety on intraoperative body temperature and incision healing in radical mastectomy under general anesthesia in the elderly
Yu-Chun YANG ; Jiao-Qing WU ; Ting-Ting LIANG ; Yu-Ping HU ; Ti-Jun DAI
Journal of Regional Anatomy and Operative Surgery 2024;33(6):525-528
Objective To explore the effects of preoperative anxiety on intraoperative body temperature,adverse reactions during recovery and incision healing in elderly patients undergoing radical mastectomy under general anesthesia.Methods A total of 139 elderly patients who underwent radical mastectomy under general anesthesia in the Fourth Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were selected as the study objects,and they were divided into the non-anxiety group(87 cases)and the anxiety group(52 cases)according to whether they were complicated with anxiety before surgery.The nasopharyngeal temperature before surgery,after 30 minutes,60 minutes,90 minutes of surgery and at the end of surgery,the ratio of intraoperative nasopharyngeal temperature<36.0℃,the ratio of perioperative blood loss>300 mL,the occurrence of adverse reactions during the recovery period and the incision healing of patients in the two groups were compared.Results There was no statistically significant difference in the nasopharyngeal temperature before surgery and after 30 minutes of surgery of patients between the two groups(P>0.05).After 60 minutes,90 minutes of surgery and the end of surgery,the nasopharyngeal temperatures of patients in the anxiety group were lower than those in the non-anxietey group,and the differences were statistically significant(P<0.05).There were statistically significant differences in the nasopharyngeal temperature at different times of patients in the two groups(P<0.05).The ratios of patients with intraoperative nasopharyngeal temperature<36.0℃and perioperative blood loss>300 mL in the anxiety group were higher than those in the non-anxiety group,and the differences were statistically significant(P<0.05).The incidence of delayed awakening,shivering reaction,and poor postoperative incision healing in the anxiety group were higher than those in the non-anxiety group,with statistically significant differences(P<0.05).Conclusion Elderly patients undergoing radical mastectomy under general anesthesia combined with anxiety show obvious temperature drop after 60 minutes of surgery,and perioperative blood loss has significantly increased,with a higher incidence of intraoperative hypothermia,adverse reactions during recovery and poor postoperative incision healing,which should arouse clinical attention.
6.Ultrasonic anatomical study and clinical application of stellate ganglion block via C7 transverse process
Ai-Li HU ; Jun-Li WANG ; Xiao-Ai CHU ; Jie-Qing CHEN ; Zong-Yu ZHA ; Da-Sheng LU ; Qin-Zhong XIA
Journal of Regional Anatomy and Operative Surgery 2024;33(7):571-575
Objective To investigate the high-frequency ultrasonic anatomical features of the adjacent C7 transverse process and its clinical value in stellate ganglion block(SGB).Methods High-frequency ultrasound was applied to obtain ultrasonographic anatomical sonogram features in the plane of bilateral C7 transverse processes in 52 cases(104 sides in total)of healthy adults and then stored for the operator to learn and correctly label each tissue structure.Fifty patients who underwent ultrasound-guided SGB were selected and divided into the BC7 group(25 cases before study)and AC7 group(25 cases after study).The operation time,SGB success rate,number of adjusted needle tips,dosage of anaesthetic and adverse reaction of patients in both group were recorded.Results The main muscles observed in the C7 plane were the longissimus and anterior scalene muscles,the ultrasonographic anatomical relationships of the vagus nerve located in the carotid sheath,the pleura located posterior to the subclavian artery,and the recurrent laryngeal nerve located in the vicinity of the branches of the inferior thyroid artery are described,and the stellate ganglion was illustrated as a flattened hypoechogenic structure visible on the deep surface of the prevertebral fascia in the region of the external cervical longissimus muscle,vertebral artery and vein,and the medial aspect of the anterior oblique muscle,and emanated the sonographic features of several hypoechoic nerve bundles.Ultrasound guided SGB was completed uneventfully in patients of both groups,and all patients developed Horner syndrome,with the SGB success rate of 100%.The operation time[(5.36±1.11)minutes]of patients in the BC7 group was longer than that in the AC7 group[(3.08±0.86)minutes],the number of adjusted needle tips[(4.20±1.00)times]of patients in the BC7 group was more than that in the AC7 group[(2.24±0.87)times],and the dosage of anaesthetic[(1.82±0.28)mL]of patients in the BC7 group was more than that in the AC7 group[(1.64±0.22)mL],all the differences were statistically significant(P<0.05).There was no significant difference in the incidence of adverse reaction between the two groups(P>0.05).Conclusion After ultrasonic learning of adjacent structures through C7 transverse process,SGB is safe and easy to perform.
7.Safety and effectiveness analysis of laparoscopic radical resection of colorectal cancer without indwelling gastric tube
Yu-Fei HU ; Heng LI ; Jun-Feng OUYANG ; Yan FU
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1070-1073
Objective To evaluate the safety and effectiveness of laparoscopic radical resection of colorectal cancer without indwelling gastric tube during the perioperative period for postoperative rehabilitation of patients.Methods A total of 90 patients who underwent laparoscopic radical resection for colorectal cancer in our hospital from January 2021 to January 2023 were selected as the study objects,they were randomly divided into the observation group and the control group,with 45 cases in each group.The time of first postoperative exhaust and defecation,postoperative hospital stay,and the occurrence of complications such as throat pain,nausea and vomiting,pulmonary infection,intestinal obstruction,and anastomotic fistula of patients were compared between the two groups.Results The time of first postoperative exhaust and defecation and postoperative hospital stay of patients in the observation group were shorter than those in the control group,with statistically significant differences(P<0.05).The incidence of throat pain and nausea and vomiting of patients in the observation group was lower than that in the control group,with statistically significant difference(P<0.05);However,there was no statistically significant difference in postoperative complications such as pulmonary infection,intestinal obstruction,and anastomotic fistula of patients between the two groups(P>0.05).Conclusion Laparoscopic radical resection of colorectal cancer without indwelling gastric tube during the perioperative period will not increase the incidence of postoperative complications such as pulmonary infection,intestinal obstruction,and anastomotic fistula,instead,it can reduce the incidence of postoperative throat pain and nausea and vomiting,shorten hospital stay,and accelerate postoperative recovery of patients.
8.Effect of esketamine on tonsillectomy combined with endoscopic-assisted transoral adenoidectomy
Feng HU ; Jun SHI ; Ming ZHU ; Yuanyuan ZHAO ; Letao YU
China Journal of Endoscopy 2024;30(9):17-25
Objective To investigate the effect of esketamine on postoperative analgesia,stress response and serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)levels in children undergoing tonsillectomy(TE)combined with endoscopic-assisted transoral adenoidectomy(ETA).Methods 98 children with tonsil and adenoid hypertrophy from January 2023 to August 2023.They were divided into two groups randomly,with 49 cases in each group.Children in both groups received the same TE plus ETA treatment,and were given the same anesthesia induction and maintenance.The observation group was given 0.5 mg/kg of esketamine injection intravenously 20 min before the operation ended,while the control group same dose of normal saline intravenously.The operation and anesthesia recovery were observed in the two groups.The scores of the face,legs,activity,cry,consolability behavioral tool(FLACC)and pediatric anesthesia emergence delirium scale(PAED)were compared between the two groups immediately after extubation(T1),10 min after extubation(T2),20 min after extubation(T3),30 min after extubation(T4)and 60 min after extubation(T5).The stress response indicators and inflammatory reaction mediators were tested at the time entering the operating room(T0)and T5 time points.And the two groups were also compared in terms of adverse reactions.Results There were no significant differences in surgical duration,extubation time,wake-up time and length of postanesthesia care unit(PACU)stay between the two groups(P>0.05).The FLACC and PAED scores at T1,T2,T3,T4 and T5 time points in observation group were lower than those of the control group,the differences were statistically significant(P<0.05).The serum cortisol(Cor),angiotensin Ⅱ(Ang Ⅱ),tumor necrosis factor-α(TNF-α)and interleukin-iβ(IL-1β)levels of the two groups at T5 time point were higher than those at T0 time point,the differences were statistically significant(P<0.05).At T5 time point,the levels of serum Cor,Ang Ⅱ,TNF-α and IL-1β in observation group were lower than those of the control group,the differences were statistically significant(P<0.05).The incidence of adverse reactions in observation group was significantly lower than that in control group,the difference was statistically significant(8.16%and 24.49%,P<0.05).Conclusion Application of esketamine in the operation of TE combined with ETA in children can achieve exert good sedative and analgesic outcomes,and effectively reduce the stress response and inflammatory reaction caused by surgical trauma in children.
9.Lipidomic Analysis Revealed the Regulatory Mechanism of High Altitude Hypoxia on Phospholipid Metabolism in Mouse Spleen Tissue
Xin WANG ; Yu-Jing GUO ; Jia-Yang WANG ; Xiao-Jun WANG ; Ying HU
Chinese Journal of Biochemistry and Molecular Biology 2024;40(9):1289-1299
The spleen is the largest lymphoid organ of the body,which participates in the regulation of metabolic balance.High altitude hypoxia environment can affect lipid metabolism in spleen tissue,but the key mechanism of lipid metabolism is still unclear.We aimed to use lipidomic analysis to study the effect of high altitude hypoxia on lipid metabolism in mouse spleen tissue.C57BL/6 mice were placed at an altitude of 4 200 m and 400 m,respectively,and after 30 days the spleen tissues were harvested and lipidomic analysis was performed using an ultra-high performance liquid chromatography-Orbitrap mass spectrometry system.Under the high altitude hypoxia environment,the spleen index of mice and the white pulp decreased,and the germinal center expanded with other pathological changes.The results of lipidomic analysis showed that a total of 41 lipid subclasses and 2 473 lipid molecules were identified,and triacylglycerides(TGs)and phosphatidylcholines(PCs)were the two most identified lipid mole-cules.Using univariate and multivariate analysis,44 differentially expressed lipid molecules were identi-fied,which were mainly concentrated in phospholipid metabolism.Subsequently,RT-qPCR was per-formed on the key enzymes in the phospholipid metabolic pathway,and it was found that the mRNA ex-pression levels were different(P<0.05).It suggested that high altitude hypoxia environment mainly af-fects the phospholipid metabolism of mouse spleen tissue via reducing the contents of PC and phosphatidic acid(PA),promoting their conversion to phosphatidylethanolamine(PE)and cardiolipin(CL)and fa-cilitating the PE production via the CDP-Etn pathway.This study provides a new experimental basis for the abnormal metabolism of phospholipids in spleen tissue under high altitude hypoxia environment.
10.The impact of DRGs payment on Traditional Chinese Medicine hospitals:Based on difference-in-difference analysis
Hui-Jun GUO ; Jing LIU ; Guang-Yu HU ; Yi-Wei HAO ; Xin-Mei HAO ; Ya-Nan WANG ; Hui-Dong ZHU ; Qiu-Yan LI
Chinese Journal of Health Policy 2024;17(6):47-55
Objective:This study aims to evaluate the impact of Diagnosis-Related-Groups(DRGs)payment on the average total cost,length of stay,service volume,effectiveness,and characteristics of traditional Chinese medicine(TCM)hospitals.Methods:A national medical center specializing in TCM was selected as the research subject.The Difference-in-Difference Model(DID)was utilized to analyze the differences in various indicators between insured patients(intervention group)and uninsured patients(control group)before and after the implementation of the payment reform policy.The reliability and stability of the model were verified through parallel trend tests and placebo tests.Results:The coefficients of DID interaction terms for eleven indicators including average total hospitalization cost,number of cases,length of stay,proportion of medical service revenue,and proportion of herbal medicine revenue were significant(P<0.05).The DID interaction term coefficients for four indicators including herbal medicine usage rate and proportion of non-pharmacological TCM therapy revenue were not significant(P>0.05).Conclusion:DRG payment significantly reduced the per-admission cost,with significant decreases in consumables and medical technology expenses,optimizing cost structure,and a slight decrease in the proportion of herbal medicine costs.It is necessary to further expand the sample size,track policy impacts,and comprehensively evaluate the effects of DRG payment on TCM hospitals in China.

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