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.Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes.
Fan YU ; Yinfang TU ; Yanfang ZHANG ; Tianwei GU ; Haoyong YU ; Xiangyu MENG ; Si CHEN ; Fengjing LIU ; Ke HUANG ; Tianhao BA ; Siqian GONG ; Danfeng PENG ; Dandan YAN ; Xiangnan FANG ; Tongyu WANG ; Yang HUA ; Xianghui CHEN ; Hongli CHEN ; Jie XU ; Rong ZHANG ; Linong JI ; Yan BI ; Xueyao HAN ; Hong ZHANG ; Cheng HU
Chinese Medical Journal 2025;138(9):1129-1131
5.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
;
Humans
;
Consensus
;
Drugs, Chinese Herbal/therapeutic use*
;
Surveys and Questionnaires
6.Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods.
Xiao-Yan ZHENG ; Zi-Yi JIANG ; Yi-Ting LI ; Chao-Liang LI ; Hao ZHU ; Zheng YU ; Si-Yi YU ; Li-Li YANG ; Song-Yuan TANG ; Xing-Yu LÜ ; Fan-Rong LIANG ; Jie YANG
Journal of Integrative Medicine 2025;23(5):528-536
OBJECTIVE:
To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods.
METHODS:
In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator.
RESULTS:
The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups.
CONCLUSION
This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans
;
Female
;
Propensity Score
;
Embryo Transfer
;
Adult
;
Acupuncture Therapy
;
Retrospective Studies
;
Pregnancy
;
Live Birth
;
Birth Rate
;
Cohort Studies
7.Research status of risk prediction model of post-endoscopic retrograde cholangiopancreatography pancreatitis
Zhe-Yu ZHU ; Yi-Yu HU ; Peng CHEN ; Fei-Fan WU ; Si-Yu WANG ; Wei-Min WANG ; Chun-Mu MIAO ; Yun-Bing WANG ; Xiong DING
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1105-1109
Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.
8.The rh-CSF1 improves mitochondrial function and cell apoptosis in neurons under oxygen-glucose deprivation
Rui LIU ; Kuan FAN ; Pengju ZHANG ; Yu TIAN ; Wei SI ; Shirong LI ; Lu WANG ; Ran GU ; Xiao HU
Chinese Journal of Nervous and Mental Diseases 2024;50(8):489-494
Objective To investigate the mechanism by which Colony Stimulating Factor-1(CSF1)inhibits apoptosis in neurons subjected to oxygen-glucose deprivation(OGD).Methods Primary rat cortical neurons were divided into the OGD damaged neuron model group(OGD group),the rh-CSF1 intervention group(rh-CSF1 group),and control group.The sample size for each group was 3.After intervention with recombinant human CSF1(rh-CSF1),neuronal apoptosis rate and intracellular ATP content,reactive oxygen species levels,mitochondrial membrane potential,and mitochondrial DNA copy number were measured.The content of malondialdehyde within mitochondria and the activity of superoxide dismutase were also assessed.Results Intervention with rh-CSF1 increased mitochondrial membrane potential(0.55±0.03 vs.0.43±0.06,P<0.01),mitochondrial DNA copy number(0.88±0.05 vs.0.72±0.06,P<0.05),ATP content[(15.70±0.99)mmol/mg vs.(11.70±1.00)mmol/mg,P<0.01)],and superoxide dismutase[(18.47±1.38)U/mg vs.(14.78±1.81)U/mg,P<0.05)]activity in neurons injured by OGD.It also reduced levels of rectivereactive oxygen species(3.64±0.21 vs.4.45±0.33,P<0.05)and malondialdehyde within mitochondria[(2.13±0.19)mmol/mg vs.(2.78±0.20)mmol/mg,P<0.05)],and inhibited neuronal apoptosis(10.12±0.78 vs.17.04±1.23,P<0.01)Conclusion rh-CSF1 may alleviate the damage in neurons induced by OGD by improving mitochondrial function,reducing oxidative stress,and inhibiting cell apoptosis.
9.Impact of chaperone-mediated autophagy on bilirubin-induced damage of mouse microglial cells
Zhi-Fan PAN ; Si-Yu LI ; Ling LI ; Yan ZHANG ; Zi-Yu HUA
Chinese Journal of Contemporary Pediatrics 2024;26(4):385-393
Objective To investigate the effect of chaperone-mediated autophagy(CMA)on the damage of mouse microglial BV2 cells induce by unconjugated bilirubin(UCB).Methods The BV2 cell experiments were divided into two parts.(1)For the CMA activation experiment:control group(treated with an equal volume of dimethyl sulfoxide),QX77 group(treated with 20 μmol/L QX77 for 24 hours),UCB group(treated with 40 μmol/L UCB for 24 hours),and UCB+QX77 group(treated with both 20 μmol/L QX77 and 40 μmol/L UCB for 24 hours).(2)For the cell transfection experiment:LAMP2A silencing control group(treated with an equal volume of dimethyl sulfoxide),LAMP2A silencing control+UCB group(treated with 40 μmol/L UCB for 24 hours),LAMP2A silencing group(treated with an equal volume of dimethyl sulfoxide),and LAMP2A silencing+UCB group(treated with 40 μmol/L UCB for 24 hours).The cell viability was assessed using the modified MTT method.The expression levels of p65,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and cysteinyl aspartate specific proteinase-1(caspase-1)were detected by Western blot.The relative mRNA expression levels of the inflammatory cytokines interleukin(IL)-l β,IL-6,and tumor necrosis factor-α(TNF-α)were determined by real-time quantitative polymerase chain reaction.Levels of IL-6 and TNF-α in the cell culture supernatant were measured using ELISA.The co-localization of heat shock cognate protein 70 with p65 and NLRP3 was detected by immunofluorescence.Results Compared to the UCB group,the cell viability in the UCB+QX77 group increased,and the expression levels of inflammation-related proteins p65,NLRP3,and caspase-1,as well as the mRNA relative expression levels of IL-1β,IL-6,and TNF-α and levels of IL-6 and TNF-αdecreased(P<0.05).Compared to the control group,there was co-localization of heat shock cognate protein 70 with p65 and NLRP3 in both the UCB and UCB+QX77 groups.After silencing the LAMP2A gene,compared to the LAMP2A silencing control+UCB group,the LAMP2A silencing+UCB group showed increased expression levels of inflammation-related proteins p65,NLRP3,and caspase-1,as well as increased mRNA relative expression levels of IL-1 β,IL-6,and TNF-α and levels of IL-6 and TNF-α(P<0.05).Conclusions CMA is inhibited in UCB-induced BV2 cell damage,and activating CMA may reduce p65 and NLRP3 protein levels,suppress inflammatory responses,and counteract bilirubin neurotoxicity.[Chinese Journal of Contemporary Pediatrics,2024,26(4):385-393]
10.Relationship between heart rate variability, deceleration capacity and cardiovascular metabolic diseases in children and adolescents with normal weight obesity
Bo YU ; Kun SHI ; Xiaojuan ZHOU ; Xiaoyan WANG ; Lingxia FAN ; Feifei SI ; Yanfeng YANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(6):450-454
Objective:To investigate the relationship between heart rate variability(HRV), deceleration capacity(DC) and cardiovascular metabolic disease(CMD) in children and adolescents with normal weight obesity(NWO).Methods:A total of 200 children and adolescents aged 6-17 who underwent normal physical examination in Chengdu Women′s and Children′s Central Hospital from December 2022 to June 2023 were included in this retrospective case-control study.They were divided into the NWO group, normal weight lean(NWL) group, and overweight-obesity(OW-OB) group according to their body mass index(BMI) and body fat percentage(BF%).Fifty children were enrolled into the NWO group; fifty-one children were enrolled into the NWL group; and 99 children were enrolled into the OW-OB group.All the subjects received 24-hour heart monitoring, and their HRV indexes, such as the standard deviation of N-N interval in normal sinus(SDNN), the standard deviation of the mean value N-N intervals every 5-minute(SDANN), the mean of the standard deviations of all N-N intervals for each 5-minute segment of 24 hours(SDNNindex), the root mean square of successive N-N interval difference(rMSSD), the proportion of N-N 50(the successive N-N interval differences>50 ms) in the total number of N-N intervals(pNN50), and DC were automatically calculated.Blood pressure, fasting blood glucose and blood lipids were measured, and the cardiometabolic risk score(CRS) was obtained through the accumulation of relevant factors.The general data, SDNN, SDANN, SDNNindex, rMSSD, pNN50, DC and CRS of the three groups were compared by variance analysis.Spearman correlation and multivariate Logistic regression were used to analyze the risk factors affecting CRS.Results:There was no significant difference in age, gender and other general information among the three groups(all P>0.05).SDNN in the NWO, NWL, and OW-OB groups were(120.88±16.36) ms, (129.07±16.36) ms, and(109.29±16.38) ms, respectively( F=26.231, P<0.001); SDANN were(64.44±11.61) ms, (66.25±8.34) ms, and(61.70±6.85) ms, respectively( F=5.048, P=0.007); rMSSD were(27.02±3.87) ms, (27.51±5.92) ms, and(25.12±6.78) ms, respectively( F=3.328, P=0.038); pNN50 were(12.62±4.04)%, (13.39±2.26)%, and(11.22±2.93)%, respectively( F=9.099, P<0.001); DC were(4.83±0.20) ms, (4.94±0.33) ms, and(4.63±0.28) ms, respectively( F=23.496, P<0.001)and CRS was 0.94±0.87, 0.69±0.19 and 1.57±1.07, respectively( P<0.01).The differences between the three groups were statistically significant.Spearman correlation analysis showed that BMI( r=0.211, P=0.003) and BF%( r=0.558, P<0.001) were significantly positively correlated with CRS, while SDNN( r=-0.258, P<0.001) and DC( r=-0.499, P<0.001) were significantly negatively correlated with CRS.Multivariate Logistic regression analysis showed that BF%(95% CI: 0.098-0.265, P<0.001) and DC(95% CI: -3.962--1.391, P<0.001) were independent risk factors for predicting CMD. Conclusions:Increased BF% and decreased DC are independent risk factors for CMD.Analysis of body composition and HRV in children and adolescents can help to identify potentially high-risk groups more accurately, intervene early, and reduce the risk of CMD.

Result Analysis
Print
Save
E-mail