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.Review on alcohol exposure associated embryonic stem cell differentiation mechanisms
Jing GAO ; Bingchun LIU ; Hong CHEN ; Peixin XU ; Xin GUO ; Jianlong YUAN ; Yang LIU
Journal of Environmental and Occupational Medicine 2025;42(5):637-643
Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.
4.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.
5.Association of participation in non-sports extracurricular tutoring classes with screening myopia and axial length among primary school students
Chinese Journal of School Health 2025;46(11):1544-1548
Objective:
To analyze the association of participation in non-sports extracurricular tutoring classes with the prevalence of screening myopia, axial length (AL) and axial length to corneal radius ratio (AL/CR) among primary school students, so as to provide evidences for formulating myopia prevention and control policies.
Methods:
In December 2024, combination of convenience and cluster sampling method was used to select 2 273 students from two primary schools in Hefei City, Anhui Province. Ophthalmic examinations and questionnaire surveys were conducted to obtain information on myopia, AL, AL/CR and participation in various types of extracurricular tutoring. A binary Logistic regression model was used to analyze the association between non-sports tutoring and screening myopia, and multiple linear regression models were used to examine the associations between non-sports tutoring and AL and AL/CR.
Results:
Among the surveyed students, the participation rate in non-sports extracurricular tutoring classes was 64.9% , and the overall prevalence of screening myopia was 39.1%. The average AL and AL/CR were (23.60± 1.01 ) mm and (3.00±0.12), respectively. Univariate analysis showed that students who attended non-sports, music, or academic tutoring classes for ≥2 h per week had higher risks of screening myopia and greater AL/CR values than non-participants (screening myopia: OR =1.38, 1.82, 1.55; AL/CR: β =0.01, 0.03, 0.03; all P <0.05). After adjusting for sex, grade, and participation in sports tutoring, multivariate analysis indicated that participation in non-sports and musical instrument tutoring classes for ≥2 h per week remained significantly associated with higher risks of screening myopia ( OR =1.26, 1.49, both P <0.05). Multiple linear regression showed that participation in musical instrument tutoring for ≥2 h per week was positively correlated with AL ( β=0.14, P < 0.05).
Conclusions
Participation in non-sports extracurricular tutoring is common among primary school students. Attending non-sports tutoring classes for ≥2 h per week increases the risk of screening myopia.
6.Three-dimensional finite element analysis of lumbar disc herniation under different body positions
Ben-Jing YIN ; Yu LU ; Fu-Tao JI ; Rong-Neng QIU ; Yuan-Yang XIE ; Ge CHEN ; Tian-Li XU ; Chao-Yu BAO ; Ju-Bao LI
China Journal of Orthopaedics and Traumatology 2024;37(6):599-604
Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.
7.Applied anatomical study of facial artery branches in the nasolabial groove area
Yuan CONG ; Jing-Wen LIU ; Xiao-Xu SUN ; Chun-Ju ZHANG ; Ai-She DUN
Journal of Regional Anatomy and Operative Surgery 2024;33(10):882-886
Objective To observe the course and diameter of facial artery branches and its adjacent structures in nasolabial groove area and the positional relationship,so as to provide reference for clinicians to carry out facial cosmetic repair surgery.Methods A total of 40 adult head and neck specimens were dissected on the spot,and the course and position of the facial artery branches,facial vein and facial nerve in the nasolabial groove area were observed,their diameters were measured,and relevant data were recorded.Results There were 4 types of facial artery branches in the nasolabial groove area:type Ⅰ(upper lip type)accounted for 12.5%,type Ⅱ(nasal type)accounted for 62.5%,type Ⅲ(classical type)accounted for 20.0%,and type Ⅳ(double severe type)accounted for 5.0% .There were 4 kinds of positional relationship between the facial artery and the facial vein in the nasolabial groove area:42.5% of the orofacial artery was located on the medial side of the facial vein,32.5% of the orofacial artery was located on the lateral side of the facial vein,17.5% of the two were close to and wrapped in a fascial sheath,7.5% of the orofacial artery and the main trunk of the facial vein were crossed,and the vein was located in the deep surface of the artery.There were 3 kinds of positional relationship between the facial artery and the marginal mandibular branch of the facial nerve:87.5% of the facial artery was deep on the marginal mandibular branch of the facial nerve,7.5% of the facial artery was superficial on the marginal mandibular branch of the facial nerve,and 5.0% of the facial artery was held or surrounded by two branches of the marginal mandibular branch of the facial nerve on the superficial or deep surface.Conclusion The positional relationship among facial artery,facial vein and facial nerve in the nasolabial groove area is complicated.Familiarity with its positional relationship can avoid damaging blood vessels and nerves during the nasorabial groove surgery,reduce surgical complications and improve surgical safety.
8.Trajectory of perioperative symptom cluster in middle-aged and elderly patients with gynecological malignant tumors: a longitudinal study
Xiuyun CUI ; Chunyan XU ; Jing ZHAO ; Jing SU ; Jing YUAN ; Jia ZHANG
Chinese Journal of Modern Nursing 2024;30(17):2323-2329
Objective:To explore the composition and trajectory of symptom clusters during perioperative period in middle-aged and elderly patients with gynecological malignant tumors, so as to provide reference for formulating symptom management programs.Methods:From December 2022 to September 2023, convenience sampling was used to select 145 middle-aged and elderly patients with gynecological malignant tumors who underwent surgical treatment at the Affiliated Cancer Hospital of Xinjiang Medical University as the study subject. A longitudinal survey was conducted on patients at four time points [1 day before surgery (T1), 1 day after surgery (T2), 3 days after surgery (T3), and 7 days after surgery (T4, before discharge) ] using the General Information Questionnaire and the Chinese version of the Anderson Symptom Inventory-Perioperative Module in Patients with Gynecological Cancer.Results:A total of 145 questionnaires were distributed, and 130 valid questionnaires were collected, with an effective response rate of 89.66% (130/145). Exploratory factor analysis extracted six symptom clusters, namely perimenopausal symptom cluster, psychological symptom cluster, fatigue-pain symptom cluster, gastrointestinal symptom cluster, energy deficiency symptom cluster, and surgery related symptom cluster. Perimenopausal symptom group was a specific symptom cluster of gynecological malignant tumor patients, existing at T1. Psychological symptom cluster persisted during the patient's perioperative period. Fatigue-pain symptom cluster and surgery related symptom cluster existed at T2 to T4. Gastrointestinal symptom cluster and energy deficiency symptom cluster existed at T2 and T3.Conclusions:Middle aged and elderly patients with gynecological malignant tumors have various symptoms during the perioperative period, and the symptoms can cluster at different time points. The number of symptom clusters increases with the progress of surgical treatment, while the core symptoms within the cluster remain relatively stable over time. Clinical nursing staff should pay attention to the dynamic changes in the patient's perioperative symptom cluster, adopt efficient and targeted management measures based on the trajectory of symptom clusters, and reduce the burden of perioperative symptoms on patients.
9.Predictive value of cystatin C and antithrombin Ⅲ for contrast-induced acute kidney injury in elderly hypertensive patients
Linsheng WANG ; Xudong ZHANG ; Yuan LU ; Jing ZONG ; Fangfang LI ; Luhong XU ; Wenhua LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(8):862-866
Objective To investigate the predictive value of Cys C and AT Ⅲ for CIAKI in elderly hypertensive patients with AMI after PCI.Methods A total of 911 elderly hypertensive patients with AMI undergoing emergency PCI in the Affiliated Hospital of Xuzhou Medical University from January 2019 to May 2023 were consecutively enrolled,and then randomly divided into a training group(731 cases)and a validation group(180 cases)in a ratio of 8∶2.According to the diagnostic criteria of CIAKI defined by the European Society of Urogenital Radiology,the patients of the training group were further divided into CIAKI subgroup(n=91)and non-CIAKI sub-group(n=640).The basic clinical data were compared between the CIAKI and non-CIAKI sub-groups and between the training and validation groups.Multivariate logistic regression analysis was used.ROC curve was drawn to analyze the predictive value of Cys C,ATⅢ and their combina-tion for CIAKI.Results Fasting blood glucose,TG,Cys C,and diuretics were independent risk factors(OR=1.116,95%CI:1.009-1.235;OR=1.786,95%CI:1.363-2.339;OR=13.360,95%CI:4.462-39.999;OR=10.606,95%CI:4.110-27.370),while LVEF and AT Ⅲ were protective factors(OR=0.932,95%CI:0.897-0.968;OR=0.949,95%CI:0.929-0.969)for CIAKI in eld-erly hypertensive patients after emergency PCI.The AUC value of Cys C and AT Ⅲ combined to-gether in predicting CIAKI after emergency PCI was 0.818(95%CI:0.773-0.863,P<0.01),which was better than either of them alone.When Cys C level ≥1.10 mg/L,the risk of CIAKI was increased with the increment of the level;when AT Ⅲ ≥69%,the risk of CIAKI was decreased with the increase of AT Ⅲ level.Conclusion High Cys C level and low AT Ⅲ level are independ-ent risk factors for CIAKI,and their combination can improve the accuracy of predicting CIAKI after emergency PCI in elderly patients with hypertensive AMI.
10.Effect mechanism investigation of herb-partitioned moxibustion on relieving colon inflammation in Crohn disease rats based on neutrophil extracellular traps
Chi LU ; Jing XU ; Yuan LU ; Luyi WU ; Chunhui BAO ; Zhe MA ; Rui ZHONG ; Zhaoqin WANG ; Kexin SUN ; Handan ZHENG ; Zhijun WENG ; Yan HUANG ; Huangan WU ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(3):173-183
Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.


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