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.Efficacy evaluation of denosumab in the treatment of patients with postmenopausal osteoporosis at high risk of fracture
Jing ZHOU ; Xingyun HOU ; Tingting LIU ; Jiaoyang ZHENG
Chinese Journal of Clinical Medicine 2025;32(1):85-92
Objective To explore the difference of efficacy and safety between denosumab and zoledronic acid in the treatment of patients with postmenopausal osteoporosis (PMOP), and to optimize the medication regimen for PMOP patients. Methods A total of 123 PMOP patients with high risk of fracture at the Second Affiliated Hospital of Naval Medical University from September 2021 to March 2024 were selected and randomly divided into two groups: the denosumab group (n=63) and the zoledronic acid group (n=60). Both groups underwent one-year treatment and follow-up, bone metabolism indexes, lumbar vertebrae, femoral neck, and total hip bone mineral density (BMD) were monitored, and any adverse reactions were documented. Results After treatment, the lumbar vertebrae and total hip BMD of patients in the denosumab group and the zoledronic acid group were significantly improved (P<0.05); the femoral neck BMD of patients in the zoledronic acid group was also significantly improved (P<0.05). The improvement of lumbar vertebrae BMD in the denosumab group was significantly better than that in the zoledronic acid group, while the improvement of femoral neck and total hip BMD in the zoledronic acid group was significantly better than that in the denosumab group (P<0.05). Bone metabolism indicators were significantly improved in both groups (P<0.05), and no significant liver and kidney dysfunction were observed. A total of 7 patients in the zoledronic acid group had mild adverse reactions and 5 patients in the denosumab group had mild adverse reactions. Conclusions Denosumab significantly increased lumbar vertebrae BMD and improved bone metabolism markers in PMOP patients, thus reducing risk of fracture and demonstrating good safety.
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.Development of nanographene oxide as clinical drug carrier in cancer therapy
Chun-Lian ZHONG ; Chang-Jian FANG ; Gui-Yu ZHOU ; Hui-Ling ZHU ; Tang ZHENG ; Wan-Jing ZHUANG ; Jian LIU ; Yu-Sheng LU
Chinese Pharmacological Bulletin 2024;40(8):1413-1418
Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.
6.Clinical effects of percutaneous elastic intramedullary nail assisted by arthrography for the treatment of radial neck fractures in children
Hui-Min ZHOU ; Yi-Wen XU ; Chun-Jie TAO ; Jiang-Rong FAN ; Jing-Yang YOU ; Jia-Cheng RUAN ; Si-Qi SHEN ; Zhen WANG ; Yong ZHENG
China Journal of Orthopaedics and Traumatology 2024;37(9):899-904
Objective To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children.Methods A retrospective analysis was performed on 23 chil-dren with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation(arthrography with elastic nail group)from January 2019 to December 2022,including 12 males and 11 fe-males,aged from 2 to 12 years old with an average of(7.36±1.89)years old;According to Judet fracture types,14 children were type Ⅲ and 9 children were type Ⅳ.In addition,23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation(elastic nail group),including 11 males and 12 females,aged from 2 to 14 years old with an average of(7.50±1.91)years old;Judet classi-fication included 15 children were type Ⅲ and 8 children were type Ⅳ.Operative time and intraoperative fluoroscopy times were compared between two groups.Metaizeau evaluation criteria was used to evaluate fracture reduction,and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups.Results Both groups were followed up for 12 to 24 months with an average of(16.56±6.34)months.Operative time and intraoperative fluoroscopy times of elastic nail group were(56.64±19.27)min and(21.13±7.87)times,while those of joint angiography with elastic nail group were(40.33±1 1.50)min and(12.10±3.52)times;there were difference between two groups(P<0.05).According to Metaizeau evaluation,11 patients got excellent result,9 good and 3 fair in joint angiography with elastic nail group,while in elastic nail group,5 ex-cellent,13 good,4 acceptable,and 1 poor;the difference between two groups was statistically significant(P<0.05).According to Tibone-Stoltz criteria,14 patients got excellent result,8 good,and 1 fair in joint arthrography with elastic nail group;while in elastic nail group,12 patients got excellent result,9 good,1 fair and 1 poor;there was no significant difference between two groups(P>0.05).Conclusion Compared to percutaneous elastic intramedullary nail fixation,closed reduction assisted by arthrography has advantages of reduced operation time,decreased intraoperative fluoroscopy frequency,and improved fracture reduction.Arthrography enables clear visualization of the anatomical structures of radius,head,neck,bone,and cartilage in children,facilitating comprehensive display of fracture reduction and brachioradial joint alignment.This technique more pre-cisely guides the depth of elastic intramedullary nail implantation in radius neck,thereby enhancing surgical efficiency and success rate.
7.Analysis of drug resistance and molecular characteristics of Listeria monocytogenes from food and clinical sources in Guizhou Province in 2022
Qian ZHOU ; Lian ZHENG ; Jing-Shu XIANG ; Jing-Yu HUANG ; Shu ZHU ; De-Zhu ZHANG ; Xin-Xu LUO ; Li ZHOU
Chinese Journal of Zoonoses 2024;40(7):613-619
This study was aimed at understanding the serotypes,virulence,drug resistance,and genetics of the pathogenic genes from 29 strains of foodborne Listeria monocytogenes in Guizhou Province in 2022.The minimum inhibitory concentration(MIC)values against eight antibiotics were determined with the microbroth dilution method,and whole genome sequencing was performed on 29 L.monocytogenes strains isolated from food microbiology and foodborne disease surveillance efforts in the province in 2022.The genome sequences were assembled,and bioinformatics analyses were conducted to examine genealogy,serogroups,sequence analysis(ST type),clonal groups(CC type),resistance genes,and virulence genes.A total of 29 strains of L.monocytogenes had resistance to zero to eight antibiotics,and carried six resistance genes.All strains of L.monocytogenes carried fosX,mprF,Lin,and norB.The 29 strains of L.monocytogenes belonged to 2 lineages(Ⅰ and Ⅱ):17 strains belonged to lineage Ⅱ,which was the dominant strain,and 12 strains belonged to lineage Ⅰ.The strains were classified into 13 ST types,among which ST8 was dominant,accounting for 31.03%(9/29 strains),and was followed by ST619 and ST121,accounting for three strains each.The strains were di-vided into four serogroups,with 15 strains in serogroups 1/2a and 3a;11 strains in serogroups 1/2b,3b,and 7;2 strains in serogroups 1/2c and 3c;and 1 strain in serogroups 4b,4d,and 4e.The strains were divided into 12 CC types,and one unsub-divided CC type,ST2348,among which CC8 was dominant,accounting for 27.59%(nine strains).A total of 25 virulence genes were found,which belonged to three virulence islands(LIPI-1,LIPI-2,and LIPI-3)and 23 CL types,including one or two strains each,and three CL types including two strains each.Foodborne L.monocytogenes in Guizhou Province has a low level of drug resistance,carries a high number of virulence genes,and shows genetic diversity in serogroups and molecular phe-notypes.These findings should strengthen the continuous surveillance efforts for Listeria monocytogenes.
8.Genomic analysis of human quinolone resistant 1,4,5,12:i:-Salmonella in Jiangsu Province from 2014 to 2018
Dong-Yu ZHENG ; Kai MA ; Yi-Jing ZHOU ; Gao-Lin WU ; Xiang HUO ; Xin QIAO
Chinese Journal of Zoonoses 2024;40(8):739-744
The molecular epidemiological characteristics of 1,4,[5],12:i:-Salmonella in Jiangsu Province were analyzed through whole genome sequencing(WGS).The distribution characteristics of related genes were obtained on the basis of anno-tated drug-resistant genes and plasmid types in the whole genome.Analysis of the molecular epidemiological characteristics of strains with cgMLST revealed possible modes of transmission of quinolone resistance in 1,4,[5],12:i:-Salmonella.Eleven cat-egories of antibiotic resistance genes(ARGs)were annotated among the fluoroquinolone-resistant strains.The detection rate of aminoglycoside ARGs was highest(100%).Twelve quinolone-resistant strains(92.3%)carried the IncHI2/IncHI2A plasmid type.PMQR gene analysis of various strains indicated that the strains from the United States and Europe carried six types of PMQR genes,and the detection rate of qnrB19 was highest.The Jiangsu strains carried three PMQR gene types,and the de-tection rate of aac(6')-Ib-cr was highest(11.84%).Analysis of cgMLST loci from different countries/regions revealed three main epidemic clusters.Some isolates from Jiangsu province might have the same evolutionary origin as some isolates from Eu-rope and the United States,and national/regional differences were observed in the PMQR gene carriage level.
9.Summary of the best evidence for peripheral arterial catheters placement and management in pediatric intensive care unit
Min ZHOU ; Qin FU ; Linjuan WANG ; Zerui ZHENG ; Chuhao ZHANG ; Xiaozhen ZHENG ; Jing JING
Chinese Journal of Nursing 2024;59(10):1255-1262
Objective To retrieve,evaluate and summarize the best pertinent evidence on the placement and management of peripheral arterial catheters in critically ill children at home and abroad for clinical references.Methods A systematic search was conducted in related databases on the evidence of the placement and management of peripheral arterial catheters in critically ill children.The spectrum of eligible documents included clinical decisions,guidelines,evidence summaries,systematic reviews,expert consensuses,and norms.The search period was from the establishment of the databases to April 30,2023.The included literature was limited to English and Chinese languages.The quality of the literature was independently evaluated by evidence-based trained investigators and combined with professional judgment to extract information from the literature that met the quality standards.Results A total of 18 articles were included,including 3 guidelines,3 clinical decisions,8 evidence summaries,3 systematic reviews and 1 expert consensus.The best evidence included a total of 27 pieces of evidence in 4 areas,namely the assessment of indwelling peripheral arterial catheters,placement of peripheral arterial catheters,maintenance during the duration of indwelling peripheral arterial catheters,and removal.Conclusion This study summarized the most robust evidence pertaining to the management of peripheral arterial catheters in critically ill children,and provided an evidence-based basis for the standardized placement and management of peripheral arterial catheters in critically ill children.Nursing staff should carefully select and apply evidence according to the actual clinical situation,the wishes of children and parents.
10.Association between body health score and the risk of hypertension among health examination population aged 40-65 years
Dashan WANG ; Li ZHENG ; Jing ZHOU ; Jin HU ; Yue MENG ; You LI ; Die WANG ; Junhua WANG ; Ziyun WANG
Chinese Journal of Health Management 2024;18(8):581-586
Objective:To analyze the association between body health score and the risk of hypertension among health examination population aged 40-65 years.Methods:This study was a cross-sectional study, and 1 104 people aged 40-65 years who underwent physical examination at the Physical Examination Centre of the First People′s Hospital of Fuquan City from March to November 2022 were selected. Clinical data, such as general information, physical examination, body composition and history of hypertension diseases, were collected. The body health score was reported by the Xiaomi Body Fat Scale′s accompanying exercise health software, and was calculated by combining body fat, water and other body composition data. The association between body health score and the risk of hypertension was analyzed using restricted cubic spline regression models, while a sensitivity analysis and sex-stratified analyses were performed. Multivariate logistic regression combined with stratified analysis was used to explore the association between dimensions of body composition and the risk of hypertension.Results:The body health score was significantly lower in hypertensive patients than in non-hypertensive patients among the 1 104 health examination population [52.0(30.0) vs 69.0(35.8) points] ( Z=-8.547, P<0.001). The lower the body health score, the higher the risk of hypertension ( χ2=18.48, PNonlinear<0.001). In the total population, high body mass index was associated with an increased risk of hypertension ( OR=1.744, 95% CI: 1.104-2.765), high protein content was associated with a reduced risk of hypertension ( OR=0.587, 95% CI: 0.344-0.982) (both P<0.05). Gender-stratified analyses showed that high protein content was associated with a reduced risk of hypertension only in men ( OR=0.233, 95% CI: 0.080-0.592) ( P=0.004). High body mass index was positively associated with the risk of hypertension when the body health score was ≥60 points ( OR=2.378, 95% CI: 1.255-4.542) ( P=0.008). High visceral adiposity index (VAI) was positively associated with the risk of hypertension when the body health score was <60 points ( OR=4.395, 95% CI: 1.466-13.620), and high protein content was negatively associated with the risk of hypertension ( OR=0.255, 95% CI: 0.091-0.638) (all P<0.05). Conclusions:Health examination population aged 40-65 years with lower scores of physical health are more likely to have a risk of hypertension. Men should pay attention to the impact of body protein in hypertension risk prevention and control. The effect of body mass index should be noted when body health scores are ≥60 points, and the effect of VAI and body protein should be considered when body health scores are <60 points.

Result Analysis
Print
Save
E-mail