1.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
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.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
5.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.
6.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
7.Distribution characteristics of bacterial communities in central air-conditioning ventilation systems of a Grade 3A hospital in Shanghai based on 16S rRNA sequencing
Jun NI ; Haiyun ZHANG ; Jian CHEN ; Lijun ZHANG ; Yongping LIU ; Xiaojing LI ; Yiming ZHENG ; Liping ZHANG
Journal of Environmental and Occupational Medicine 2025;42(6):732-739
Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.
8.Comparison of the efficacy of TiRobot orthopaedic robot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures
Xing-Long ZHAO ; Jian-Jun SHEN ; Kang-Hu FENG ; Zhi-Wei CHEN ; Yuan-Long SI ; Xuan ZHANG ; Guan-De WANG ; Xiang HAI
China Journal of Orthopaedics and Traumatology 2024;37(2):129-134
Objective To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures.Methods A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021.Among them,37 patients were treated with F screw internal fixa-tion,including 16 males and 21 females,aged47 to 64years old with an average of(53.87±5.28)years old;According to Pauwels classification,there were 1 case of type Ⅰ,19 cases of type Ⅱ,17 cases of type Ⅲ;8 cases of combined medical diseases;17 cases of falling,8 cases of traffic accident and 12 cases of falling from height;The time from injury to operation was 29 to 49 hours with average of(35.00±7.34)hours.Another 35 cases used internal fixation with an inverted triangle parallel nail,including 13 males and 22 females with an average age of 46 to 63 years old(52.36±5.05)years old;According to the Pauwels injury classifi-cation:there were 2 cases of type Ⅰ,21 cases of type Ⅱ,12 cases of type Ⅲ;6 cases of medical diseases,15 cases of falling in-jury,9 cases of traffic accident,11 cases of falling injury;The time from injury to operation was 30 to 45 hours with an average of(33.00±6.83)h.The intraoperative blood loss,operation time,intraoperative fluoroscopy times,follow-up time,fracture healing time,postoperative complications were observed and compared between the two groups.The hip joint function was e-valuated by Harris score at 6 months and 12 months after operation.Results There was no significant difference in operation time,intraoperative blood loss,intraoperative fluoroscopy times and other intraoperative data between two groups(P>0.05).Both groups were followed up regularly,and the follow-up time was 12 to 16 months.The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group(P<0.05).There was 1 case of femoral neck shortening in the F screw internal fixation group,1 case of nonunion,1 case of nail withdrawal,and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group.The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group(P<0.05).Conclusion Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures.It can significantly shorten the fracture healing time,reduce the incidence of postoperative complications,significantly improve hip joint function,and improve the quality of life.
9.Clinical study of constructing nomogram model based on multi-dimensional clinical indicators to predict prognosis of knee osteoarthritis
Xin WANG ; Cong-Jun YE ; Zhen-Zhong DENG ; Yan XUE ; Chen-Hui WEI ; Qing-Biao LI ; Yang-Ming LUO ; Jian-Zhong GAN
China Journal of Orthopaedics and Traumatology 2024;37(2):184-190
Objective To analyze the factors affecting the prognosis of patients with knee osteoarthritis,and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators.Methods The clinical data of 234 pa-tients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed,including 126 males and 108 females;age more than 60 years old for 135 cases,age less than 60 years old for 99 cases.Lysholm knee function score was used to evaluate the prognosis of the patients,and the patients were divided into good progno-sis group for 155 patients and poor prognosis group for 79 patients according to the prognosis.The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors.The patients were divided into experimental co-hort and verification cohort,the results of the multiple factor analysis were visualized to obtain a nomogram prediction model,the receiver operating characteristic curve(ROC),calibration curve and decision curve were used to evaluate the model's dis-crimination,accuracy and clinical benefit rate.Results The results of multivariate analysis showed that smoking,pre-treatment K-L grades of Ⅲto Ⅳ,and high levels of interleukin 6(IL-6)and matrix metallo proteinase-3(MMP-3)were risk factors for the prognosis of patients with knee osteoarthritis.ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95%CI(0.742,0.866)]and 0.786[(95%CI(0.678,0.893)],re-spectively.The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points,respectively.When the threshold probability value in the decision curve was set to 31%,the clinical benefit rates of the experimental cohort and validation cohort were 51%and 56%,respectively.Conclusion The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance,and can provide a reference for taking targeted measures to improve the prognosis of patients.
10.Comparison of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langen-beck approach in the treatment of posterior acetabulum wall fractures
Jin ZHANG ; Jian-Jun SHEN ; Xiang HAI ; Chuan-Yuan LIU ; Wen-Jie ZHOU ; Zhi-Wei CHEN
China Journal of Orthopaedics and Traumatology 2024;37(8):786-792
Objective To compare the clinical efficacy of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langenbeck(K-L)approach in the treatment of posterior acetabulum wall fractures and to explore a more optimal approach for the treatment of posterior acetabulum wall fractures.Methods Total of 26 patients with posterior ac-etabulum wall fractures were retrospectively analysed and divided into two groups:the posterior hemipelvectomy of the greater trochanter group(test group)and the standard K-L approach group(control group).In the test group,there were 24 patients including 16 males and 8 females with an average age of(42.00±4.52)years old,the time of injury to surgery was(6.75±1.15)d.In the control group,there were 23 patients including 16 males and 7 females with an average age of(41.00±5.82)years old,the time of injury to surgery was(7.09±1.20)days.The total hospital stay,length of incision,operation time,intraoperative bleeding,postoperative drainage,discharge,fracture reduction quality(Matta criteria),hip abduction muscle strength,hip func-tion(Merle d'Aubigne-Postel score),postoperative complications and the incidence of ectopic ossification were compared.Results All cases were followed up for 6 months.There was no significant difference in incision length,intraoperative bleeding and postoperative drainage between two groups(P>0.05).However,the operation time of the test group was shorter than that of the control group(P<0.05).There was no statistically significant difference in fracture reduction and hip function between two groups(P>0.05).The hip abduction muscle strength of test group was better than that of control group(P<0.05).In addition,there was no significant difference in the incidence of postoperative complications and heterotopic ossification between two groups(P>0.05).Conclusion Compared with the standard K-L approach,the posterior hemipelvectomy of the greater trochanter approach can shorten the operative time,has better recovery of the postoperative hip abduction muscle strength,ex-poses the view of the fracture involving the more comminuted posterior acetabulum wall or the fracture of the roof of the socket,improved the rate of fracture anatomical repositioning,provides a new idea for the clinical treatment of posterior acetabulum wall fractures,and allows patients to perform functional exercises at an early stage.

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