1.Comprehensive Analysis of the Expression, Prognosis and Function of TRAF Family Proteins in NSCLC.
Yixuan WANG ; Qiang CHEN ; Yaguang FAN ; Shuqi TU ; Yang ZHANG ; Xiuwen ZHANG ; Hongli PAN ; Xuexia ZHOU ; Xuebing LI
Chinese Journal of Lung Cancer 2025;28(3):183-194
BACKGROUND:
Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC.
METHODS:
RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database.
RESULTS:
The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members.
CONCLUSIONS
TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans
;
Carcinoma, Non-Small-Cell Lung/pathology*
;
Lung Neoplasms/mortality*
;
Prognosis
;
Gene Expression Regulation, Neoplastic
;
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*
2.The role of host protein RBM8A in the replication of pseudorabies virus
Xiangqi QIU ; Jingyu SUN ; Jianhang HE ; Xing YANG ; Xiuwen YANG ; Guoqing ZHUANG ; Aijun SUN
Chinese Journal of Veterinary Science 2025;45(10):2126-2132
RNA binding motif protein 8A(RBM8A)is an RNA binding protein,which is mainly in-volved in translation and cell cycle regulation.In addition,RBM8A is a core factor of the exon-junc-tion complex(EJC),which is highly expressed in cells,especially in cancer cells,and abnormally expressed in cytoplasm and nucleus.Studies have shown that RBM8A plays a key regulatory role in the replication process of some viruses,such as Flaviviridae viruses.Therefore,whether RBM8A is involved in the replication of pseudorabies virus(PRV)is unknown.Therefore,this study proved whether RBM8A is involved in the replication of PRV.In order to study the effect of RBM8A pro-tein on PRV replication,the eukaryotic expression plasmid pCAGGS-HA-RBM8A was designed and constructed to express RBM8A,and sh-RBM8A was simultaneously designed and constructed to overexpress and inhibit RBM8A.qRT-PCR and Western blot were used to detect the effect of RBM8A on PRV replication.At the same time,PRV-GB standard plasmid was constructed to make PRV proliferation standard curve.After overexpression and inhibition of RBM8A,DNA was ex-tracted.Virus copy number was calculated by qRT-PCR to further detect the effect of RBM8A on PRV replication.The results showed that overexpression of RBM8A inhibited PRV replication and decreased the copy number of the virus,while overexpression of shRBM8A promoted PRV replication and increased the copy number of the virus.This study shows that RBM8A can inhibit PRV replication,which provides reference for the functional study of RBM8A and lays a founda-tion for the mechanism of anti-PRV replication.
3.Health economics evaluation of inoculation of children with type b Haemophilus influenzae vaccine
Sisi CHEN ; Lu YANG ; Tian TANG ; Xinping ZHANG ; Huan QIN ; Chengfeng XIE ; Yi ZENG ; Fei CAO ; Hongying LI ; Feina DENG ; Zhengbo TU ; Xiuwen CHEN
Chinese Journal of Nosocomiology 2025;35(17):2651-2655
OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53%(42 cases)in both groups,and the female children accounted for 42.47%(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.
4.Identifying phenotypes of surgical site infection in patients after gastrointestinal surgery
Xufei ZHANG ; Yiyu YANG ; Meilin WU ; Zhiwu HONG ; Huajian REN ; Lei WU ; Xiuwen WU ; Jianan REN
Chinese Journal of Gastrointestinal Surgery 2025;28(1):67-74
Objective:Surgical site infection (SSI) is a common health care-related infection after gastrointestinal surgery. Once SSI occurs after surgery, it can significantly prolong the postoperative hospital stay, increase the cost burden of patients and society, and even endanger the life safety of patients. The purpose of this study was to investigate the clinical phenotypes of gastrointestinal surgery, identify the clinical characteristics of SSI, and provide reference for the prevention of SSI after gastrointestinal surgery.Methods:This is a multicenter prospective cohort study that collected clinical data from all adult patients undergoing gastrointestinal surgery from March 2021 to February 2022 at 42 hospitals in China, including baseline and perioperative characteristics. Based on the variables associated with SSI, latent class analysis (LCA) was used to explore the population characteristics of SSI.Results:In total, 16 087 patients were included in the study, of whom 345 (2.1%) developed SSI. LCA analysis revealed that patients undergoing gastrointestinal surgery were classified into four clinical phenotypes, including α (3851), β (1538), γ (6387), and δ (4311). Type α had minimal abnormality on related system functions (ASA score > 2: 4.5% [173/3851]), and mainly underwent appendix surgery (98.9% [3808/3851]). The postoperative SSI incidence of type α was 0.4% (16/3,851), which belonged to the group of SSI low risk. The abnormality of system functions of type β (ASA score > 2: 17.4% [268/1538]) was worse than that of type α. Type β mainly underwent stomach surgery (72.4% [1113/1538]), and its incidence of postoperative SSI was 1.2% (18/1538), belonging to the group of SSI medium risk. The ASA score of type γ (ASA score > 2: 18.0% [1148/6387]) was comparable to that of type β. Type γ mainly received colorectal surgery (colon surgery: 40.1% [2562/6387]; rectal surgery: 33.6%[2143/6387]), and its incidence of postoperative SSI was 1.7% (106/6387), belonging to the group of SSI medium risk. Type δ (ASA score > 2: 23.5%[1015/4311]) was the most serious type with the highest proportion of open surgery. Type δ mainly underwent small intestine (54.0%[2327/4311]) and stomach surgery (32.3% [1392/4311]) and had the highest incidence of SSI (4.8% [205/4311]) and the highest mortality rate (0.6% [24/4311]), belonging to the group of SSI high risk. Compared with type α and β, the median length of hospital stay (α, β, γ, and δ: 5.0 days, 9.6 days, 13.0 days, and 16.0 days, P<0.001) and postoperative hospital stay (α, β, γ, and δ: 4.0days, 6.0days, 8.3 days, and 10.0 days, P<0.001) of type γ and δ were significantly increased, and the median medical costs (α, β, γ, and δ: 14 178.7 yuan, 39 514.2 yuan, 62 893.0 yuan and 57 266.6 yuan, P<0.001) were also significantly increased. Conclusion:LCA analysis elucidated four clinical phenotypes of patients undergoing gastrointestinal surgery. Type α had a low risk of SSI. Type β and γ had a medium risk of SSI, and type δ had a high risk of SSI.
5.Reflections on the construction of public health discipline in the context of New Medical Sciences
Xiuwen YANG ; Fanwei SUN ; Zhaoyi LIU ; Hongyang ZHANG ; Qin LIU ; Chengzhi CHEN ; Jingfu QIU
Chinese Journal of Medical Education Research 2025;24(9):1218-1222
New Medical Sciences, as a crucial initiative in transforming and upgrading medical education and healthcare services in China, has promoted deep integration of public health with multiple disciplines. However, the public health discipline still faces numerous challenges such as disease prevention system reconstruction, insufficient technological innovation, and the shortage of professional talents. To address these issues, this paper discusses the current status, challenges, and development of the public health discipline in the context of New Medical Sciences, and proposes strategies including reforming talent cultivation models, enhancing practical capabilities, strengthening faculty development, promoting the innovation of scientific research and social service, actively utilizing artificial intelligence technology, and optimizing international cooperation. These measures aim to achieve innovative development in the public health discipline, and better serve the Healthy China strategy and global public health initiatives.
6.Health economics evaluation of inoculation of children with type b Haemophilus influenzae vaccine
Sisi CHEN ; Lu YANG ; Tian TANG ; Xinping ZHANG ; Huan QIN ; Chengfeng XIE ; Yi ZENG ; Fei CAO ; Hongying LI ; Feina DENG ; Zhengbo TU ; Xiuwen CHEN
Chinese Journal of Nosocomiology 2025;35(17):2651-2655
OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53%(42 cases)in both groups,and the female children accounted for 42.47%(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.
7.The role of host protein RBM8A in the replication of pseudorabies virus
Xiangqi QIU ; Jingyu SUN ; Jianhang HE ; Xing YANG ; Xiuwen YANG ; Guoqing ZHUANG ; Aijun SUN
Chinese Journal of Veterinary Science 2025;45(10):2126-2132
RNA binding motif protein 8A(RBM8A)is an RNA binding protein,which is mainly in-volved in translation and cell cycle regulation.In addition,RBM8A is a core factor of the exon-junc-tion complex(EJC),which is highly expressed in cells,especially in cancer cells,and abnormally expressed in cytoplasm and nucleus.Studies have shown that RBM8A plays a key regulatory role in the replication process of some viruses,such as Flaviviridae viruses.Therefore,whether RBM8A is involved in the replication of pseudorabies virus(PRV)is unknown.Therefore,this study proved whether RBM8A is involved in the replication of PRV.In order to study the effect of RBM8A pro-tein on PRV replication,the eukaryotic expression plasmid pCAGGS-HA-RBM8A was designed and constructed to express RBM8A,and sh-RBM8A was simultaneously designed and constructed to overexpress and inhibit RBM8A.qRT-PCR and Western blot were used to detect the effect of RBM8A on PRV replication.At the same time,PRV-GB standard plasmid was constructed to make PRV proliferation standard curve.After overexpression and inhibition of RBM8A,DNA was ex-tracted.Virus copy number was calculated by qRT-PCR to further detect the effect of RBM8A on PRV replication.The results showed that overexpression of RBM8A inhibited PRV replication and decreased the copy number of the virus,while overexpression of shRBM8A promoted PRV replication and increased the copy number of the virus.This study shows that RBM8A can inhibit PRV replication,which provides reference for the functional study of RBM8A and lays a founda-tion for the mechanism of anti-PRV replication.
8.Identifying phenotypes of surgical site infection in patients after gastrointestinal surgery
Xufei ZHANG ; Yiyu YANG ; Meilin WU ; Zhiwu HONG ; Huajian REN ; Lei WU ; Xiuwen WU ; Jianan REN
Chinese Journal of Gastrointestinal Surgery 2025;28(1):67-74
Objective:Surgical site infection (SSI) is a common health care-related infection after gastrointestinal surgery. Once SSI occurs after surgery, it can significantly prolong the postoperative hospital stay, increase the cost burden of patients and society, and even endanger the life safety of patients. The purpose of this study was to investigate the clinical phenotypes of gastrointestinal surgery, identify the clinical characteristics of SSI, and provide reference for the prevention of SSI after gastrointestinal surgery.Methods:This is a multicenter prospective cohort study that collected clinical data from all adult patients undergoing gastrointestinal surgery from March 2021 to February 2022 at 42 hospitals in China, including baseline and perioperative characteristics. Based on the variables associated with SSI, latent class analysis (LCA) was used to explore the population characteristics of SSI.Results:In total, 16 087 patients were included in the study, of whom 345 (2.1%) developed SSI. LCA analysis revealed that patients undergoing gastrointestinal surgery were classified into four clinical phenotypes, including α (3851), β (1538), γ (6387), and δ (4311). Type α had minimal abnormality on related system functions (ASA score > 2: 4.5% [173/3851]), and mainly underwent appendix surgery (98.9% [3808/3851]). The postoperative SSI incidence of type α was 0.4% (16/3,851), which belonged to the group of SSI low risk. The abnormality of system functions of type β (ASA score > 2: 17.4% [268/1538]) was worse than that of type α. Type β mainly underwent stomach surgery (72.4% [1113/1538]), and its incidence of postoperative SSI was 1.2% (18/1538), belonging to the group of SSI medium risk. The ASA score of type γ (ASA score > 2: 18.0% [1148/6387]) was comparable to that of type β. Type γ mainly received colorectal surgery (colon surgery: 40.1% [2562/6387]; rectal surgery: 33.6%[2143/6387]), and its incidence of postoperative SSI was 1.7% (106/6387), belonging to the group of SSI medium risk. Type δ (ASA score > 2: 23.5%[1015/4311]) was the most serious type with the highest proportion of open surgery. Type δ mainly underwent small intestine (54.0%[2327/4311]) and stomach surgery (32.3% [1392/4311]) and had the highest incidence of SSI (4.8% [205/4311]) and the highest mortality rate (0.6% [24/4311]), belonging to the group of SSI high risk. Compared with type α and β, the median length of hospital stay (α, β, γ, and δ: 5.0 days, 9.6 days, 13.0 days, and 16.0 days, P<0.001) and postoperative hospital stay (α, β, γ, and δ: 4.0days, 6.0days, 8.3 days, and 10.0 days, P<0.001) of type γ and δ were significantly increased, and the median medical costs (α, β, γ, and δ: 14 178.7 yuan, 39 514.2 yuan, 62 893.0 yuan and 57 266.6 yuan, P<0.001) were also significantly increased. Conclusion:LCA analysis elucidated four clinical phenotypes of patients undergoing gastrointestinal surgery. Type α had a low risk of SSI. Type β and γ had a medium risk of SSI, and type δ had a high risk of SSI.
9.Reflections on the construction of public health discipline in the context of New Medical Sciences
Xiuwen YANG ; Fanwei SUN ; Zhaoyi LIU ; Hongyang ZHANG ; Qin LIU ; Chengzhi CHEN ; Jingfu QIU
Chinese Journal of Medical Education Research 2025;24(9):1218-1222
New Medical Sciences, as a crucial initiative in transforming and upgrading medical education and healthcare services in China, has promoted deep integration of public health with multiple disciplines. However, the public health discipline still faces numerous challenges such as disease prevention system reconstruction, insufficient technological innovation, and the shortage of professional talents. To address these issues, this paper discusses the current status, challenges, and development of the public health discipline in the context of New Medical Sciences, and proposes strategies including reforming talent cultivation models, enhancing practical capabilities, strengthening faculty development, promoting the innovation of scientific research and social service, actively utilizing artificial intelligence technology, and optimizing international cooperation. These measures aim to achieve innovative development in the public health discipline, and better serve the Healthy China strategy and global public health initiatives.
10.The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism.
Lijian CHEN ; Kaikai ZHANG ; Jiali LIU ; Xiuwen LI ; Yi LIU ; Hongsheng MA ; Jianzheng YANG ; Jiahao LI ; Long CHEN ; Clare HSU ; Jiahao ZENG ; Xiaoli XIE ; Qi WANG
Acta Pharmaceutica Sinica B 2024;14(11):4832-4857
Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.

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