1.Bioinformatics analysis based on pelvic organ prolapse related aging genes of GEO Database and LASSO regression algorithm
Minqi NING ; Yong HE ; Bingshu LI ; Guotao HUANG ; Xiaohu ZUO ; Zhihan ZHAO ; Wuyue HAN ; Li HONG
Journal of Jilin University(Medicine Edition) 2024;50(1):178-187
Objective:To screen the aging genes closely associated with pelvic organ prolapse(POP)by bioinformatics techniques,and to clarify the potential clinical significance and value of key genes.Methods:Gene Expression Omnibus(GEO)Database was used to download the datasets GSE53868 and GSE151188 for POP-related genes with the keyword"pelvic organ prolapse".The aging-related genes were obtained from Aging Atlas,CellAge,and the Human Ageing Genomic Resources(HAGR)Databases;the intersection of genes related with POP in two groups provided a list of differentially expressed genes(DEGs)associated with aging in POP;gene Set Enrichment Analysis(GSEA)was conducted with R software version 4.2.1;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis of DEGs were conducted by the Database for Annotation,Visualization and Integrated Discovery(DAVID);the protein-protein interaction(PPI)network was constructed with Cytoscape 3.9.1 software;the top 10 Hub genes were selected by cytoHubba plugin;the infiltration of 22 types of immune cells in the patients in POP group and control group was analyzed by CIBERSORT deconvolution method using R software;the key genes were further screened by LASSO regression algorithm;the correlation and diagnostic efficacy between key genes and immune cell infiltration were analyzed.Results:From the Aging Atlas,CellAge,and HAGR Databases,724 aging-related genes were identified.Intersection with the POP expression profile yielded an aging gene expression matrix related to POP containing 624 genes,and 29 POP-related DEGs were identified after differential analysis,including 2 upregulated genes and 27 downregulated genes.The GSEA results showed that the upregulated pathways were mainly related to diabetes and cellular senescence,whereas the downregulated pathways included Alzheimer's disease and hypoxia-inducible factor-1(HIF-1)signaling pathways.The GO functional enrichment analysis mainly enriched in the biological processes such as the response of the cells to lipopolysaccharide,inflammatory response,and negative regulation of cell proliferation.The KEGG signaling pathway enrichment analysis mainly enriched in interleukin-17(IL-17),tumor necrosis factor(TNF),and nuclear factor-kappa B(NF-κB)signaling pathways.The PPI network analysis got 10 Hub genes including interleukin-6(IL-6),interleukin-1B(IL-1B),prostaglandin-endoperoxide synthase 2(PTGS2),and NF-kappa-B inhibitor alpha(NFKBIA).The CIBERSORT deconvolution method results showed a relatively higher infiltration proportion of neutrophils and activated mast cells in the patients in POP group,the activated mast cells had a positive correlation with most of the DEGs(r>0.5)and the macrophages had a significant positive correlation with IL-1B(r>0.6).The key genes Jun D proto-oncogene(JUND),Snail homolog 1(SNAI1),amphiregulin(AREG),Lamin A/C(LMNA),and superoxide dismutase 2(SOD2)selected by LASSO regression analysis had high diagnostic efficacies,and the area under receiver operating characteristic curve(ROC)(AUC)were all greater than 0.75.Conclusion:During the aging process,the genes such as JUND,SNAI1,AREG,LMNA,and SOD2 may participate in the pathophysiology of POP through various pathways,including inflammation-related pathways,transcription regulation,and affecting collagen secretion and metabolism,thereby influence the connective tissue support function and promote the occurrence and development of POP.
2.Artificial intelligence knowledge graph and image classification for quality control of chest posterior-anterior position X-ray radiograph
Qian WANG ; Liangliang SONG ; Xiao HAN ; Ming LIU ; Biao ZHANG ; Shibo ZHAO ; Zongyun GU ; Lili HUANG ; Chuanfu LI ; Xiaohu LI ; Yongqiang YU
Chinese Journal of Medical Imaging Technology 2024;40(6):922-927
Objective To observe the value of artificial intelligence(AI)knowledge graph and image classification for quality control(QC)of chest posterior-anterior position X-ray radiograph(abbreviated as chest film).Methods Totally 9 236 chest films from 595 medical institutions in Anhui province imaging cloud platform were retrospectively enrolled.QC knowledge graph containing 21 classification labels were constructed.Firstly,QC of chest films based on the above knowledge graph were performed by 10 technicians for 2 rounds of single person and 1 round of multi person,and the results were recorded as A,B and C,respectively.Then AI algorithms were used to classify and evaluate based on knowledge graph,and the result was recorded as D.Finally,a QC expert reviewed results C and D to determine the final QC results and taken those as references to analyze the efficiency of the above 4 QC.Results The area under the curve(AUC)of AI algorithm for QC of chest films were all ≥0.780,with an average value of 0.939.The average precision of QC for chest films of A,B,C and D was 81.15%,85.47%,91.65%and 92.21%,respectively.Conclusion AI knowledge graph and image classification technology could be effectively used for QC of chest posterior-anterior position X-ray radiograph.
3.Efficacy and safety of half-dose rituximab in the treatment of 23 cases with lupus nephritis
Yurong ZHAO ; Kunpeng LI ; Xiaohu DENG ; Xiaofei LIU ; Simin LIAO ; Jinshui YANG ; Xi ZHENG ; Jianglin ZHANG ; Feng HUANG ; Jian ZHU
Chinese Journal of Internal Medicine 2023;62(1):84-87
The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.
4.Induction of hepatocellular carcinoma in B6C3 (F1) mice chronicly exposed to trichloroethylene with enhanced acetylation of histone H2AK9ac and SET expression in the liver tissue
Shenpan LI ; Qunqun CHANG ; Xiaohu REN ; Nuanyuan LUO ; Haiyan HUANG ; Desheng WU ; Yungang LIU ; Jianjun LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(12):910-914
Objective:To establish an animal model of trichloroethylene (TCE) -induced liver cancer following chronic exposure and to understand the changes in SET expression and histone acetylation, potentially serving as a molecular mechanism for TCE-induced hepatocarcinogenesis.Methods:B6C3 mice at 6 weeks were treated with TCE at a series of doses (500, 1000 and 2000 mg/kg) by gastric gavage, with corn oil used as the negative control and carbon tetrachloride (CCl 4) as the positive control. The serum and liver were sampled for the determination of biochemical indexes and pathological examination after 56 weeks of chemical exposure. Western blot was used to determine the levels of SET, H2AK9ac and HDAC1 expression. Results:The overall survival rate of the mice in various groups was 90.4% (141/156) , with no statistical difference between groups ( P>0.05) . Compared with the negative control, the organ coefficient for the liver in the high dose TCE group and the positive control group were significantly increased ( P<0.05) . The levels of ALT, AST, LDH and BUN in the all the three TCE groups and the positive control were significantly higher than those in the negative control ( P<0.01) . CREA levels in the 1000 and 2000 mg/kg TCE groups were significantly higher than those in the negative control ( P<0.05) . Statistical increases in the incidence of hepatocellular carcinoma and the activities of ALT and AST in various doses of TCE-exposed mice as compared with the control were observed ( P<0.01) , in a dose-dependent manner. In the 1000 and 2000 mg/kg of TCE treated mice, levels of SET and H2AK9ac were increased ( P<0.05) , while HDAC1 was decreased ( P<0.05) , Compared to the tissue adjacent to liver cancer, in the 1000 and 2000 mg/kg TCE groups, the levels of SET were increased ( P<0.05) , while HDAC1 was decreased ( P<0.05) , and H2AK9ac increased in the 2000 mg/kg group. Conclusion:The hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.
5.Induction of hepatocellular carcinoma in B6C3 (F1) mice chronicly exposed to trichloroethylene with enhanced acetylation of histone H2AK9ac and SET expression in the liver tissue
Shenpan LI ; Qunqun CHANG ; Xiaohu REN ; Nuanyuan LUO ; Haiyan HUANG ; Desheng WU ; Yungang LIU ; Jianjun LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(12):910-914
Objective:To establish an animal model of trichloroethylene (TCE) -induced liver cancer following chronic exposure and to understand the changes in SET expression and histone acetylation, potentially serving as a molecular mechanism for TCE-induced hepatocarcinogenesis.Methods:B6C3 mice at 6 weeks were treated with TCE at a series of doses (500, 1000 and 2000 mg/kg) by gastric gavage, with corn oil used as the negative control and carbon tetrachloride (CCl 4) as the positive control. The serum and liver were sampled for the determination of biochemical indexes and pathological examination after 56 weeks of chemical exposure. Western blot was used to determine the levels of SET, H2AK9ac and HDAC1 expression. Results:The overall survival rate of the mice in various groups was 90.4% (141/156) , with no statistical difference between groups ( P>0.05) . Compared with the negative control, the organ coefficient for the liver in the high dose TCE group and the positive control group were significantly increased ( P<0.05) . The levels of ALT, AST, LDH and BUN in the all the three TCE groups and the positive control were significantly higher than those in the negative control ( P<0.01) . CREA levels in the 1000 and 2000 mg/kg TCE groups were significantly higher than those in the negative control ( P<0.05) . Statistical increases in the incidence of hepatocellular carcinoma and the activities of ALT and AST in various doses of TCE-exposed mice as compared with the control were observed ( P<0.01) , in a dose-dependent manner. In the 1000 and 2000 mg/kg of TCE treated mice, levels of SET and H2AK9ac were increased ( P<0.05) , while HDAC1 was decreased ( P<0.05) , Compared to the tissue adjacent to liver cancer, in the 1000 and 2000 mg/kg TCE groups, the levels of SET were increased ( P<0.05) , while HDAC1 was decreased ( P<0.05) , and H2AK9ac increased in the 2000 mg/kg group. Conclusion:The hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.
6.Analysis and prospect of free medication for severe mental disorders in Beijing
Yun CHEN ; Qingzhi HUANG ; Ying XYU ; Bin LI ; Rui XI ; Xiaohu HAN ; Yu ZHAO ; Keyue FU
Journal of Public Health and Preventive Medicine 2020;32(5):15-19
Objective To analyze the situation and changing trend of free medication service in Beijing from 2013 to 2020, and to propose policies and service improvement measures. Methods A retrospective survey was conducted in Beijing to collect and analyze the service subjects, service process, drug catalog, fiscal investment and patient participation of free medication in each district in recent years. Results Among the 16 districts of Beijing, 81.25% of the districts included the patients listed in Item (2) of Paragraph 2 of Article 30 of the Mental Health Law into the scope of free medication, and 75% of the districts broke the restriction that the service targets were registered residents in Beijing. 56.25% of the districts provided a variety of free medication modes, and 81.25% of the districts provided a mode of nearby community service. The catalog of free medications in various areas was still based on the Beijing catalog, and only 18.75% of the districts supplemented the list. In 2020, the total investment of free medicines and subsidies was 88.3768 million RMB, and the per capita investment was 1 616.02 RMB. The total cost showed an increasing trend year by year. From 2013 to 2020, the difference of per capita annual financial investment in drugs and subsidies was statistically significant (F=9.248, P<0.001). The per capita cost basically showed an increasing trend year by year except for individual years. In 2020, 54,688 patients participated in the free medication service in Beijing, and the participation rate was 67.23%. From 2013 to 2020, the difference of annual participation rate of patients was statistically significant (χ2=37098.759, P<0.001), and the number and proportion of patients increased year by year. Conclusion The practice of the district level has proved feasible to expand the scope of free medication service and to optimize the service process, which should be paid more attention in the future. With the continuous advancement of policies and services, the level of patient participation in various areas will tend to be relatively balanced after rising year by year.
7.Imaging dynamic observation of cured COVID-19 patients with imported coronavirus pneumonia
Xiaohu LI ; Haitao WANG ; Juan ZHU ; Xiaohui QIU ; Jinping ZHANG ; Guoquan HUANG ; Xiaosong ZENG ; Kewu HE ; Zongyu XIE ; Qizhong XU ; Bin LIU ; Yongqiang YU
Chinese Journal of Radiology 2020;54(5):435-439
Objective:To explore the imaging changes of lung lesions in patients with imported COVID-19 when reaching the discharge standard.Methods:The clinical and CT imaging data of 60 cured patients with imported COVID-19 and discharged from January to February 2020 in Anhui Province were retrospectively collected. At the initial diagnosis, 5 cases were mild, 53 were ordinary, and 2 were severe. The clinical characteristics of the patients and the characteristics of chest CT images at discharge were analyzed.Results:Fever (57 cases) and cough (55 cases) were the main symptoms in 60 patients. In 5 mild patients, 3 cases were negative in the whole course of CT examination, 2 cases were negative in the first time and abnormal in the second time. The first CT imaging features of 55 patients (53 common type and 2 severe type) were mainly bilateral lung involvement (51 cases), multiple lesions (33 cases), more common under the pleura (40 cases), and ground glass opacities were the most common (55 cases). The features of chest CT in clinical outcomes were that the ground glass shadow in the lung gradually faded and was completely absorbed (19 cases); the scope of ground glass shadow in the lung expanded and progressed to crazy-paving, consolidation shadow, and the lesion gradually absorbed again followed by fibrous cord shadows (27 cases); ground-glass opacities in the lungs quickly progressed to a consolidation and then slowly absorbed. Most of the lesions were accompanied by more residual fibrous cord shadows (4 cases). In 2 severe patients, the lesions in the lungs were larger ground glass, and a large amount of fibrous foci remained after slow absorption.Conclusions:Chest CT plays an important role in the diagnosis and treatment of imported COVID-19, and the degree of lung involvement seen on CT images is in good agreement with clinical outcome.
8. Imaging dynamic observation of COVID-19 patients cured by imported coronavirus pneumonia
Xiaohu LI ; Haitao WANG ; Juan ZHU ; Xiaohui QIU ; Jinping ZHANG ; Guoquan HUANG ; Xiaosong ZENG ; Kewu HE ; Zongyu XIE ; Qizhong XU ; Bin LIU ; Yongqiang YU
Chinese Journal of Radiology 2020;54(0):E012-E012
Objective:
To explore the imaging changes of lung lesions in patients with imported COVID-19 patients when reaching the discharge standard.
Method:
The clinical and CT imaging data of 60 patients with imported COVID-19 cured and discharged from January to February 2020 in Anhui Province were retrospectively collected. The clinical characteristics of the patients and the characteristics of chest CT images at discharge were analyzed.
Results:
Fever (57 cases) and cough (55 cases) were the main symptoms in 60 patients. At the initial diagnosis, 5 cases were mild, 53 were ordinary, and 2 were severe. In 5 light patients, 3 cases were negative in the whole course of CT examination, 2 cases were negative in the first time and abnormal in the second time. . The first CT imaging features of 55 patients (53 common type and 2 severe type)were mainly bilateral lung involvement (51 cases), multiple lesions (33 cases), more common under the pleura (40 cases), and ground glass opacities were the most common. (55 cases). The clinical features of chest CT in clinical outcomes are that the ground glass shadow in the lung gradually fades and was completely absorbed (19 cases); the scope of ground glass shadow in the lung expanded and progressed to crazy-paving, consolidation shadow, and the lesion gradually absorbs again followed by Fibrous cord shadows (27 cases); ground-glass opacities in the lungs quickly progressed to a consolidation and then slowly absorbed . Most of the lesions were accompanied by more residual fibrous cord shadows (4 cases). In 2 severe patients, the lesions in the lungs were larger ground glass, and a big amount of fibrous foci remained after slowly absorption.
Conclusion
Chest CT plays an important role in the diagnosis and treatment of imported COVID-19, and the degree of lung involvement seen on CT images is in good agreement with clinical outcome.
9. Analysis of the potential role of SET in chromium-induced malignant transformation cells based on quantitative proteomics
Zhihong CHEN ; Nuanyuan LUO ; Xiaohu REN ; Shuqi WANG ; Chao HUANG ; Yungang LIU ; Jianjun LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(3):169-173
Objective:
To investigate alteration of proteins profile in malignant transformation bronchial epithelial cells(16HBE-T) induced by hexavalent chromium[(Cr(VI))] and analyze the expression level of SET protein, then to provide some new insights for the carcinogenesis mechanism of Cr(VI).
Methods:
Total protein was extracted from 16HBE cells and was alkylated and desalinated before digested into peptides. The products were labeled with Tandem Mass Tag (TMT) and identified using LC-ESI-MS/MS.
Results:
A total of 3 517 proteins were found, expression differences greater than 1.5 or less 0.67 times were to found have 185 and 201 proteins, respectively. Gene enrichment analysis revealed that differential proteins were mainly involved in autophagy, DNA damage repair, RNA processing and other biological processes. Western blot results showed the expression level of SET was significantly increased while downregulated in histone H3K18/27 acetylation and p53 protein.
Conclusion
Proteins involved in multiple biological processes altered in 16HBE-T cells and regulation mode of SET inhibiting histone H3K18/27 acetylation regulating transcriptional activity of p53 may paly an important role in Cr(VI)-association carcinogenesis.
10. Trichloroethylene-induced abnormal methylation on promoter region of SET in hepatic L-02 cells
Jiawen RUAN ; Zhihong CHEN ; Weixue LU ; Hang ZHANG ; Xiaohu REN ; Xinfeng HUANG ; Jianhui YUAN ; Yungang LIU ; Jianjun LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(3):165-168
Objective:
To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells.
Methods:
L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP).
Results:
The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions.
Conclusion
The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.


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