1.Analysis of prognostic factors for clear cell adenocarcinoma of the uterine cervix based on the Surveillance, Epidemiology and End Results database
Zhiyan LIU ; Ruifeng XUE ; Yang WANG ; Jianhao GENG ; Rongxu DU ; Yongheng LI ; Weihu WANG
Cancer Research and Clinic 2024;36(3):161-166
Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.
2.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
3.An excerpt of EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease in 2024
Wenjing NI ; Nan GENG ; Xue BAI ; Jie LI
Journal of Clinical Hepatology 2024;40(8):1567-1574
In June 2024,the European Association for the Study of the Liver,the European Association for the Study of Diabetes,and the European Association for the Study of Obesity jointly released the latest edition of clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease(MASLD),which comprehensively elaborates on the definition,prevalence rate,natural disease history,screening,diagnosis,and treatment of MASLD and proposes 33 statements and 72 recommendations.This article gives an excerpt of the key points in this document.
4.Overexpression of BZW1 promotes invasion and metastasis of gastric cancer cells by regulating Wnt/β-catenin signaling and promoting epithelial-mesenchymal transition
Wenjing ZHANG ; Nuo ZHANG ; Zi YANG ; Xiaofeng ZHANG ; Aofei SUN ; Lian WANG ; Xue SONG ; Zhijun GENG ; Jing LI ; Jianguo HU
Journal of Southern Medical University 2024;44(2):354-362
Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.
5.Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms
Xiaohua CHEN ; Hui LU ; Ziliang WANG ; Lian WANG ; Yongsheng XIA ; Zhijun GENG ; Xiaofeng ZHANG ; Xue SONG ; Yueyue WANG ; Jing LI ; Jianguo HU ; Lugen ZUO
Journal of Southern Medical University 2024;44(9):1653-1661
Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.
6.Mining diagnostic markers of preeclampsia based on weighted gene co-expression network analysis
Ruiqian YAO ; Dong YU ; Geng XUE
Academic Journal of Naval Medical University 2024;45(12):1529-1539
Objective To mine valid information in public databases through bioinformatics analysis and machine learning models and to identify candidate genes related to preeclampsia,so as to improve the accuracy of early diagnosis and provide targets for pathogenesis,diagnosis and treatment research.Methods The RNA-seq datasets of placental tissue samples of preeclampsia patients and healthy pregnant women were retrieved from the Gene Expression Omnibus,and the gene expression matrix was obtained after data download,quality control,comparison and quantification through bioinformation analysis.The differentially expressed genes were screened by DESeq2 1.38.3,the enrichment pathway was determined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes,the co-expression network was constructed using weighted gene co-expression network analysis(WGCNA),and the machine learning prediction model was established by random forest algorithm.Results A total of 49 common differentially expressed genes were screened from placental tissue samples of 156 pregnant women(70 preeclampsia patients and 86 healthy pregnant women)in 4 datasets and they were significantly enriched in extracellular regions,positive regulation pathway of follicle-stimulating hormone secretion,hormone activity pathway,and cytokine-cytokine receptor interaction pathway,etc.The 49 differentially expressed genes were categorized into 7 co-expression modules by WGCNA,and key modules highly related to preeclampsia were identified.Six candidate key genes(fms related receptor tyrosine kinase 1[FLT1],pappalysin 2[PAPPA2],protein phosphatase 1 regulatory inhibitor subunit 1C[PPP1R1C],myosin ⅦB[MYO7B],long intergenic non-protein coding RNA 2009[LINC02009],and inhibin subunit α[INHA])were screened.The random forest model based on these 6 key genes had good predictive value for preeclampsia(area under curve was 0.978).Conclusion Preeclampsia may be associated with genes for hormone secretion,immune response,angiogenic factors,pregnancy-associated plasma proteins,and inhibin,and these genes may be candidate diagnostic markers of preeclampsia.
7.Overexpression of BZW1 promotes invasion and metastasis of gastric cancer cells by regulating Wnt/β-catenin signaling and promoting epithelial-mesenchymal transition
Wenjing ZHANG ; Nuo ZHANG ; Zi YANG ; Xiaofeng ZHANG ; Aofei SUN ; Lian WANG ; Xue SONG ; Zhijun GENG ; Jing LI ; Jianguo HU
Journal of Southern Medical University 2024;44(2):354-362
Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.
8.Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms
Xiaohua CHEN ; Hui LU ; Ziliang WANG ; Lian WANG ; Yongsheng XIA ; Zhijun GENG ; Xiaofeng ZHANG ; Xue SONG ; Yueyue WANG ; Jing LI ; Jianguo HU ; Lugen ZUO
Journal of Southern Medical University 2024;44(9):1653-1661
Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.
9.Understanding the Neural Mechanisms of Phonagnosia
Pingting LI ; Jing ZHENG ; Zixuan XUE ; Libo GENG
Journal of Audiology and Speech Pathology 2024;32(3):274-278
Voice recognition is a key skill for successful human communication,but patients with voice recog-nition defects often suffer from the inability to accurately identify the speaker's identity.Phonagnosia refers to the difficulty in identifying a speaker by voice alone when hearing ability is not impaired.From the perspective of brain injury,the symptoms can be divided into congenital phonagnosia and developmental phonagnosia,and congenital phonagnosia is related to the dysfunction of the functional connection between the temporal lobe and the amygdala.The damaged brain areas in patients with acquired speech recognition defect mainly include the temporal lobe and the frontal lobe.In the future,more attention should be paid to the screening methods,neural mechanisms and differ-ences between patients with speech recognition deficiency and other patients with hearing and cognitive impairment.
10.Distribution and drug resistance profiles of common bacterial isolates in intensive care unit of a hospital in Xi'an
Zeshi LIU ; Xue ZHANG ; Jing LEI ; Jian YIN ; Yanping ZHANG ; Yan GENG
Chinese Journal of Infection and Chemotherapy 2024;24(4):427-433
Objective To understand the distribution and drug resistance profiles of common clinical isolates in the intensive care unit(ICU)of a hospital in Xi'an.Methods A retrospective analysis was conducted on the antimicrobial susceptibility test results of clinical bacterial isolates in ICU of the Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2020 to December 31,2022.Results A total of 3 649 clinical isolates were isolated from the ICU,including 1 344(36.8%)strains of Gram-positive bacteria and 2 305(63.2%)strains of Gram-negative bacteria.The most common bacterial species were Klebsiella spp.(14.8%,540/3 649),Enterococcus spp.(14.3%,522/3 649),coagulase-negative Staphylococcus(12.3%,448/3 649),Acinetobacter spp.(12.0%,438/3 649),and Escherichia coli(11.6%,424/3 649).The prevalence of methicillin-resistant Staphylococcus aureus(MRS A),methicillin-resistant Staphylococcus epidermidis(MRSE),and methicillin-resistant coagulase-negative Staphylococcus(MRCNS)was 76.1%,82.4%,and 69.9%,respectively.MRSA,MRSE,and MRCNS strains showed significantly higher antimicrobial resistance rates than MSSA,MSSE,and MSCNS except for trimethoprim-sulfamethoxazole.No Staphylococcus strains were found resistant to vancomycin or linezolid.Enterococcus faecium demonstrated higher antimicrobial resistance rates than Enterococcus faecalis.No Enterococcus isolates were found resistant to vancomycin.Two strains of linezolid-resistant E.faecalis were identified.Klebsiella pneumoniae showed high resistance rates to imipenem and meropenem(38.4%and 40.2%,respectively).Less than 2.0%of the Escherichia coli strains were resistant to imipenem and meropenem,while more than 10.0%of the Enterobacter cloacae were resistant to imipenem and meropenem.About 27.1%and 19.6%of the Pseudomonas aeruginosa strains were resistant to imipenem and meropenem,respectively.Acinetobacter baumannii showed high resistance rates to imipenem and meropenem(86.0%and 86.7%,respectively).Conclusions K.pneumoniae and A.baumannii strains isolated from the intensive care unit showed high resistance rates to carbapenems.Other species of Enterobacterales are still susceptible to carbapenems at a low resistance rate.Linezolid-resistant strain was identified in Enterococcus spp.No cross resistance to vancomycin was found in Enterococcus isolates.Therefore,it is necessary to strengthen the surveillance of antimicrobial resistance and use antibiotics reasonably for controlling hospital infections.

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