1.ADAR1 Regulates the ERK/c-FOS/MMP-9 Pathway to Drive the Proliferation and Migration of Non-small Cell Lung Cancer Cells.
Li ZHANG ; Xue PAN ; Wenqing YAN ; Shuilian ZHANG ; Chiyu MA ; Chenpeng LI ; Kexin ZHU ; Nijia LI ; Zizhong YOU ; Xueying ZHONG ; Zhi XIE ; Zhiyi LV ; Weibang GUO ; Yu CHEN ; Danxia LU ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2025;28(9):647-657
BACKGROUND:
Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.
METHODS:
Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism.
RESULTS:
ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression.
CONCLUSIONS
High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans
;
Lung Neoplasms/physiopathology*
;
Adenosine Deaminase/genetics*
;
Matrix Metalloproteinase 9/genetics*
;
Cell Proliferation
;
Carcinoma, Non-Small-Cell Lung/physiopathology*
;
Cell Movement
;
Animals
;
Mice
;
RNA-Binding Proteins/genetics*
;
Female
;
Male
;
Cell Line, Tumor
;
Proto-Oncogene Proteins c-fos/genetics*
;
Middle Aged
;
MAP Kinase Signaling System
;
Gene Expression Regulation, Neoplastic
;
Mice, Nude
;
Extracellular Signal-Regulated MAP Kinases/genetics*
2.Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.
Kuanyu XIA ; Lang MIN ; Wenqing XIE ; Guang YANG ; Dong Keon YON ; Seung Won LEE ; Ai KOYANAGI ; Louis JACOB ; Lee SMITH ; Jae Il SHIN ; Masoud RAHMATI ; Wenfeng XIAO ; Yusheng LI
Chinese Medical Journal 2025;138(13):1568-1577
BACKGROUND:
The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.
METHODS:
PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.
RESULTS:
Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.
CONCLUSIONS
In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans
;
Arthroplasty, Replacement, Knee/methods*
;
Osteoarthritis, Knee/surgery*
;
Randomized Controlled Trials as Topic
;
Treatment Outcome
3.Lower vs. standard starting dose oral roxadustat for treating anemia in Chinese patients with chronic kidney disease on dialysis: A prospective, randomized clinical trial.
Yan TU ; Yan XU ; Li YAO ; Beiru ZHANG ; Tiekun YAN ; Aiping YIN ; Xinzhou ZHANG ; Min YANG ; Jun LIU ; Caili WANG ; Xiaomei PENG ; Jianqin WANG ; Wei NIU ; Wenqing JIANG ; Bi-Cheng LIU
Chinese Medical Journal 2025;138(19):2520-2522
4.Analysis of the current status and influencing factors of frailty in patients aged 75 and above after percutaneous coronary intervention
Yang CHEN ; Shiyu WANG ; Chuan GAO ; Wenqing CAI ; Yajing SU ; Yumeng ZHANG ; Qingyin LI
Chinese Journal of Nursing 2025;60(13):1588-1595
Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16%.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P<0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P<0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.
5.Symptom management experience in patients with acute decompensated heart failure: a Meta-synthesis of qualitative studies
Wenqing CAI ; Baolin ZHANG ; Yang CHEN ; Yue HUO ; Chen ZHANG ; Yumeng ZHANG ; Yajing SU ; Wanjun CHEN ; Keping ZHU ; Qingyin LI
Chinese Journal of Modern Nursing 2025;31(25):3381-3388
Objective:To integrate the symptom management experiences of patients with acute decompensated heart failure (ADHF), so as to provide a basis for developing symptom management measures.Methods:Qualitative or mixed studies on the symptom management experience of ADHF patients included from establishment of the database to September 2024, were electronically retrieved in PubMed, CINAHL, Cochrane Library, Web of Science, Embase, EBSCO, China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database and other Chinese and English databases and gray literature databases. The quality of the literature was evaluated using the Critical Appraisal Skills Programme developed by the Center for Evidence-Based Medicine at the University of Oxford. The results were synthesized through the aggregative integration method.Results:A total of 14 papers were included. Thirty-four findings were distilled into eight categories and three integrative findings, namely, the multiple challenges posed by symptoms (complex and multiple symptomatic somatic experiences, symptom-induced mood changes, and reduced family and social engagement), the unmet needs of patients (insufficient healthcare resources, insufficient supply of discharge services provided by healthcare organizations, and lack of knowledge), and the co-existence of positive and negative coping styles (negative coping styles in symptomatic distress, positive debugging and diversified coping in symptomatic distress) .Conclusions:ADHF symptoms severely affect patients' physical, psychological, and social function. Healthcare professionals should focus on the unmet needs of patients with ADHF and explore patient-engaged models of active symptom management.
6.Symptom management experience in patients with acute decompensated heart failure: a Meta-synthesis of qualitative studies
Wenqing CAI ; Baolin ZHANG ; Yang CHEN ; Yue HUO ; Chen ZHANG ; Yumeng ZHANG ; Yajing SU ; Wanjun CHEN ; Keping ZHU ; Qingyin LI
Chinese Journal of Modern Nursing 2025;31(25):3381-3388
Objective:To integrate the symptom management experiences of patients with acute decompensated heart failure (ADHF), so as to provide a basis for developing symptom management measures.Methods:Qualitative or mixed studies on the symptom management experience of ADHF patients included from establishment of the database to September 2024, were electronically retrieved in PubMed, CINAHL, Cochrane Library, Web of Science, Embase, EBSCO, China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database and other Chinese and English databases and gray literature databases. The quality of the literature was evaluated using the Critical Appraisal Skills Programme developed by the Center for Evidence-Based Medicine at the University of Oxford. The results were synthesized through the aggregative integration method.Results:A total of 14 papers were included. Thirty-four findings were distilled into eight categories and three integrative findings, namely, the multiple challenges posed by symptoms (complex and multiple symptomatic somatic experiences, symptom-induced mood changes, and reduced family and social engagement), the unmet needs of patients (insufficient healthcare resources, insufficient supply of discharge services provided by healthcare organizations, and lack of knowledge), and the co-existence of positive and negative coping styles (negative coping styles in symptomatic distress, positive debugging and diversified coping in symptomatic distress) .Conclusions:ADHF symptoms severely affect patients' physical, psychological, and social function. Healthcare professionals should focus on the unmet needs of patients with ADHF and explore patient-engaged models of active symptom management.
7.Preoperative prediction of lymphovascular invasion in breast cancer with digital breast tomosynthesis-based intratumoral and peritumoral radiomics
Suxin ZHANG ; Haiyan LI ; Yiqun ZHENG ; Wenqing CHEN ; Sheng HE ; Caixian YANG ; Gang LIANG ; Jianding LI ; Zengyu JIANG
Journal of Practical Radiology 2025;41(1):46-51
Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.
8.Comparative study with propensity score matching of gastrectomy versus total gastrectomy for the safety and prognosis of Siewert types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction
Bo WANG ; Rui YANG ; Yun QIAO ; Maojie ZHANG ; Yinhao YANG ; Jie WANG ; Nan WANG ; Jinjie ZHANG ; Xiaonan WEI ; Peng CUI ; Wei WEI ; Yongai LI ; Yu WANG ; Wenqing HU
Chinese Journal of Gastrointestinal Surgery 2025;28(2):169-177
Objective:To compare the safety, number of lymph nodes removed, rate of lymph node metastasis, and prognosis between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with Siewert types II and III adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, clinical data of patients diagnosed with adenocarcinoma of the esophagogastric junction at Changzhi People's Hospital, affiliated with Changzhi Medical College, between December 2019 and November 2022, were collected. Patients who had received neoadjuvant therapy, had multiple malignant lesions in the stomach, had concomitant malignancies in other organs, had incomplete clinical data, or had been lost to follow-up were excluded. The study cohort comprised 308 patients, 99 in the PG group and 209 in the TG group. To reduce confounding bias, propensity score matching was performed, matching patients for age, sex, body mass index, tumor diameter, and pathological stage in a 1:1 ratio, resulting in 73 patients in each group. The primary outcomes assessed were operative details, number of lymph nodes dissected, rate of lymph node metastasis, postoperative complications, duration of hospital stay, and follow-up and survival outcomes.Results:The PG group had a significantly shorter median operative time than did the TG group (250 vs. 280 minutes, Z = -4.970, P<0.001), with fewer cases of intraoperative blood loss >100 mL (30.1%[22/73] vs. 46.6%[34/73], χ2=4.171, P=0.041), and a smaller number of lymph nodes removed (median 33 vs. 46, Z =-4.774, P<0.001); all of these differences are statistically significant (all P<0.05). Differences between the two groups in postoperative hospital stay and postoperative complications were not statistically significant (both P>0.05). Furthermore, no statistically significant differences were found between the PG and TG groups in the number of lymph nodes dissected or the lymph node metastasis rates at stations No. 1, No. 2, No. 3, No. 4sa, No. 4sb, and No. 7 (all P> 0.05). Among the 209 patients in the TG group, analysis of risk factors for metastasis to distal perigastric lymph nodes (No.4d, No.5, and No.6) showed that patients with tumor diameters ≤4 cm and T1–T3 stage disease had significantly lower rates of metastasis to these lymph nodes than did patients with tumor diameters >4 cm and/or T4 stage disease (0/78 vs. 12/131 [9.2%]); these differences are statistically significant ( P=0.014). The median duration of follow-up for the entire cohort was 26 months. The 3-year overall survival rates for the PG and TG groups were 62.5% and 63.3%, respectively; this difference is not statistically significant (χ 2=0.330, P = 0.565). Multivariate analysis showed that older age ( P = 0.035) and advanced pathological stage ( P = 0.018) were significant independent risk factors that affected overall survival in patients with Siewert type II and III adenocarcinoma of the esophagogastric junction. Conclusions:PG is safe and feasible for patients with Siewert types II and III adenocarcinoma of the esophagogastric junction. The number of lymph nodes dissected and metastasis status were similar in the TG and PG groups.
9.Analysis of the current status and influencing factors of frailty in patients aged 75 and above after percutaneous coronary intervention
Yang CHEN ; Shiyu WANG ; Chuan GAO ; Wenqing CAI ; Yajing SU ; Yumeng ZHANG ; Qingyin LI
Chinese Journal of Nursing 2025;60(13):1588-1595
Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16%.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P<0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P<0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.
10.Effect of UGT8 on colorectal cancer cell proliferation and migration and its correlation with SOX9 expression
Pang YIXIN ; Li WENQING ; Yao QILONG ; Wang YU ; Zhang XIUMEI
Chinese Journal of Clinical Oncology 2025;52(12):595-602
Objective:To investigate the effect of uridine diphosphate ceramide galactosyltransferase 8(UGT8)on colorectal cancer(CRC)cell growth and migration,elucidate an underlying mechanism,and assess the potential regulatory role of SRY-box transcription factor 9(SOX9)on UGT8.Methods:UGT8 and SOX9 mRNA expression levels in CRC tissues,and correlation between their expression levels,were analyzed using GEPIA2,UALCAN,and TIMER 2.0 online databases.UGT8 and SOX9 protein expression in CRC and adjacent tissues was detec-ted using immunohistochemistry,and relationships between their expression and clinicopathological characteristics were analyzed.Impact of UGT8 knockdown on CRC cell proliferation was assessed using a CCK-8 assay,and cell migration was evaluated using Transwell and wound healing assays.Western blot was performed to detect expression of epithelial-mesenchymal transition(EMT)markers(E-cadherin and ZEB1).RT-qPCR and Western blot were used to measure UGT8 mRNA and protein expression levels after SOX9 knockdown.The JASPAR online database was used to assess SOX9 potential for binding to the UGT8 promoter.Results:Bioinformatics analyses revealed significantly higher mRNA expression levels of both UGT8 and SOX9 in CRC tissues than in normal tissues.Positive correlation was observed between expres-sion levels.Immunohistochemistry results showed that tumor UGT8 and SOX9 protein levels were significantly higher than those in adjacent tissues.UGT8 protein level was found to correlates with N stage,and SOX9 protein level correlated with T stage.A positive correlation was observed between UGT8 and SOX9 expression levels.Following UGT8 knockdown,cell proliferation capacity was attenuated and cell migra-tion ability was reduced.E-cadherin expression concurrently increased and ZEB1 expression decreased.RT-qPCR and Western blot results showed that SOX9 knockdown significantly reduced UGT8 mRNA and protein levels.The JASPER website predicts that SOX9 will bind to the UGT8 promoter.Conclusions:UGT8 and SOX9 are highly expressed in CRC tissues,and their expression levels correlate with clinicopatholo-gical features.UGT8 and SOX9 expression levels display significant positive correlation.Mechanistically,UGT8 promotes CRC cell prolifera-tion and migration by facilitating epithelial-mesenchymal transition(EMT).SOX9 enhances UGT8 mRNA and protein expression and may bind to the UGT8 promoter region.

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