1.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
2.A VBM study on gray matter structure alterations in patients with Alzheimer’s disease comorbid with apathy
Yi JI ; Xuerui PANG ; Chaoyi YANG ; Yulong DAI ; Shanshan ZHOU ; Xingqi WU ; Kai WANG
Acta Universitatis Medicinalis Anhui 2026;61(1):156-162
ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease (AD) comorbid with apathy (AD-A). MethodsThe study included 30 patients with AD-A, 30 AD disease patients without apathy (AD without apathy, AD-NA), and 30 healthy controls (HCs) matched in gender, age, and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) was used to analyze changes in gray matter volume among the three groups. Additionally, the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age, gender, years of education, or total intracranial volume. Compared with the HCs group, both the AD-A and AD-NA groups showed significantly lower scores in cognitive function (P<0.001). The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group (P<0.001). Compared with the AD-NA group, the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus, left orbitofrontal cortex, lingual gyrus, inferior frontal gyrus, superior frontal gyrus, entorhinal cortex, right middle frontal gyrus and posterior cingulate cortex (FWE-corrected, P<0.05 for all). Compared with the HCs group, the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus, left fusiform gyrus, calcarine sulcus, postcentral gyrus, right inferior frontal gyrus and supramarginal gyrus (FWE-corrected, P<0.05 for all). Compared with the HCs group, the AD-NA group showed reduced gray matter volume in the left precuneus, inferior temporal gyrus, and right inferior temporal gyrus (FWE-corrected, P<0.05 for all). In the AD-A group, changes in the gray matter volume of the left caudate nucleus (r= -0.557, P=0.002) and right middle frontal gyrus (r=-0.620, P=0.001) were negatively correlated with the apathy evaluation scale (AES) scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit, and the degree of gray matter atrophy was correlated with the severity of apathy.
3.Correlation of mitochondrial genetic differentiation and spatial variables of Oncomelania hupensis robertsoni in Yunnan Province
Yuanyuan ZHANG ; Jing SONG ; Yuwan HAO ; Zaogai YANG ; Xinping SHI ; Siqi NING ; Hongqiong WANG ; Chunhong DU ; Jihua ZHOU ; Zongya ZHANG ; Kai LI ; Shizhu LI ; Yi DONG
Chinese Journal of Schistosomiasis Control 2026;38(1):54-59
Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.
4.The Dual Role of p21 in Hormone-related Cancers and Its Therapeutic Implications
Jia-Wen LI ; Yang CHEN ; Jia-Qi WANG ; Yu-Kai MA ; Zhi-Yi GUO
Progress in Biochemistry and Biophysics 2026;53(3):593-608
p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.
5.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
6.Historical trend analysis and future projection of osteoarthritis disease burden attributable to high body mass index in China
Ping ZHU ; Ju LI ; Zhongyuan ZHANG ; Jiajia WANG ; Yi′an TIAN ; Rui YUE ; Deqian MENG ; Kai WANG
Chinese Journal of Rheumatology 2025;29(8):662-667
Objective:This study aims to analyze historical trends and predict future trends of disability-adjusted life years (DALYs) attributable to high BMI for osteoarthritis (OA) in China. OA is a common chronic degenerative joint disease, with high body mass index (BMI) being a significant risk factor. in China.Methods:Based on the Global Burden of Disease (GBD) 2021 database, we analyzed trends in high-BMI-attributable OA. The ASR of hogh-BMI-attributable OA DALYs increased from DALYs in China from 1990 to 2021. A Bayesian age-period-cohort (BAPC) model was used to predict trends from 2022 to 2046. Age-standardized rates (ASR) and estimated annual percentage changes (EAPC) were calculated to assess trend changes of trends. A Bayesian age-period-cohort (BAPC) model was used to predict trends from 2022 to 2046. Chi-square tests were used to compare differences in high BMI attribution proportions between regions and years.Results:From 1990 to 2021, China′s OA DALYs increased from 1.829 to 5.327 million, with the proportion attributable to high BMI rising from 13.47% to 21.86% ( χ2=60 527.25, P<0.001). The ASR of high-BMI-attributable to OA increased from 27.4 (-2.2, 81.5) per 100,000 to 53.0 (-4.7, 150.7) per 100 000, with an EAPC of 2.48% [95% (uncertainty interval, UI): 2.35, 2.62]. In 2021, females showed significantly higher ASR (69.2 per 100 000) than males (36.1 per 100 000). Knee OA (ASR: 50.5/100 000) demonstrated substantially higher burden than hip OA (ASR: 2.5/100 000). Age effect analysis showed DALYs peaked at ages 80~90; period effect indicated accelerated growth after 2005; cohort effect showed a U-shaped trend with the 1990 birth cohort having the highest relative risk (approximately 3.0). Projections indicated that up to 2046, total OA DALYs will reach approximately 2.39 million with an ASR of about 71, showing more significant growth among females (ASR reaching 100). Conclusion:High-BMI-attributable to OA DALYs in China shows a significant upward trend, and is expected to continue. This trend is more pronounced among females and elderly populations than males, highlighting the urgency of implementing preventive measures for high-risk groups, particularly in weight management.
7.CNV Encompassing SNP Detection by Cross-reactivity Probe
Xiao-Mei HU ; Chen ZHOU ; Pin-Zheng ZHANG ; Yang CHEN ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):895-902
Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.
8.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
9.Application of real-time virtual sonography combined with intraductal biliary contrast-enhanced ultrasound in percutaneous transhepatic cholangial drainage
Huajun WU ; Jianwei YI ; Zhigang HU ; Binghai ZHOU ; Jiafu GUAN ; Jinlong YAN ; Xin YU ; Rongfa YUAN ; Shubing ZOU ; Kai WANG
Chinese Journal of Surgery 2025;63(8):732-737
Objective:To explore the application value of real-time virtual sonography (RVS) combined with intraductal biliary contrast-enhanced ultrasound (IB-CEUS) in percutaneous transhepatic cholangial drainage (PTCD).Methods:This retrospective cohort study included data from 71 patients who underwent PTCD at the Department of Hepatobiliary and Pancreatic Surgery in the Second Affiliated Hospital of Nanchang University between May 2021 and August 2022. There were 36 male and 35 female patients,aged 35 to 94 years. Based on the guidance modality used,patients were divided into two groups: the RVS combined with IB-CEUS group ( n=36) and the digital subtraction angiography (DSA) group ( n=35). PTCD was performed under the guidance of RVS combined with IB-CEUS in the RVS+IB-CEUS group,and under conventional DSA fluoroscopic guidance in the DSA group. Two clinicians classified the biliary conditions as either simple or complex based on preoperative ultrasound and CT (or MRI) imaging. Statistical analyses were conducted using independent sample t-tests,rank-sum tests, χ2 tests,or Fisher′s exact tests,as appropriate. Results:Significant differences were observed between the RVS+IB-CEUS group and the DSA group in terms of the number of punctures (1.0±0.2 vs. 2.2±1.4, t=-5.148, P<0.01) and postoperative complication rate(2.8% (1/35) vs. 17.1% (6/36), P=0.049). There were 9 patients with complex biliary conditions in the DSA group and 12 in the RVS+IB-CEUS group. The number of punctures in both the simple and complex subgroups of the RVS+IB-CEUS group(1.0±0.2 and 1.0±0.0) remained lower than that in the corresponding DSA subgroups(2.2±1.6 and 2.4±0.4) ( t=-3.606, P<0.01; t=-3.959, P=0.002). Moreover,the complication rate in the simple biliary subgroup of the RVS+IB-CEUS group was significantly lower than that of the DSA group(0 (0/24) vs. 19.2% (5/26), P=0.031),whereas no significant difference was found in the complex biliary subgroup (1/12 vs. 1/9, P=0.686). Conclusion:Guided by RVS and IB-CEUS, PTCD can help reduce the number of punctures during surgery and postoperative complications, and patients with complex bile duct conditions can still benefit from PTCD.
10.The Role of Zinc Finger Structure Transcription Factors ZNF148 and SP5 on P53 Transcriptional Activity
Dai-Wei WANG ; Chen ZHOU ; Pin-Zheng ZHANG ; Xu-Ying WANG ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi YAN ; Zhi-Ting WANG ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):707-715
P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8%)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P<0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1%and 35.7%(P<0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

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