1.Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer
Yue GE ; Sheng MA ; Qiang ZHOU ; Zezhong XIONG ; Yanan WANG ; Le LI ; Zheng CHAO ; Junbiao ZHANG ; Tengfei LI ; Zixi WU ; Yuan GAO ; Guanyu QU ; Zirui XI ; Bo LIU ; Xi WU ; Zhihua WANG
Chinese Medical Journal 2024;137(15):1844-1856
Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.
2.To Explore the Effect of Yifei Jianpi Prescription on Airway Mucus Hypersecretion in COPD Model Rats Based on EGFR/MAPK/MUC5AC Pathway
Yanan ZHANG ; Yuxin ZHANG ; Lili ZHENG ; Sheng WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(8):1115-1122
Objective To explore the therapeutic effects and mechanism of Yifei Jianpi Prescription on airway mucus hypersecretion in chronic obstructive pulmonary disease(COPD)rats through the epidermal growth factor receptor/mitogen-activated protein kinase/mucin 5AC(EGFR/MAPK/MUC5AC)pathway.Methods Male SD rats were randomly divided into blank group,model group,ambroxol group and Yifei Jianpi Prescription low-,medium-and high-dose groups.The COPD rat model with lung and spleen deficiency was replicated by smoking combined with lipopolysaccharide instillation and administration of Folium Sennae.Alcian blue-periodic acid-Schiff staining(AB-PAS)was used to observe bronchial mucus secretion and the degree of goblet cell hyperplasia in rats.Hematoxylin-eosin staining(HE)was used to observe the pathological morphology of lung tissue of rats.Western Blot was used to detect the expression of MUC5AC,EGFR protein,c-Jun N-terminal kinase(JNK),p38 MAPK,protein and phosphorylated protein of extracellular regulated protein kinase(ERK)in rat lung tissues.Real-time fluorescence quantitative PCR(RT-qPCR)was used to detect the mRNA expression of EGFR,JNK,p38 MAPK,MUC5AC,and ERK in rat lung tissues.Results AB-PAS staining showed that the number of goblet cells decreased significantly in ambroxol group and all dose groups of Yifei Jianpi Prescription.HE staining showed that ambroxol group and Yifei Jianpi high-dose group significantly improved the pathological injury of lung tissue.Compared with the blank group,the mRNA expressions of ERK,MUC5AC,p38 MAPK,JNK and EGFR were significantly increased in the lung tissues of the model group(P<0.01),and the expression of MUC5AC and EGFR protein,as well as p38 MAPK,JNK,ERK total and phosphorylated protein were significantly increased(P<0.01).Compared with model group,the protein expression levels of ambroxol group and Yifei Jianpi Prescription medium-and high-dose groups were significantly decreased(P<0.01,P<0.05),while the protein expression levels of EGFR,p38 MAPK and p-p38 MAPK in Yifei Jianpi Prescription low-dose group were decreased(P<0.01,P<0.05).The mRNA expression of EGFR,ERK,JNK,p38 MAPK and MUC5AC in Yifei Jianpi Prescription high-dose and ambroxol groups were decreased(P<0.01,P<0.05),and the mRNA expression of MUC5AC in medium-and low-dose groups were decreased(P<0.05).Conclusion Yifei Jianpi Prescription can reduce the expression of MUC5AC and improve hypersecretion of airway mucus.Its mechanism is related to the EGFR/MAPK signaling pathway.
3.Research progress in 2023 ASCO-GU prostate cancer
Zheng CHAO ; Yanan WANG ; Yue GE ; Qiang ZHOU ; Zezhong XIONG ; Sheng MA ; Junbiao ZHANG ; Le LI ; Zhihua WANG
Journal of Modern Urology 2023;28(6):536-540
The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium unveiled numerous research advances which provide meaningful insights into the selection of treatment regimens of prostate cancer. Precision multi-treatment based on patients’ characteristics has become the predominant approach, including the use of a three-drug combination therapy for metastatic hormone-sensitive prostate cancer, and poly adenosine diphosphate ribose polymerase inhibitor therapy for metastatic castration-resistant prostate cancer. Nuclear medicine therapy and radiotherapy are also receiving significant attention. Integrated nuclear medicine diagnosis and therapy show immense potential for non-metastatic castration-resistant prostate cancer. Additionally, for localized prostate cancer, stereotactic body radiotherapy is a preferred alternative to surgery. This article sheds light on several key studies presented at the conference, focuses on prostate cancer treatment at different stages, and intends to enhance the therapeutic outcome for prostate cancer patients.
4.(+)/(-)-Yanhusamides A-C, three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo.
Lingyan WANG ; Guiyang XIA ; Huan XIA ; Xiaohong WEI ; Yanan WANG ; Sheng LIN
Acta Pharmaceutica Sinica B 2023;13(2):754-764
A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids, (+)/(-)-yanhusamides A-C ( 1- 3), featuring an unprecedented 3,8-diazatricylco[5.2.2.02,6]undecane-8,10-diene bridged system. Their structures were exhaustively characterized by X-ray diffraction, comprehensive spectroscopic data analysis, and computational methods. Guided by the hypothetical biosynthetic pathway for 1- 3, a gram-scale biomimetic synthesis of (±)- 1 was achieved in 3 steps using photoenolization/Diels-Alder (PEDA) [4+2] cycloaddition. Compounds 1‒3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages. The in vivo assay showed that oral administration of 30 mg/kg of (±)- 1 attenuated the severity of rat adjuvant-induced arthritis (AIA). Additionally, (±)- 1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.
5.Dermatomyositis with kidney neoplasm: two cases report and literature review
Sheng MA ; Yue GE ; Zezhong XIONG ; Yanan WANG ; Le LI ; Zheng CHAO ; Beining LI ; Junbiao ZHANG ; Yang LUAN ; Bolin WU ; Gan YU ; Cong LI ; Xing ZENG ; Chunguang YANG ; Zhihua WANG
Chinese Journal of Urology 2023;44(3):200-203
Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.
6.Comprehensive analysis of RNA-seq and whole genome sequencing data reveals no evidence for SARS-CoV-2 integrating into host genome.
Yu-Sheng CHEN ; Shuaiyao LU ; Bing ZHANG ; Tingfu DU ; Wen-Jie LI ; Meng LEI ; Yanan ZHOU ; Yong ZHANG ; Penghui LIU ; Yong-Qiao SUN ; Yong-Liang ZHAO ; Ying YANG ; Xiaozhong PENG ; Yun-Gui YANG
Protein & Cell 2022;13(5):379-385
7.Application of PBL combined with EBM teaching mode in the standardized residency training: a systematic review
Yanan CHEN ; Xiaolan RUAN ; Yangwen OU ; Ziying QIU ; Mengting HUANG ; Liyue ZHANG ; Shixi XIONG ; Sheng LI
Chinese Journal of Medical Education Research 2022;21(6):722-726
Objective:To systematically review the teaching effect of problem-based learning (PBL) combined with evidence-based medicine (EBM) teaching mode on the standardized residency training.Methods:CNKI, Wanfang database, VIP database, SinoMed, Embase, PubMed and Web of SCI databases were searched, and the randomized controlled trial (RCT) studies of the application of EBM combined with PBL teaching in standardized residency training were collected. The retrieval time was from the establishment to 1st July, 2018. Two investigators independently extracted data and assessed the quality of the studies. After assessing the risk of bias of included studies, Meta-analysis was performed on RevMan 5.3.Results:In total, 4 studies were included in the review. Narrative assessment was adopted, because outcome indicators of these study were varied and the quality of the literatures could not meet the requirement of Meta-analysis. Our study suggested that the residents who were in PBL combined with EBM teaching mode group got higher scores in the standardized residency training, compared with those in the lecture-based learning (LBL) teaching mode group, especially in case analysis score, total score of examination, improvement of clinical thinking ability, communication and expression ability, organization and cooperation ability, etc.Conclusion:The current evidence suggests that the application of EBM combined with PBL teaching mode has a positive effect on the standardized residency training. Compared with the traditional LBL teaching, EBM can improve students' ability. However, limited by the quantity and quality of included studies, the above conclusions still need to be verified by more studies with larger samples and higher quality.
8. Analysis of influencing factors for rapid postoperative recovery of young lung cancer patients
Yanan SONG ; Yu QI ; Chunyang ZHANG ; Yinliang SHENG ; Song ZHAO
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(1):17-21
Objective:
To explore the influencing factors of rapid postoperative recovery in young(≤40 years old) lung cancer patients.
Methods:
Retrospective analysis was performed on 82 young patients with lung cancer diagnosed by postoperative pathology admitted to the department of thoracic surgery of the first affiliated hospital of Zhengzhou University from March 2013 to March 2019, the patients were divided into two groups according to their postoperative hospitalization time(hospitalization time≤7d, hospitalization time >7d). The preoperative medical history and examination data, intraoperative(operative method, embedding materials), postoperative complications and postoperative treatment and other data of the enrolled patients were collected to analyze the relationship between various factors and postoperative hospitalization time.Univariate analysis used
9.Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.
Dandan LUO ; Weihong GE ; Xiao HU ; Chen LI ; Chia-Ming LEE ; Liqiang ZHOU ; Zhourui WU ; Juehua YU ; Sheng LIN ; Jing YU ; Wei XU ; Lei CHEN ; Chong ZHANG ; Kun JIANG ; Xingfei ZHU ; Haotian LI ; Xinpei GAO ; Yanan GENG ; Bo JING ; Zhen WANG ; Changhong ZHENG ; Rongrong ZHU ; Qiao YAN ; Quan LIN ; Keqiang YE ; Yi E SUN ; Liming CHENG
Protein & Cell 2019;10(8):566-582
The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.
10.New point variation of DOCK8 gene in hyper IgE syndrome
Xuefeng XU ; Yuanjian SHENG ; Xiaofen TAO ; Yanan SHAO ; Lanfang TANG ; Zhimin CHEN
Chinese Journal of Pediatrics 2019;57(3):227-229

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