1.PES1 Repression Triggers Ribosomal Biogenesis Impairment and Cellular Senescence Through p53 Pathway Activation
Chang-Jian ZHANG ; Yu-Fang LI ; Feng-Yun WU ; Rui JIN ; Chang NIU ; Qi-Nong YE ; Long CHENG
Progress in Biochemistry and Biophysics 2025;52(7):1853-1865
ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.
2.Correlation between food-specific IgG antibodies and phenotypes of chronic spontaneous urticaria
Xin TONG ; Jian WU ; Liming ZHANG ; Xinghua GAO ; Shi LIAN ; Haiping ZHANG ; Wei ZHU ; Zaipei GUO ; Jingyi LI ; Mengmeng LI ; Li HE ; Xiang NONG ; Xiongming PU ; Shirong YU ; Hongduo CHEN ; Ting XIAO
Chinese Journal of Dermatology 2023;56(2):130-135
Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.
3.Analysis of the new WHO guideline to accelerate the progress towards elimination of schistosomiasis in China.
Zhao Yu GUO ; Jia Xin FENG ; Li Juan ZHANG ; Yi Biao ZHOU ; Jie ZHOU ; Kun YANG ; Yang LIU ; Dan Dan LIN ; Jian Bing LIU ; Yi DONG ; Tian Ping WANG ; Li Yong WEN ; Min Jun JI ; Zhong Dao WU ; Qing Wu JIANG ; Song LIANG ; Jia Gang GUO ; Chun Li CAO ; Jing XU ; Shan LÜ ; Shi Zhu LI ; Xiao Nong ZHOU
Chinese Journal of Schistosomiasis Control 2022;34(3):217-222
On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.
China/epidemiology*
;
Disease Eradication
;
Humans
;
Public Health
;
Schistosomiasis/prevention & control*
;
World Health Organization
4.Urodynamic assessment of bladder storage function after radical hysterectomy for cervical cancer.
Ting-Ting CAO ; Hong-Wu WEN ; Yu-Nong GAO ; Qiu-Bo LYU ; Hui-Xin LIU ; Sha WANG ; Shi-Yan WANG ; Hua-Xin SUN ; Na YU ; Hai-Bo WANG ; Yi LI ; Zhi-Qi WANG ; Olivia H CHANG ; Xiu-Li SUN ; Jian-Liu WANG
Chinese Medical Journal 2020;133(19):2274-2280
BACKGROUND:
After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.
METHODS:
A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.
RESULTS:
Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.
CONCLUSION
A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.
5.Clinical Significance of Common Gene Mutations in 53 Patients with Acute Myeloid Leukemia Harboring 11q23/MLL Rearrangements.
Shu-Xiao BAI ; Yan-Lei GONG ; Jing-Ren ZHANG ; Chun-Xiao WU ; Jun ZHANG ; Hui-Ying QIU ; Hong-Jie SHEN ; Jian-Nong CEN ; Su-Ning CHEN ; Jin-Lan PAN
Journal of Experimental Hematology 2020;28(3):717-723
OBJECTIVE:
To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients.
METHODS:
53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing.
RESULTS:
21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy.
CONCLUSION
A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
Chromosomes, Human, Pair 11
;
Hematopoietic Stem Cell Transplantation
;
Humans
;
In Situ Hybridization, Fluorescence
;
Leukemia, Myeloid, Acute
;
Mutation
;
Prognosis
;
fms-Like Tyrosine Kinase 3
6.HPLC specific chromatogram of Vernonia anthelmintica and determination of six components.
Zong-Yang LIU ; Ke ZAN ; La Maiti Ai-Li SHA ; Xia WU ; Li-Nong GUO ; Shuang-Cheng MA ; Jian ZHENG ; Xiao-Qing CHEN
China Journal of Chinese Materia Medica 2020;45(4):910-915
This work aims to establish an HPLC specific chromatogram and determine six components of Vernonia anthelmintica with chlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, scutellarein and luteolin as index components. HPLC analysis was performed on a Waters Xbridge C_(18) column(4.6 mm×250 mm, 5 μm) with gradient elution of acetonitrile-0.05% trifluoroacetic acid solution at a flow rate of 1.0 mL·min~(-1). The detection wave length was 360 nm and the column temperature was 30 ℃. Chemometrics software Chempattern was employed to analyze the data. HPLC specific chromatogram of V. anthelmintica was established and six characteristic peaks were marked. Six characteristic peaks were simultaneously determined by HPLC within 50 min. The contents of the six components in 13 batch samples of V. anthelmintica were 0.14%-0.68%, 0.44%-0.74%, 0.63%-1.01%, 0.14%-0.71%, 0.15%-0.26% and 0.010%-0.030%, respectively. The HPLC specific chromatogram of V. anthelmintica, together with determination of six components showed strong specificity, and it can be used for the quality control of the crude drug.
Chromatography, High Pressure Liquid
;
Drugs, Chinese Herbal/chemistry*
;
Phytochemicals/analysis*
;
Quality Control
;
Vernonia/chemistry*
7.Current status and transmission risks of oversea imported schistosomiasis in China
Jian-Feng ZHANG ; Li-Yong WEN ; Jing XU ; You-Sheng LIANG ; Xiao-Lan YAN ; Guang-Hui REN ; Tie-Wu JIA ; Wei WANG ; Xiao-Nong ZHOU
Chinese Journal of Schistosomiasis Control 2019;31(1):26-32
With the acceleration of the process of global integration, China’s international exchanges and cooperation with other countries have been further increased. The personnel exchange has led to the frequent occurrence of imported schistosomiasis from abroad, which seriously endangers people’s health. This paper reviews the prevalence and transmission risks of oversea imported schistosomiasis, providing the reference for the entry and exit health quarantine and prevention and control of schistosomiasis in China.
8.An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels.
Ya Zhen QIN ; Li Wen ZHU ; Shang LIN ; Su Xia GENG ; Sheng Wei LIU ; Hui CHENG ; Cheng Ye WU ; Min XIAO ; Xiao Qing LI ; Rui Ping HU ; Li Li WANG ; Hai Yan LIU ; Dao Xin MA ; Tao GUAN ; Yuan Xin YE ; Ting NIU ; Jian Nong CEN ; Li Sha LU ; Li SUN ; Tong Hua YANG ; Yun Gui WANG ; Tao LI ; Yue WANG ; Qing Hua LI ; Xiao Su ZHAO ; Ling Di LI ; Wen Min CHEN ; Ling Yu LONG ; Xiao Jun HUANG
Chinese Journal of Hematology 2019;40(11):889-894
Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
China
;
Core Binding Factor Alpha 2 Subunit
;
Humans
;
Leukemia, Myeloid, Acute
;
RUNX1 Translocation Partner 1 Protein
;
Real-Time Polymerase Chain Reaction
;
Transcription, Genetic
;
WT1 Proteins
9.Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study.
Jian-Qiu WU ; Yong-Ping SONG ; Li-Ping SU ; Ming-Zhi ZHANG ; Wei LI ; Yu HU ; Xiao-Hong ZHANG ; Yu-Huan GAO ; Zuo-Xing NIU ; Ru FENG ; Wei WANG ; Jie-Wen PENG ; Xiao-Lin LI ; Xue-Nong OUYANG ; Chang-Ping WU ; Wei-Jing ZHANG ; Yun ZENG ; Zhen XIAO ; Ying-Min LIANG ; Yong-Zhi ZHUANG ; Ji-Shi WANG ; Zi-Min SUN ; Hai BAI ; Tong-Jian CUI ; Ji-Feng FENG
Chinese Medical Journal 2018;131(15):1767-1775
Background:
Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.
Methods:
A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.
Results:
In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.
Conclusions:
R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.
Trial Registration
ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged
;
Aged, 80 and over
;
Antineoplastic Combined Chemotherapy Protocols
;
therapeutic use
;
China
;
Cyclophosphamide
;
administration & dosage
;
Doxorubicin
;
administration & dosage
;
Female
;
Follow-Up Studies
;
Humans
;
Lymphoma, Follicular
;
drug therapy
;
Lymphoma, Large B-Cell, Diffuse
;
drug therapy
;
Male
;
Middle Aged
;
Prospective Studies
;
Rituximab
;
therapeutic use
;
Vincristine
;
administration & dosage
10.Characterizing the Molecular Abnormalities in Rare Ph Acute Myeloid Leukemia.
Hong-Ying CHAO ; Guang-Ying SHENG ; Xiu-Wen ZHANG ; Min ZHOU ; Hong-Jie SHEN ; Su-Ning CHEN ; Jian-Nong CEN ; Yi-Wu SUN ; Tao CHEN ; Xu-Zhang LU ; Ri ZHANG
Chinese Medical Journal 2018;131(10):1246-1248
Adolescent
;
Adult
;
Female
;
Humans
;
Leukemia, Myeloid, Acute
;
genetics
;
Male
;
Middle Aged
;
Young Adult

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