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.Clinical trial of tislelizumab combined with chemotherapy in the treatment of patients with stage Ⅲb-Ⅳ non-small cell lung cancer
Xiao-Xue LI ; Yi ZHANG ; Shu-Yang YAO ; Jing-Ying NONG
The Chinese Journal of Clinical Pharmacology 2024;40(3):335-339
Objective To analyze the effect of tislelizumab combined with chemotherapy in the treatment of stage Ⅲb-Ⅳ non-small cell lung cancer(NSCLC)and its influence on T lymphocyte immunity and survival prognosis.Methods Patients with NSCLC were divided into control group and treatment group according to different treatment methods.The control group was treated with platinum-containing dual-drug combined chemotherapy regimen(PC regimen:intravenous drip of pemetrexed 500 mg·m-2 on the 1st day and intravenous drip of carboplatin with area under plasma concentration-time curve(AUC)=5 mg·mL-1·min-1 on the 1st day;TP regimen:intravenous drip of taxol 135 mg·m-2 on the 1st day,and intravenous drip of carboplatin with AUC=5 mg·mL-1·min-1 on the 1st day to 3rd day).The treatment group was given tislelizumab 200 mg intravenously once every 3 weeks on the basis of the control group.Both groups were treated for 2 cycles by taking 3 weeks as 1 treatment cycle.The clinical efficacy,serum tumor markers levels,T lymphocyte immune function,progression-free survival(PFS)and overall survival(OS)and occurrence of adverse drug reactions during treatment were compared between the two groups.Results There were 40 cases in control group and 40 cases in treatment group.After treatment,the total effective rates in control group and treatment group were 40.00%(16 cases/40 cases)and 62.50%(25 cases/40 cases),the disease control rates were 70.00%(28 cases/40 cases)and 90.00%(36 cases/40 cases),carcinoembryonic antigen(CEA)levels were(9.21±2.03)and(5.42±1.36)ng·mL-1,carbohydrate antigen 125(CA125)levels were(72.53±8.16)and(31.95±5.08)U·mL-1,carbohydrate antigen 19-9(CA19-9)levels were(25.79±3.31)and(10.38±2.04)U·mL-1,cytokeratin19 fragment antigen 21-1(CYFRA21-1)levels were(6.47±1.34)and(4.26±0.91)ng·mL-1,CD3+levels were(54.36±5.81)%and(61.85±4.96)%,CD4+levels were(31.28±2.93)%and(43.08±3.15)%,CD4+/CD8+were 1.43±0.40 and 1.91±0.46,survival rates were 47.37%(18 cases/38 cases)and 67.57%(25 cases/37 cases),PFS were 7.73 months(95%CI:6.42-9.03)and 9.75 months(95%CI:8.68-10.82),and OS were 8.96 months(95%CI:7.94-9.97)and 10.52 months(95%CI:9.78-11.27)respectively(all P<0.05).There were no statistically significant differences in the incidence of gastrointestinal reactions,liver dysfunction,bone marrow suppression,hypothyroidism and non-infectious pneumonia between both groups(all P>0.05).Conclusion Tislelizumab combined with chemotherapy has a good effect in the treatment of stage Ⅲb-Ⅳ NSCLC,and it can effectively reduce the levels of serum tumor markers,improve the T lymphocyte immune function,and prolong the survival time of patients,with good safety.
3.Quality evaluation of Fuzheng capsules based on HPLC fingerprint and multi-ingredient content determination
Song CHEN ; Yunrong LI ; Luwei NONG ; Li LI ; Xianzai JIANG ; Cuiqiong ZENG ; Liuping WANG
China Pharmacy 2024;35(22):2726-2731
OBJECTIVE To establish the fingerprint of the Zhuang medicine preparation Fuzheng capsules and a method for the determination of multi-ingredient content for quality evaluation. METHODS High-performance liquid chromatography (HPLC) was used in conjunction with the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine (2004A edition) to establish the fingerprint of 12 batches of Fuzheng capsules, evaluate their similarity and confirm the common peaks. Cluster analysis and principal component analysis were performed using SPSS 20.0 software with the peak areas of the common peaks in the fingerprint as variables. The same HPLC method was adopted to determine the content of liquiritin, specnuezhenide, 3,6′-disinapoyl sucrose and ammonium glycyrrhizinate in the 12 batches of samples. RESULTS A total of 22 common peaks were identified in the fingerprints of the 12 batches of Fuzheng capsules, with the similarities greater than 0.91. Four common peaks were identified as liquiritin (peak 8), specnuezhenide (peak 10), 3,6′-disinapoyl sucrose (peak 11), and ammonium glycyrrhizinate (peak 21). The 12 batches of samples could be clustered into 3 categories, with 200801, 200802 and 200803 as category Ⅰ, samples 1 to 8 as category , and 221101 as category Ⅲ. The sample 200802 had the highest comprehensive score (2.540). The contents of liquiritin, specnuezhenide, 3,6′-disinapoyl sucrose and ammonium glycyrrhizinate in the 12 batches of samples were 0.44 to 0.73, 1.28 to 2.47, 0.08 to 0.12, and 1.31 to 1.81 mg per capsule, respectively. CONCLUSIONS The main components of the 12 batches of Fuzheng capsules were similar, but the content varied, with the sample 200802 indicating the highest quality. The established fingerprint and multi-ingredient content determination method were highly specific and accurate, which can be used for the quality evaluation of Fuzheng capsules in combination with chemical pattern recognition analysis.
4.Compositional Analysis of 11 Nucleosides and Bases in Fritillaria taipaiensis P.Y.Li from Different Origins and the Differences in Their Origin
Chunmei MEI ; Fugui CHEN ; Yuwei ZHAO ; Dan WANG ; Changcan SHI ; Hongkai QIU ; Nong ZHOU ; Weidong LI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):411-418
Objective The contents of 11 nucleosides and base components in 10 batches of samples from 5 provinces(cities)including Chongqing,Yunnan and Shaanxi were determined,and the differences in nucleosides and base components in Fritillaria taipaiensis were compared by chemometric analysis,and the quality was comprehensively evaluated,so as to provide a reference for the cultivation of excellent varieties and the selection of medicinal materials.Methods Nucleoside and base components were extracted from Fritillaria taipaiensis by ultrasonication in aqueous solutions,and the content of each component was determined by HPLC-DAD method.The origin was classified by principal component analysis(PCA)and hierarchical cluster analysis(HCA).Partial least squares discriminant analysis(PLS-DA)was used to determine the differentiated index components in Fritillaria taipaiensis.Then the differences in the contents of the index components among samples from different origins were compared.Results It was found that 11 nucleoside and base components differed significantly among different origins of Fritillaria taipaiensis.Principal component analysis and hierarchical cluster analysis indicated that all samples could be clustered into 4 categories.Five characteristic components,including uracil,cytosine,uridine,inosine,and adenosine,were identified by PLS-DA.The nucleosides and bases in samples from Chongqing and Hubei were relatively high,and the quality of the samples was comparatively superior.Conclusion This method is simple,reproducible,accurate and reliable.It has screened out the index nucleoside and base components in the identification of Fritillaria taipaiensis of different origins,which can be used to initially elucidate the differences of samples between different origins.Additionally,it can better reflect the quality of Fritillaria taipaiensis,and can provide reference for the selection of procurement origin and the quality control for Fritillaria taipaiensis.
5.Analysis of in vivo components and metabolism pathway in rats after intragastric administration of aqueous extract from Abrus cantoniensis
Kuikui CHEN ; Yuxin NONG ; Zhonghui GUO ; Yong TAN ; Hongting HUANG ; Jinman LI ; Jinrui WEI ; Zhiying WEI ; Jie LIANG
China Pharmacy 2024;35(13):1576-1581
OBJECTIVE To analyze the chemical components that were the absorbed in blood and liver tissue of rats after intragastric administration of aqueous extract from Abrus cantoniensis, and to speculate its possible metabolic pathways, providing reference for basic analysis of pharmacological substance in A. cantoniensis. METHODS Male SD rats were randomly divided into A. cantoniensis group (0.63 g/kg, calculated by crude drug) and blank group; they were given relevant drug solution/ultrapure water intragastrically. After a single dose, plasma and liver samples of rats in each group were collected. UPLC-Q-TOF/MS technology was used to identify chemical components that were absorbed in the blood and liver tissue of rats. RESULTS Totally, 30 chemical constituents were identified from the water extracts of A. cantoniensis, including alkaloids, flavonoids, organic acids, iridoids (such as L-abrine, schaftoside, isoshaftoside). Ten prototype components and nine metabolites (such as decarboxylation and sulfation metabolites of protocatechuic acid, reduced sulfated metabolites of p-hydroxybenzoic acid) were identified from plasma samples; six prototype components and five metabolites (such as sulfated metabolites of p-hydroxybenzoic acid, decarboxylation and sulfation metabolites of p-hydroxybenzoic acid) were identified from liver samples. The main metabolic pathways included hydroxylation, demethylation, methylation, sulfation, glucuronidation, etc. CONCLUSIONS Alkaloids, flavonoids and organic acids are the main components of the aqueous extract from A. cantoniensis that are absorbed into the blood and liver, their metabolism mainly involves hydroxylation,demethylation, and sulfation.
6.Using self media platforms to create hospital cultural brands with"micro"characteristics:a case study of a class a tertiary hospital
Binghua PAN ; Kai HUANG ; Baolong LAN ; Ziqian HUANG ; Aiyu NONG ; Lihua LI
Modern Hospital 2024;24(1):30-33,37
The dissemination of culture requires carriers.The construction of hospital characteristic culture and hospital brand culture that highlights hospital characteristics needs to be recognized by medical staff and patients.A good hospital culture is one of the important factors to enhance hospital competitiveness,and can also enhance the hospital's reputation among the pub-lic.As a very common way of information circulation in China,self media and integrated media are rapidly developing and inno-vating in the field of healthcare.Hospitals should actively build their own"micro"cultural platforms.Using self media platforms to tell micro stories,popularize micro knowledge,shoot micro movies,publish micro books,hold micro forums,and micro mu-sic,to enrich patients'cultural lives and create an exclusive hospital culture.
7.Digital medical 3D technology versus traditional 2D technology in the diagnosis and treatment of solid abdominal tumors in children
Changyao WU ; Qianghui LI ; Weimo ZHOU ; Xuefeng LONG ; Lin XU ; Junli QUAN ; Zhenliang NONG ; Shilan LIANG
Chinese Journal of Primary Medicine and Pharmacy 2024;31(3):338-341
Objective:To investigate the value of digital medical 3D technology versus traditional 2D technology in the diagnosis and treatment of solid abdominal tumors in children. Methods:A total of 80 children with solid abdominal tumors who received surgical treatment guided by digital medical 3D technology at Guigang People's Hospital from January 2018 to January 2022 were included in the observation group. An additional 80 children with solid abdominal tumors who received surgical treatment guided by traditional 2D technology at the same hospital from January 2014 to December 2017 were included in the control group. Clinical efficacy was compared between the two groups.Results:The surgical time, intraoperative blood loss, postoperative exhaust time, postoperative hospital stay in the observation group were (111.8 ± 28.9) minutes, (26.8 ± 25.2) mL, (2.2 ± 1.2) days, (7.5 ± 1.4) days, respectively, which were significantly shorter or less than those in the control group [(193.1 ± 66.0) minutes, (86.2 ± 47.0) mL, (3.7 ± 0.9) days, (12.2 ± 3.5) days, t = 7.00, 6.88, 5.87, 7.53, all P < 0.05]. The complete surgical resection rate in the observation group was significantly higher than that in the control group [92.5% (74/80) vs. 81.3% (65/80), χ2 = 4.44, P < 0.05]. The incidence of complications in the observation group was significantly lower than that in the control group [6.3% (5/80) vs. 16.3% (13/80), χ2 = 4.00, P < 0.05]. Conclusion:The utilization of digital medical 3D technology in the surgical treatment of solid abdominal tumors in children can markedly decrease surgical time, reduce intraoperative blood loss, promote postoperative recovery, achieve a high surgical resection rate, and minimize postoperative complications.
8.Analysis of risk factors of pleural effusion after spinal separation
Keyi WANG ; Hao QU ; Wen WANG ; Zhaonong YAO ; Xiaowei ZHOU ; Yuhong YAO ; Hengyuan LI ; Peng LIN ; Xiumao LI ; Xiaobo YAN ; Meng LIU ; Xin HUANG ; Nong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2024;44(3):169-176
Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.

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