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.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.
3.Current Situation of the Talent Team Construction in the Information Departments of Public Hospitals of Traditional Chinese Medicine in Guangxi
Shan LING ; Qingjiao NONG ; Guozhang HUANG ; Chaoyun LI ; Long CHENG ; Jie ZHANG
Journal of Medical Informatics 2024;45(11):67-71
Purpose/Significance The present situation of the talent team construction in the information departments of public hospi-tals of traditional Chinese medicine(TCM)in Guangxi is analyzed to provide references for optimizing the talent team construction in this field.Method/Process Taking the personnel in the information departments of secondary and above public TCM hospitals in Guangxi in 2022 as the research objects,statistical methods such as Wilcoxon rank sum test,x2 test and Spearman correlation analysis are used to an-alyze the distribution of the research objects and discuss the existing problems in talent team construction.Result/Conclusion The aver-age number of personnel in the information departments of secondary and above public TCM hospitals in Guangxi is 4.39,accounting for 0.80%of the total number of employees.The overall quantity is insufficient,and the distribution is uneven among regions and hospital levels.The talent structure of tertiary TCM hospitals is relatively better than that of secondary TCM hospitals.
4.A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors.
Rong Rui LIU ; Shan Zhi GU ; Tie ZHOU ; Li Zhu LIN ; Wei Chang CHEN ; Dian Sheng ZHONG ; Tian Shu LIU ; Nong YANG ; Lin SHEN ; Si Ying XU ; Ni LU ; Yun ZHANG ; Zhao Long GONG ; Jian Ming XU
Chinese Journal of Oncology 2023;45(10):898-903
Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans
;
East Asian People
;
Neoplasms/pathology*
;
Antibodies, Monoclonal, Humanized/therapeutic use*
5.Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study.
Long Yang ZHU ; Qing LI ; Lu Yao YU ; Ying LIU ; Yi Nong CHEN ; Zhe WANG ; Shi Yu ZHANG ; Jing LI ; Ying LIU ; Yu Lan ZHAO ; Yang XI ; Lin PI ; Yi Hong SUN
Chinese Journal of Cardiology 2023;51(7):731-741
Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.
Humans
;
Atrial Fibrillation/drug therapy*
;
Platelet Aggregation Inhibitors/adverse effects*
;
Acute Coronary Syndrome/drug therapy*
;
Fibrinolytic Agents/therapeutic use*
;
Retrospective Studies
;
Treatment Outcome
;
Anticoagulants
;
Myocardial Infarction/complications*
;
Hemorrhage
;
Percutaneous Coronary Intervention
;
Ischemic Stroke/drug therapy*
;
Stroke
6.A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors.
Rong Rui LIU ; Shan Zhi GU ; Tie ZHOU ; Li Zhu LIN ; Wei Chang CHEN ; Dian Sheng ZHONG ; Tian Shu LIU ; Nong YANG ; Lin SHEN ; Si Ying XU ; Ni LU ; Yun ZHANG ; Zhao Long GONG ; Jian Ming XU
Chinese Journal of Oncology 2023;45(10):898-903
Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans
;
East Asian People
;
Neoplasms/pathology*
;
Antibodies, Monoclonal, Humanized/therapeutic use*
7.Progress of schistosomiasis control in People’s Republic of China in 2021
Li-juan ZHANG ; Zhi-min XU ; Fan YANG ; Jun-yi HE ; Hui DANG ; Yin-long LI ; Chun-li CAO ; Jing XU ; Shi-zhu LI ; Xiao-nong ZHOU
Chinese Journal of Schistosomiasis Control 2022;34(4):329-336
This report presented the endemic status of schistosomiasis and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance sites in the People’s Republic of China at a national level in 2021. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2021. A total of 451 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2021, with 27 571 endemic villages covering 73 250 600 people at risk of infections. Among the 451 endemic counties (cities, districts), 75.17% (339/451), 22.17% (100/451) and 2.66% (12/451) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2021, 29 037 cases with advanced schistosomiasis were documented in China. In 2021, 4 405 056 individuals received serological tests and 72 937 were sero-positive. A total of 220 629 individuals received stool examinations and 3 were positive. In 2021, snail survey was performed in 19 291 endemic villages in China and Oncomelania snails were found in 7 026 villages, accounting for 36.42% of all surveyed villages, with 12 villages identified with emerging snail habitats. Snail survey was performed at an area of 686 574.46 hm2 and 191 159.91 hm2 snail habitats were found, including 1 063.08 hm2 emerging snail habitats and 5 113.87 hm2 reemerging snail habitats. In 2021, 525 878 bovines were raised in the schistosomiasis endemic areas of China, and 115 437 received serological examinations, with 231 positives detected. Among the 128 719 bovines received stool examinations, no positives were identified. In 2021, there were 19 927 schistosomiasis patients receiving praziquantel chemotherapy, and 729 113 person-time individuals and 256 913 herd-time bovines were given expanded chemotherapy. In 2021, snail control with chemicals was performed in 117 372.74 hm2 snail habitats, and the actual area of chemical treatment was 65 640.50 hm2, while environmental improvements were performed in snail habitats covering an area of 1 244.25 hm2. Data from the national schistosomiasis surveillance sites of China showed that the mean prevalence of Schistosoma japonicum infections were both zero in humans and bovines in 2021, and no S. japonicum infection was detected in snails. The results demonstrate that the overall endemic status of schistosomiasis remained at a low level in China in 2021; however, the progress towards schistosomiasis elimination was slowed and the areas of snail habitats rebounded mildly. Strengthening researches on snail diffusion and control, and improving schistosomiasis surveillance and forecast are recommended to prevent reemerging schistosomiasis.
8.Preventive strategy of economy class syndrome.
Xin Nong LIU ; Tong ZHANG ; Yu Long JIA
Chinese Journal of Preventive Medicine 2022;56(8):1150-1153
Economy class syndrome (ECS) refers to a series of symptoms, such as lower limb swelling, chest pain, dyspnea, and sudden death, that occur during or after a long-distance flight. Its essence is venous thromboembolism. ECS, as a preventable syndrome, is one of the causes of sudden death in long-distance travelers. Medical assistance to the African region is a very important diplomatic matter of China. It often takes medical workers more than 10 hours of long-distance flight to reach the recipient country. Therefore, it is essential to improve the understanding of ECS and corresponding prevention strategies among the long-distance traveling people including medical workers assisting Africa, which could guarantee their health and ensure the smooth implementation of the work of assisting Africa.
Africa
;
China
;
Death, Sudden
;
Humans
;
Syndrome
;
Travel
9.Endemic status of schistosomiasis in People’s Republic of China in 2020
Li-Juan ZHANG ; Zhi-Min XU ; Fan YANG ; Hui DANG ; Yin-Long LI ; Shan LÜ ; Chun-Li CAO ; Jing XU ; Shi-Zhu LI ; Xiao-Nong ZHOU
Chinese Journal of Schistosomiasis Control 2021;33(3):225-233
This report presented the endemic status of schistosomiasis in the People’s Republic of China at a national level in 2020, and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2020. A total of 450 counties (cites, districts) were found to be endemic for schistosomiasis in China, with 28 376 endemic villages covering 71 370 400 people at risk of infections. Among the 450 endemic counties (cities, districts), 74.89% (337/450), 21.87% (98/450) and 3.33% (15/450) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2020, 29 517 cases with advanced schistosomiasis were documented in China. In 2020, 11 117 655 individuals received inquiry examinations and 1 798 580 were positive; 5 263 082 individuals received serological tests and 83 179 were sero-positive. A total of 273 712 individuals received stool examinations and 3 were positive, including one case of acute schistosomiasis. In 2020, snail survey was performed in 19 733 endemic villages in China and Oncomelania snails were found in 7 309 villages, accounting for 37.04% of all surveyed villages, with 15 villages identified with emerging snail habitats. Snail survey covered an area of 736 984.13 hm2 and 206 125.22 hm2 snail habitats were found, including 1 174.67 hm2 emerging snail habitats and 1.96 hm2 habitats with infected snails. In 2020, 544 424 bovines were raised in the schistosomiasis-endemic areas of China, and 147 887 received serological examinations, with 326 positives detected, while 130 673 bovines received stool examinations, with no positives identified. In 2020, there were 19 214 patients with schistosomiasis receiving praziquantel chemotherapy, and 964 103 person-time individuals and 266 280 herd-time bovines were given expanded chemotherapy. In 2020, molluscicide treatment was performed in 136 141.92 hm2 snail habitats, and the actual area of chemical treatment was 71 980.22 hm2, while environmental improvements were performed in snail habitats covering an area of 1 464.03 hm2. Data from the national schistosomiasis surveillance sites of China showed that the mean prevalence of Schistosoma japonicum infections were both zero in humans and bovines in 2020, and no S. japonicum infection was detected in snails. The results demonstrate that the overall endemic status of schistosomiasis remains at a low level in China and the goal of the National Thirteenth Five-Year Plan for Schistosomiasis Control was achieved as scheduled; however, the endemic situation of schistosomiasis rebounded in local areas. Precision schistosomiasis control and intensified monitoring of the endemic situation and transmission risk of schistosomiasis are required to be performed to facilitate the progress towards elimination of schistosomiasis steadily.
10.Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China
Shan LÜ ; Chao LÜ ; Yin-Long LI ; Jing XU ; Qing-Biao HONG ; Jie ZHOU ; Jian-Feng ZHANG ; Li-Yong WEN ; Jian-Feng ZHANG ; Shing-Qing ZHANG ; Dan-Dan LIN ; Jian-Bing LIU ; Guang-Hui REN ; Yi DONG ; Yang LIU ; Kun YANG ; Zhi-Hua JIANG ; Zhuo-Hui DENG ; Yan-Jun JIN ; Han-Guo XIE ; Yi-Biao ZHOU ; Tian-Ping WANG ; Yi-Wen LIU ; Hong-Qing ZHU ; Chun-Li CAO ; Shi-Zhu LI ; Xiao-Nong ZHOU
Chinese Journal of Schistosomiasis Control 2021;33(1):10-14
Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

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