1.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
2.TCM practitioners’ attitudes and perceptions regarding the use of Ephedra sinica Stapf: An observational study
Aiwen Chang ; Xiaopeng Zhao ; Lin Zhang ; Sijia Zhao ; Zhongyi Pan ; Chenxi Song ; Yanling Fu
Journal of Traditional Chinese Medical Sciences 2024;11(4):435-442
Objective:
To understand the attitudes and perceptions of traditional Chinese medicine (TCM) practitioners in Beijing TCM hospitals regarding the use of Ephedra sinica Stapf (E. sinica, Ma Huang).
Methods:
A two-stage cross-sectional study was conducted using a questionnaire survey of TCM practitioners in Beijing TCM hospitals between April 2023 and March 2024. The questionnaire included demographic information, the clinical background of TCM practitioners, and the clinical application of E. sinica. Logistic regression analysis was used to analyze the relevant influencing factors when using E. sinica.
Results:
Of the 465 questionnaires collected, 441 were valid. Among these, 84.81% (374/441) reported having used E. sinica in clinical practice at least once. The commonly used doses of E. sinica—excluding the pediatric department—were 10 g for high doses, 6 g for medium, and 3 g for low. The three most frequently used formulas for E. sinica included Maxing Shigan decoction, Mahuang decoction, and Xiao Qing Long decoction. The most common TCM patterns treated with a high dose of E. sinica were wind-cold exterior pattern, wind-cold invading the lung, and wind and water combat with meridians congealed by cold. The top three Western medical diagnoses when using E. sinica for treatment were common cold, pneumonia, and upper respiratory tract infections. Nearly half of the respondents reported experiencing adverse reactions from the oral administration of E. sinica, with the most common being palpitations, insomnia, and restlessness. Starting with a low dose and gradually increasing it as appropriate was identified as an effective approach.
Conclusion
This study investigated the attitudes and perceptions of TCM practitioners in Beijing TCM hospitals regarding the dose–efficacy–adverse reaction relationship of E. sinica, providing a reference for the safe and effective clinical use of E. sinica.
3.Development and validation of guardianship ability scale for guardians of patients with severe mental disorders: a study on reliability and validity
Xiaoling DUAN ; Zihua PAN ; Shaoling ZHONG ; Yanling LIANG ; Xiao TAN ; Liang ZHOU
Sichuan Mental Health 2024;37(6):549-556
BackgroundThe guardianship ability of guardians of patients with severe mental disorders plays an important role in supporting the patients' recovery and reintegration into society. It is necessary to develop a scientific tool since there is a lack of tools to quantitatively assess the guardianship ability. ObjectiveTo explore and develop an assessment scale for the guardianship ability of guardians of patients with severe mental disorders, so as to provide references for the construction of scientific and reasonable guardianship ability evaluation tools. MethodsA pool of scale items was constructed through a literature review and interviews, followed by two rounds of expert consultation with 15 specialists. 364 guardians of patients with severe mental disorders in Guangzhou were investigated. The scale items were screened and optimized using item analysis and exploratory factor analysis, and the structural validity of the scale was further verified through confirmatory factor analysis. The content validity of the scale was evaluated by item-level content validity index (I-CVI) the average scale-level content validity index (S-CVI/Ave). The reliability of the scale was tested by Cronbach's α coefficient and split-half reliability. ResultsThe guardianship ability scale for guardians of patients with severe mental disorders consists of 25 items, including three dimensions of guardianship willingness, guardianship knowledge and behavior and guardianship self-efficacy. The results of the item analysis showed that all items met the corresponding criteria and were retained. Validity test: the I-CVI ranged from 0.800 to 1.000, and the S-CVI/Ave was 0.964. Factor load of each item on the corresponding factors ranged from 0.596 to 0.976, and the model demonstrated good fit: chi-square degree of freedom ratio (χ2/df) was 2.444, Tucker-Lewis index (TLI) was 0.908, comparative goodness of fit index (CFI) was 0.917, standardized root mean square residual (SRMR) was 0.049, and root mean square residual (RMSEA) was 0.089. Reliability test showed that the total scale had a Cronbach's α coefficient of 0.966, and the split half reliability coefficient was 0.915. ConclusionThe guardianship ability scale for patients with severe mental disorders developed in this study has good reliability and validity, and has certain application value for the assessment of guardianship ability for patients with severe mental disorders. [Funded by Health Science and Technology Project of Guangzhou (number, 20221A011049)]
4.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
5.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
6.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
7.Construction of endogenous RNA regulatory network for colorectal cancer based on bioinformatics.
Yijie LI ; Feng YUAN ; Zhiren LIN ; Yanling PAN
Journal of Central South University(Medical Sciences) 2022;47(4):416-430
OBJECTIVES:
The high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (circRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. This paper aims to construct a circRNA/miRNA/mRNA regulatory network so as to explore the molecular mechanism of CRC.
METHODS:
The sequencing data of circRNA from CRC were obtained from Gene Expression Omnibus (GEO). The differential circRNA was screened and its structure was identified by Cancer-specific CircRNA Database (CSCD); the sequencing data of miRNA and messenger RNA (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) database and the differentially expressed genes were screened; the corresponding miRNA of differential circRNAs were predicted by CircInteractome database; DIANA, Miranda, PicTar, and TargetScan databases were used to predict the target genes of different miRNAs; the target genes from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched by R language; String database combined with Cytoscape 3.7.2 software was used to construct protein-protein interaction (PPI) network and hub genes were screened; the expressions of mRNAs in the Top10 hub genes were verified in CRC. The network diagrams of circRNAs/miRNAs/mRNAs and circRNAs/miRNAs/Top10 hub mRNAs were constructed by Cytoscape3.7.2. Real-time PCR was used to examine the expression levels of hsa_circRNA_0065173, hsa-mir-450b, hsa-mir-582, adenylate cyclase 5 (ADCY5), muscarinic acetylcholine receptor M2 (CHRM2), cannabinoid receptor 1 (CNR1), and lysophosphatidic acid receptor 1 (LPAR1) in the CRC tissues and the adjacent normal tissues.
RESULTS:
A total of 14 differential circRNAs were identified, and 8 were found in CSCD; 34 miRNAs targeted by circRNAs were obtained. The PPI network was constructed, and the Top10 hub genes were identified, which were CHRM2, melanin concentrating hormone receptor 2 (MCHR2), G-protein gamma 3 subunit (GNG3), neuropeptide Y receptor Y1 (NPY1R), CNR1, LPAR1, ADCY5, adenylate cyclase 2 (ADCY2), gamma 7 (GNG7) and chemokine 12 (CXCL12), respectively. The expressions of Top 10 hub genes were also verified, and the results showed that the Top 10 hub genes were down-regulated in CRC; the constructed network diagram showed that hsa_circRNA_0065173 may regulate ADCY5, CHRM2, and Hsa-mir-450b by modulating hsa-mir-450b and hsa-mir-582. CNR1 and LPAR1 genes might serve as potentially relevant targets for the treatment of CRC. Real-time PCR results showed that the expression levels of hsa_circRNA_0065173, ADCY5, CHRM2, CNR1 and LPAR1 in the CRC tissues were significantly reduced compared with the adjacent normal tissues (all P<0.05); the expression levels of hsa-mir-450b and hsa-miR-582 were significantly increased (both P<0.05).
CONCLUSIONS
In this study, a potential circRNAs/miRNAs/mRNAs network is successfully constructed, which provides a new insight for CRC development mechanism through ceRNA mediated by circRNAs.
Colorectal Neoplasms/genetics*
;
Computational Biology/methods*
;
Gene Regulatory Networks
;
Humans
;
MicroRNAs/genetics*
;
RNA, Circular/genetics*
;
RNA, Messenger/genetics*
8.Effect of information technology-based transitional care on treatment effect of children and adolescents with type 1 diabetes mellitus: a Meta-analysis
Yacong LU ; Yanling MAO ; Huiwen LIU ; Liting PAN ; Bizhen CHEN
Chinese Journal of Modern Nursing 2022;28(6):745-751
Objective:To systematically review the effect of information technology-based transitional care on the treatment effect of children and adolescents with type 1 diabetes mellitus (T1DM) , so as to provide a reliable scientific basis for their out-of-hospital transitional care.Methods:Randomized controlled trial (RCT) of information technology continued nursing intervention for children and adolescents with T1DM in PubMed, Web of Science, CNKI and other databases were searched by computer. The retrieval time was from the establishment of databases to July 31, 2021. According to inclusion and exclusion criteria, literature was screened and data was extracted. Cochrane was used to evaluate the risk of bias for literature quality. Meta-analysis was performed using RevMan 5.4 software, and subgroup analysis was conducted on intervention methods, duration and intervention objects of different ages.Results:Finally, a total of 12 literatures were included, and the quality of literatures was medium. A total of 1 353 cases were included. The results of meta-analysis showed that there were significant differences in the glycated hemoglobin value and the incidence of acute complications between the information technology transitional care group and the traditional nursing group ( P<0.05) . Subgroup analysis showed that different intervention methods (App, Internet platform) and duration of intervention had significant differences in the effect of out-of-hospital treatment for children and adolescents with T1DM ( P<0.05) . Conclusions:The use of information technology-based transitional care can improve out-of-hospital glycosylated hemoglobin value and reduce the incidence of acute complications in children and adolescents with T1DM. Different intervention methods (App, Internet platform) and different intervention time can improve the out-of-hospital treatment effect of children and adolescents with T1DM. It is suggested to promote information technology continuation care in out-of-hospital treatment of children and adolescents with T1DM.
9.Practice of pre-hospitalization in operation department of a hospital in Guangzhou
Hui PAN ; Jianxin YU ; Zhina RU ; Yanling WU ; Bo LIANG ; Huiyan TAN ; Jinkun HUANG
Chinese Journal of Hospital Administration 2021;37(3):229-231
Since the performance appraisal of national tertiary public hospitals was carried out, higher requirements have been put forward for the operation and management of hospitals. Under the premise of ensuring the quality of medical service and medical safety, how to save hospital operating costs and improve the efficiency is an urgent problem for hospital managers. Supported by information upgrading, a tertiary hospital in Guangzhou reformed the treatment process and carried out pre-hospitalization in surgical departments. Data showed that pre-hospitalization can significantly shorten the length of stay, reduce hospitalization costs, and improve the operation efficiency of the hospital.
10.Efficacy observation of Da Vinci robotic-assisted laparoscopic resection for liver benign tumors
Shengzhe LIN ; Ge LI ; Wei PAN ; Jiangzhi CHEN ; Xinran CAI ; Yanling CHEN
Cancer Research and Clinic 2021;33(10):760-762
Objective:To explore the safety and feasibility of Da Vinci robotic-assisted laparoscopic resection in treatment of liver benign tumors.Methods:The clinical data of 62 patients with liver benign tumors admitted to Fujian Medical University Union Hospital from January 2016 to December 2019 were retrospectively analyzed. All patients were divided into 2 groups: 25 cases undergoing Da Vinci robotic-assisted laparoscopic resection (the robotic group) and 37 cases undergoing conventional laparoscopic resection for liver benign tumors (the laparoscopic group). The operation duration, intraoperative blood loss, postoperative abdominal drainage tube removal time, incidence of postoperative complications, postoperative hospital stay time of both groups were compared.Results:Operations of all 62 patients were successfully completed. The operation time of the robotic group was longer than that of the laparoscopic group [(192±52) min vs. (158±41) min], intraoperative blood loss of the robotic group was less than that of the laparoscopic group [(159±67) ml vs.(213±59) ml], and differences were statistically significant between the two groups (both P < 0.05). The postoperative abdominal drainage tube removal time of the robotic group and the laparoscopic group was (7.0±1.5) d and (7.2±1.3) d, the incidence of postoperative complications was 8.0% (2/25) and 5.4% (2/37), and the postoperative hospital stay time was (7.0±2.4) d and (7.3±2.2) d, respectively; and differences were statistically significant between both groups (all P > 0.05). Conclusion:Da Vinci robotic-assisted laparoscopic resection is a safe and effective operation method in treatment of liver benign tumors with advantages of small wound and less blood loss.


Result Analysis
Print
Save
E-mail