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.Effects of Questionnaire-Based Psychological Survey Methods on the Evaluation Results in a Patient Cohort
Yueyao XU ; Wenwen CHEN ; Ling LI ; Li YUAN ; Mengxian HUANG ; Yuanyuan QU ; Huan SONG ; Jianwei ZHU
Acta Academiae Medicinae Sinicae 2024;46(3):324-328
Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group(n=270)or the self-administered group(n=262)to complete the generalized anxiety disorder(GAD-7)and the patient health questionnaire(PHQ-9)scales.The total scores and prevalence rates of anxiety and depres-sion were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups(all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group(P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression(P<0.001,P=0.002).The prevalence rates of moderate to se-vere anxiety(GAD-7 ≥10)and depression(PHQ-9 ≥10)showed no statistically significant difference between the two groups(P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.
3.Establishment of a phase Ⅱ remote home-based cardiac rehabilitation program for patients with coronary heart disease after percutaneous coronary intervention based on social cognitive theory
Ling DAI ; Jianwei ZHOU ; Mingxiang ZHENG ; Lanfang PENG
Journal of Clinical Medicine in Practice 2024;28(22):110-114
Objective To establish a phase Ⅱ remote home-based cardiac rehabilitation (HBCR) program for patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI) based on social cognitive theory (SCT). Methods A preliminary draft of the phase Ⅱ HBCR program for CHD patients after PCI based on SCT was developed through evidence-based literature review and group discussion, and the final version was formed through Delphi expert consultation. Results A total of 18 experts participated in three rounds of expert consultation. The expert authority coefficients for the three rounds were 0.86, 0.87 and 0.87 respectively, and the Kendall's W coefficients were 0.211, 0.242 and 0.271 respectively, with significant differences (
4.Expert consensus on nucleic acid amplification test of respiratory pathogens in children
Zhengde XIE ; Jikui DENG ; Lili REN ; Yan ZHANG ; Xiangpeng CHEN ; Hailin ZHANG ; Linqing ZHAO ; Baoping XU ; Lili ZHONG ; Qiang QIN ; Gen LU ; Yuejie ZHENG ; Deyu ZHAO ; Yunxiao SHANG ; Ling CAO ; Zhimin CHEN ; Yong YIN ; Hanmin LIU ; Adong SHEN ; Binwu YING ; Zhou FU ; Changchong LI ; Yuan QIAN ; Wenbo XU ; Jianwei WANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(5):321-332
Acute respiratory tract infection is the most common infectious disease in children, which seriously threatens children′s health.Rapid and accurate etiological diagnosis is of great significance for the clinical treatment and control of these diseases.Pathogen nucleic acid test was applied and became the main method of respiratory tract infection diagnosis for its high sensitivity and specificity.To regulate the application of pathogen nucleic acid amplification test in respiratory tract infection in children, improve the diagnosis level, expert consensus on nucleic acid amplification test of respiratory pathogens in children was prepared to guide the application and promote pathogens diagnosis ability.
5.The influence of childhood trauma on internet addiction of adolescents: mediating effect of self-concealment
Hua CAO ; Zhijun WANG ; Ling YANG ; Manyu ZHAO ; Ruiqi ZHANG ; Jianwei LIU
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(9):811-816
Objective:To investigate the influence of childhood traumatic experience on internet addiction of adolescents and the mediating effect of self-concealment.Methods:Childhood trauma questionnaire(CTQ), self-concealment scale(SCS) and adolescent pathological internet use scale(APIUS) were used to investigate 532 college students.SPSS 22.0 was used for descriptive statistics, correlation analysis and regression analysis.Amos 24.0 was used for confirmatory factor analysis, and the relevant assumptions were verified through structural equation model.Results:The total scores of childhood abuse, self-concealment and adolescent pathological internet use were (37.23±11.91), (26.09±9.26) and (82.15±28.09), respectively.Correlation analysis showed that childhood trauma was positively correlated with self-concealment ( r=0.27, P<0.01). Self-concealment was positively correlated with internet addiction ( r=0.47, P<0.01). Childhood trauma was positively correlated with internet addiction ( r=0.36, P<0.01). Mediating effect test showed that childhood trauma had a significant positive predictive effect on self-concealment ( β=0.34, P<0.01), self-concealment had a significant positive predictive effect on internet addiction ( β=0.34, P<0.01), and childhood trauma had a direct predictive effect on internet addiction ( β=0.31, P<0.01). Conclusion:Childhood trauma and self-concealment have significant influence on internet addiction, and self-concealment plays a partial mediating role between childhood trauma and internet addiction of adolescents.
6.Safety and efficacy of sacral neuromodulation therapy for lower urinary tract dysfunction in elderly people: A multicenter study
Xiaodong LIU ; Jiawen WANG ; Lingfeng MENG ; Wei ZHANG ; Guanghui DU ; Qing LING ; Xiaodong ZHANG ; Peng ZHANG ; Zhongqing WEI ; Baixin SHEN ; Limin LIAO ; Guoqing CHEN ; Hong SHEN ; Deyi LUO ; Zhihui XU ; Jianwei LYU ; Jiayi LI ; Tie ZHONG ; Qi CHEN ; Wei WEN ; Yaoguang ZHANG
Chinese Journal of Geriatrics 2020;39(4):418-423
Objective:To investigate the safety and efficacy of sacral neuromodulation(SNM)therapy for the treatment of lower urinary tract dysfunction(LUTD)in elderly patients.Methods:Clinical data of 91 elderly patients with LUTD from multiple medical institutions who received SNM during the period from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into four groups: the interstitial cystitis(IC)group(n=28), the neurogenic bladder(NB)group(n=36), the overactive bladder syndrome(OAB)group(n=13)and the idiopathic dysuria(ID)group(n=14). Different sets of evaluation parameters were used for different diseases.Patients’ baseline data and data in stage I(test phase)and stage Ⅱ(permanent SNM)were recorded, statistically analyzed and compared.Results:Ninety-one people underwent SNM treatment.Of them, 53 patients received permanent implants(stage Ⅱ), and the total conversion rate of stage I to stage Ⅱ was 58.2%(53/91). Patients receiving permanent implants(stage Ⅱ)had a preoperative period ranging from 3 months to 30 years, and were followed up for 2 to 58 months after treatment, with an average follow-up of 19.6 months.The improvement rates in stage I for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 35.4%, 31.6%, 33.7%, 32.6%, 49.2%, 43.2% and 13.2%, respectively.The improvement rates in stage Ⅱ for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 43.2%, 40.0%, 37.8%, 50.5%, 70.5%, 70.4% and 43.2%, respectively.Three adverse events occurred, including 1 case of recurrent symptoms, 1 case of moderate infection, and 1 case of electrical lead dislocation.Conclusions:Sacral nerve stimulation has definitive and consistent curative effects on LUTD in elderly people.The follow-up time should be extended to further study the safety of sacral nerve stimulation.
7.Correlation between the distribution of intracranial and extracranial aterial lesions and risk factors in Chinese patients with ischemic stroke :a multicenter registry study
Yu TANG ; Lingyun JIA ; Yingqi XING ; Pinjing HUI ; Xuan MENG ; Delin YU ; Xiaofang PAN ; Yalan FANG ; Binbin SONG ; Chunxia WU ; Chunmei ZHANG ; Xiufang SUI ; Youhe JIN ; Jingfen ZHANG ; Jianwei LI ; Ling WANG ; Yuming MU ; Jingxin ZHONG ; Yuhong ZHU ; Heng ZHANG ; Xiaoyu CAI ; Yang HUA
Chinese Journal of Ultrasonography 2019;28(5):369-374
Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P <0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P <0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P < 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P <0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR= 2 .012 ,1 .637 , 1 .325 ,respectively ;all P <0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR = 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P <0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .
8.Therapeutic effects of endoscopic ultrasound-guided holmium laser ablation for pancreatic primary implantation carcinoma in nude mice
Ling XING ; Jianwei ZHU ; Dong WANG ; Hongyu WU ; Xiaolan ZHANG ; Zhendong JIN ; Bing HU
Chinese Journal of Digestive Endoscopy 2019;36(5):350-354
Objective To explore the effectiveness of endoscopic ultrasound( EUS)-guided holmium laser ablation for primary pancreatic implantation tumor in nude mice. Methods Pancreatic cancer cell line SW1990 were implanted into 204-6-week-old male balb/c nude mice to establish primary pancreatic implantation tumor in situ models. Then the nude mice were randomly divided into two groups, the treatment group(n=10) and the control group(n=10). The treatment group underwent EUS-guided holmium laser ablation in the pancreatic tumor. And no interventions were given to the control group. The volume of tumors of the two groups were measured under EUS at time points of 7 d, 14 d and 28 d after ablation. The activities, appetites and psychosis of all nude mice were evaluated in the meantime. At 28 d after ablation, lesions of pancreas were dissected and sliced for H&E staining. Results There were no complications in the treatment group, and all nude mice could tolerate the procedure. The mental state, activities and appetites of nude mice in the experimental group were better than those in the control group. Tumors of the control group enlarged. There was significant difference in the tumor size between the two groups at 28 d after ablation. HE staining showed coagulation necrosis in the ablation area. Conclusion EUS-guided holmium laser, producing coagulative necrosis in the ablation area, is effective for primary pancreatic implantation carcinoma in nude mice for about 28 days.
9. Effect of enterostomy on analgesic pattern in patients with advanced digestive tract cancer
Jiayu LING ; Yanhong LI ; Lixing ZHONG ; Weiwei LI ; Hao LIU ; Yue CAI ; Huabin HU ; Jianwei ZHANG ; Yanhong DENG
Chinese Journal of Gastrointestinal Surgery 2019;22(12):1159-1164
Objective:
To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer.
Methods:
A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ2 test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of
10.Effect of enterostomy on analgesic pattern in patients with advanced digestive tract cancer
Jiayu LING ; Yanhong LI ; Lixing ZHONG ; Weiwei LI ; Hao LIU ; Yue CAI ; Huabin HU ; Jianwei ZHANG ; Yanhong DENG
Chinese Journal of Gastrointestinal Surgery 2019;22(12):1159-1164
[Abstrect] Objective To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat?sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat?sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non?stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory (BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long?acting opioids were administered, which included sustained?release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ2 test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non?stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two?tailed test was established as the alpha significance level. Result A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty?two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non?stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non?stoma group located in other sites. Compared with non?stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non?stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non?stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)]( χ2=10.023, P=0.002) in the non?stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI:0.102?0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709?18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non?stoma group (49.3%, 35/71) (χ2=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123?0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033?6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.


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