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.Learning curve in laparoscopic left lateral hepatic sectionectomy
Sijia BAI ; Ting BI ; Fengyang CHEN ; Chunhui WANG ; Lei HAN ; Yufu TANG ; Jianqiao YE ; Shaojie JIANG ; Wenping ZHOU ; Xiaodong FENG ; Wei ZHANG
Chinese Journal of Hepatobiliary Surgery 2023;29(3):170-175
Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.
3.Clinical efficacy of laparoscopic hepatic caudate lobectomy
Luyuan JIN ; Tianze WANG ; Sijia BAI ; Chunhui WANG ; Ting BI ; Xiaodong FENG ; Wei ZHANG
Chinese Journal of Digestive Surgery 2023;22(S1):23-27
Objective:To investigate the clinical efficacy of laparoscopic hepatic caudate lobectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with hepatic caudate lobe tumor who were admitted to the General Hospital of PLA Northern Theater Command from July 2018 to June 2021 were collected. There were 2 males and 3 females, aged 49(range, 26-55)years. All 5 patients underwent laparoscopic hepatic caudate lobectomy. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using telephone interview or outpatient examination to detect tumor recurrence. The follow-up was up to March 2023. Measurement data with skewed distribution were represented as M(range) and count data were described as absolute numbers. Results:(1) Intraoperative situations. All 5 patients underwent laparoscopic hepatic caudate lobectomy with the left approach, including 3 cases receiving laparoscopic partial resection of hepatic caudate lobe, 1 case receiving laparoscopic partial resection of hepatic caudate lobe+left lateral lobectomy and 1 case receiving laparoscopic partial resection of hepatic caudate lobe+cholecystectomy. Intraoperative hilar occlusion was performed in 3 patients. The operation time and volume of intraoperative blood loss of 5 patients was 240(range, 180-370)minutes and150(range, 100-200)mL, respectively. (2) Postoperative situations. On the first day after surgery, the levels of albumin, alanine aminotransferase, and aspartate aminotransferase in 5 patients was 32.9(range, 29.2-40.3)g/L, 104.09(range, 57.11-1 018.67)U/L, and 67.13(range, 58.00-852.66)U/L, respectively. Three of 5 patients showed no significant changes in prothrombin time (PT) on the first day after surgery, while two patients did not undergo PT test. On the third day after surgery, the visual analogue score of 5 patients was mild pain. Among the 5 patients, 1 case had anal exhaust on the postoperative 1st day, and 4 cases had anal exhaust on the postoperative 2nd day. The time to drainage tube removal for 5 patients was 6(range, 4-10)days. There was no postoperative complication such as bleeding, infection, bile leakage or liver failure in 5 patients. Results of postoperative histopathological examination showed that 2 cases with adenoma, 2 cases with cavernous hemangioma and 1 case with smooth myolipoma. The duration of postoperative hospital stay of 5 patients was 6(range, 5-11)days. (3) Follow-up. All 5 patients were followed up for 22 (range, 19-51)months, and there was no tumor recurrence.Conclusion:It is safe and feasible to selectively carry out laparoscopic hepatic caudate lobectomy by strictly gras-ping the indications.
4.Effects of Different Drying Methods on the Main Components of Forsythia suspensa Flowers
Mengting YANG ; Xiang WANG ; Qian WANG ; Xinguo WANG ; Xiaodong BI ; Liying NIU
China Pharmacy 2021;32(8):921-926
OBJECTIVE:To establish the method for the content det ermination of 4 components in Forsythia suspensa flowers by drying in shade ,vacuum freeze-drying ,oven(30,50,70 ℃)and sun ,so as to evaluate the effects of different drying methods on the main components of F. suspensa flowers and screen the optimal drying method. METHODS :UPLC method was adopted. The determination was performed on Waters ACQUITY UPLC BEH C 18 column with mobile phase consisted of acetonitrile- 0.1% phosphoric acid aqueous solution (gradient elution )at the flow rate of 0.3 mL/min. The detection wavelength was set at 230 nm, and column was 35 ℃. The sample size was 1 μL. Euclidean closeness(C)i of different drying methods was calculated by TOPSIS comprehensive analysis method ,and the optimal drying method was defined. RESULTS :The linear range of forsythiaside A , rutin,forsythin,(+)-pinoresinol-4-O-β-D-glucopyranoside were 0.007 5-0.037 7,0.027 4-0.137 2,0.001 9-0.009 5,0.005 6-0.028 8 µg(all r>0.999). RSDs of precision ,stability(32 h)and reproducibility tests were all lower than 2%. The recoveries were 97.27%-102.53%,100.53%-104.11%,98.45%-104.02%,98.66%-104.82%,respectively;and all RSDs <3%(n=3). The contents were 1.645 8-4.987 9,11.730 2-20.978 0,0.875 5-2.005 0,2.366 0-5.535 7 mg/g. The content of forsythiaside A was the highest after drying at 30 ℃,rutin and (+)-pinoresinol-4- O-β-D-glucopyranoside were the highest after vacuum freeze-drying,forsythiaside was the highest after drying at 50 ℃ . Results of TOPSIS analysis showed that Ci of F. suspensa flowers by drying in shade ,vacuum freeze-drying ,oven(30,50,70 ℃)and sun were 0.079 9,0.553 5,0.495 4, 0.503 8,0.157 9,0.217 2,respectively;the order of Ci was vacuum freeze-drying > 50 ℃ oven drying > 30 ℃ oven drying>sun drying >70 ℃ oven drying > shade drying. CONCLUSIONS:Established method is simple ,reproducible and can be used for the content determination of 4 components in F. suspensa flowers. The samples are preferably dried by vacuum freeze-drying,followed by 50 ℃ oven drying ,30 ℃ oven drying , and then dried in the sun and oven at 70 ℃ and finally in the shade.
5.The effect of bulk electron density on the dose accuracy of treatment planning for postoperative cervical cancer
Sheng HAN ; Xiaodong PENG ; Ke YUAN ; Rutie YIN ; Xiongfei LIAO ; Xianliang WANG ; Lei ZHANG ; Min LIU ; Bin BI ; Yazheng CHEN
Chinese Journal of Radiological Medicine and Protection 2021;41(2):140-145
Objective:To study the impact on dose accuracy for the treatment planning by manually assigning accurate electron density for CT image-based tumor tissues and organs at risk.Methods:Twenty cases of retrospective postoperative cervical cancer radiotherapy plans were selected. The body electron density of the corresponding organs was derived from the ICRU 46 report and assigned in the treatment planning system (Monaco5.11, Sweden), including the bladder, rectum, intestine, kidney, spinal cord, femoral head, and ilium. The original plans were double-arc volumetric modulated arc therapy plan (360° VMAT), using Monte Carlo algorithm, the calculation grid was 0.3 cm × 0.3 cm × 0.3 cm, and the minimum subfield width was 0.6 cm. Keep the original plan fluence unchanged and recalculate the dose to generate a new plan. The two-dimensional dose distribution and dose-volume histogram (DVH) were used to compare the differences between the two plans. The difference was compared between the two group plans by using the dosimetry parameters and DVH two dimension curve.Results:For the planning of assigning bulk electron density (Plan RED), the deviation of the patient′s target dose parameters and the original plan (Plan ref) was <2%, and the average deviation of all target regions D2, D98, Dmean was < 0.7%, only 2 of the 180 data were between 2% and 3%. The average deviation of V20, V30, D1 cm 3, Dmean of the bladder, rectum, and small intestine, the original Plan ref was less than 0.6%, and 4 out of 240 data had values > 2%. Plan RED′s average hop count was 0.9% higher than Plan ref, and the total number of subfields remains unchanged. The planned dose generated by manually assigning the electron density in Plan RED was higher than that in Plan ref, but met the clinical requirements. The two-dimensional curves of the DVH diagram for targets and OARs almost completely overlapped, and there was no obvious difference in the dose distribution diagram of the same cross section. The statistical result of all parameters showed that the difference in planned dose parameters between the two groups was not statistically significant( P>0.05). Conclusions:The overall deviation of dose accuracy between Plan RED and Plan ref is <2%, which meets the clinical requirements and provides a reference for realizing MRI-only treatment planning.
6.Effect analysis of the library diversified information source-based system construction for improving medical students' information literacy
Lijun TIAN ; Wei BI ; Lihua GUO ; Xiaodong WANG
Chinese Journal of Medical Education Research 2021;20(8):919-921
This research aims at the existing problems of medical students' information literacy to cultivate medical students' information literacy through the construction of cloud libraries, medical school characteristic library, medical schools sharing electronic resources and the establishment of medical student information literacy competitions. The results show that the total scores of medical students' information awareness, information knowledge, information ability, information ethics and information literacy have been greatly improved after the teaching reform [(11.56±1.37) vs. (15.64±1.88), (10.28±1.33) vs. (16.50±1.64), (9.50±1.29) vs. (15.22±1.90), (10.04±1.23) vs. (14.81±1.57), (41.92±3.20) vs. (61.59±3.57)], with statistical significance ( P<0.001). The medical significance shows that the teaching reform based on the construction of the library's diversified information source system can significantly improve the information literacy level of medical students.
7. Association between the JAG2 gene polymorphism and the occurrence of nonsyndromic cleft lip with or without cleft palate in northwest Chinese population
Jie LEI ; Xi SHEN ; Boshi BI ; Sixuan ZHAO ; Ruimin LIU ; Xiaodong XIE
Chinese Journal of Medical Genetics 2020;37(1):75-79
Objective:
To assess the association of
8.Effect of sufentanil on apoptosis in spinal cord neurons of mice with peripheral nerve injury
Tingting JI ; Xizhe ZHANG ; Qi ZHOU ; Jiannan SONG ; Jian CAO ; Xiaodong LIANG ; Haibo LI ; Liwei BI ; Yi SUN
Chinese Journal of Anesthesiology 2019;39(3):331-334
Objective To evaluate the effect of sufentanil on apoptosis in spinal cord neurons of mice with peripheral nerve injury. Methods One hundred and fifty clean-grade healthy male BALB∕c mice, aged 6-8 weeks, weighing 18-22 g, were divided into 3 groups ( n=50 each) using a random number table method: sham operation group (group Sham), peripheral nerve injury group (group PNI) and sufentanil group ( group SF) . The model of unilateral sciatic nerve injury was established in PNI and SF groups. After establishing the model, sufentanil 5. 0 μg∕kg was intraperitoneally injected once a day for 3 consecutive days in group SF, while the equal volume of normal saline was given instead of sufentanil in Sham and PNI groups. Five mice in each group were sacrificed at days 1, 3, 7, 14 and 28 after surgery ( T0-4 ) , and L4-6 segments of the injure ipsilateral spinal cord were removed for examination of pathological changes ( with a light microscope) and for determination of neuronal apoptosis ( by TUNEL assay) . The ap-optosis index ( AI) was calculated. Five mice in each group were sacrificed at T0-4 , and L4-6 segments of the injured ipsilateral spinal cord were removed for detection of the expression of Bcl-2, Bax and cleaved caspase-3 by Western blot. The ratio of Bcl-2 expression to Bax expression ( Bcl-2∕Bax ratio) was calculat-ed. Results Compared with group Sham, the AI was significantly increased, the expression of Bcl-2 pro-tein was down-regulated, and the expression of cleaved caspase-3 and Bax was up-regulated in PNI and SF groups ( P<0. 05) . Compared with group PNI, the AI was significantly decreased, the expression of Bcl-2 protein was up-regulated, the expression of cleaved caspase-3 and Bax was down-regulated, the Bcl-2∕Bax ratio was increased (P<0. 05), and the pathological changes were significantly attenuated in group SF. Conclusion Sufentanil can inhibit apoptosis in spinal cord neurons of mice with peripheral nerve injury.
9.Cognitive status of Chinese acne patients and its influencing factors
Shuyun YANG ; Ying TU ; Jianting YANG ; Rong JIN ; Yanni GUO ; Xinyu LIN ; Ying QIU ; Hongxia LIU ; Yao XIE ; Yuzhen LI ; Leihong XIANG ; Bo YU ; Xianyu ZENG ; Changchun XU ; Fengyan LU ; Xing LI ; Hua DU ; Xiangfei LIN ; Yuedong QIU ; Feifei ZHU ; Yufu FANG ; Mingfen LYU ; Ruina ZHANG ; Xinlin HU ; Linjun JIAO ; Hongxia FENG ; Xiaodong BI ; Min ZHANG ; Biwen LIN ; Qiao LIU ; Yonghong LU ; Li HE
Chinese Journal of Medical Aesthetics and Cosmetology 2019;25(5):403-410
Objective To indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65%,69.16% and 65.49% of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72%,42.40% and 18.25% of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P<0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P<0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value <0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.
10.Effect of sufentanil on activation of spinal astrocytes in a mice model of single peripheral nerve injury
Haibo LI ; Xizhe ZHANG ; Qi ZHOU ; Jian CAO ; Xiaodong LIANG ; Tingting JI ; Liwei BI ; Yi SUN
The Journal of Clinical Anesthesiology 2017;33(3):294-297
Objective To investigate the effects of sufentanil on activation of spinal astrocytes in mice after unilateral sciatic nerve injury.Methods Eighty healthy male BALB/c mice,aged 6-8 weeks,weighing 18-22 g,were randomly divided into 4 groups (n=20 each): sufentanil high dose group (group H),middle dose group (group M),low dose group (group L) and model group (group MO).After model of sciatic nerve injury was established by unilateral sciatic nerve transection,group H,M and L,sufentanil 10 μg/kg,5 μg/kg,2.5 μg/kg was injected intraperitoneally once a day continuously for 3 days,while the equal volume of saline was injected in group MO.Five mice in each group were selected,and the sciatic nerve functional index were measured at 4,8,12 weeks.The 5 mice were sacrificed from each group and the damage on the same side L4-L6 segments of the spinal cord were removed at 2,4,8,12 weeks.The pathological changes were examined under light microscope at 8 week point.The expression of GFAP was determinatied at each time points by immuno-histochemistry.Results Compared with group L and MO,sciatic nerve functional index significantly was increased in groups H and M (P<0.05),and no significantly change was found in group L.Spinal cord neurons had a better morphology in groups H and M than in group L and MO.Compared with group MO,The expression of GFAP were significantly up-regulated in groups H,M and L (P<0.05).Compared with group L,the expression of GFAP were significantly up-regulated in groups H and M (P<0.05).Conclusion Sufentanil promotes spinal astrocyte activation after peripheral nerve injury in mice and improves repair after peripheral nerve injury.

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