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.Short-term outcome study on cervical deep lymph node-venous anastomosis technique in the treatment of Alzheimer’s disease
Cheng GAN ; Zhengdong KONG ; Xiaoye RAN ; Shudong QIAO ; Yixin ZHANG ; Lu YUE ; Yingjie WANG ; Hui BI ; Dong YANG ; Hongtong MA ; Yuan CHEN ; Hongli CHAI ; Ying JIA ; Chenhao MA ; Zixiang CHEN ; Ke LI ; Miao WANG ; Liguo XUE ; Siwen ZHAO ; Ke WEN ; Lin YIN ; Bo DING ; Shan ZHU ; Yuanbo LIU ; Mengqing ZANG
Chinese Journal of Plastic Surgery 2025;41(2):130-143
Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.
3.Short-term outcome study on cervical deep lymph node-venous anastomosis technique in the treatment of Alzheimer’s disease
Cheng GAN ; Zhengdong KONG ; Xiaoye RAN ; Shudong QIAO ; Yixin ZHANG ; Lu YUE ; Yingjie WANG ; Hui BI ; Dong YANG ; Hongtong MA ; Yuan CHEN ; Hongli CHAI ; Ying JIA ; Chenhao MA ; Zixiang CHEN ; Ke LI ; Miao WANG ; Liguo XUE ; Siwen ZHAO ; Ke WEN ; Lin YIN ; Bo DING ; Shan ZHU ; Yuanbo LIU ; Mengqing ZANG
Chinese Journal of Plastic Surgery 2025;41(2):130-143
Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.
4.Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients
Yanru DU ; Jia LI ; Shaoxiang LI ; Chunyan GUAN ; Hongli LI ; Zifen GAO ; Xue LI ; Gehong DONG
Chinese Journal of Hematology 2024;45(1):94-97
To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.
5.Preparation and identification of humanized monoclonal antibody against periostin
Xuejiao LI ; Hang ZHAO ; Shuo ZHANG ; Huiying KANG ; Yannan ZHOU ; Shuang JIA ; Xu LU ; Hongli ZHAO ; Yang HAI
Chinese Journal of Immunology 2024;40(12):2628-2633
Objective:To prepare a humanized monoclonal antibody against periostin and establish a stable cell line.Meth-ods:Based on anti-periostin mouse monoclonal antibody developed by our laboratory,total RNA was extracted,and variable region sequences were obtained by RT-PCR amplification of VH and VL genes.The mouse antibody CDR region was transplanted into the human antibody framework receptor region,and the gene was subcloned into the expression vector PATX-GS2,and stably transfected into CHO cells.Monoclonal cell lines were obtained by MSX pressure screening and limited dilution.Results:VH and VL genes were amplified by RT-PCR,and the sequence of the light and heavy chain variable region were determined.Antibody humanization were successfully stablished by CDR transplantation method a murine antibody to a human framework,and a eukaryotic expression plasmid was constructed,which was transfected into CHO cells for expression,and human anti-periostin antibody was successfully obtained.ELISA and Western blot results showed that the humanized antibody had good anti-periostin activities and binding affinity.Conclu-sion:In this study,anti-periostin humanized monoclonal antibody has been successfully prepared,which can specifically bind to peri-ostin proteins in vivo and have biological activity,providing scientific data for the precise treatment of retinal fibrosis,tissue and organ fibrosis,and malignant tumors.
6.Study on Association between Serum BMP2,BMP7 Level and Left Ventricular Hypertrophy among Chronic Kidney Disease Patients
Honghong JIA ; Hongli LI ; Lihua SUN
Journal of Modern Laboratory Medicine 2024;39(6):179-184
Objective To explore the expression of serum bone morphogenetic protein 2(BMP2),bone morphogenetic protein 7(BMP7)level and its association with left ventricular hypertrophy(LVH)among patients with chronic kidney disease(CKD).Methods A total of 93 CKD patients admitted to Yan'an People's Hospital from June 2019 to June 2023 were collected as CKD group,divided into LVH group(n=34)and non-LVH group(n=59)according to whether concurrence was combined with LVH.A total of 60 healthy volunteers were selected as control group in the same period.The clinical data were collected and serum BMP2 and BMP7 levels were detected by enzyme-linked immunosorbent assay(ELISA).The association between serum BMP2,BMP7 and CKD stage was analyzed by Spearman's rank correlation analysis.Logistic regression analyze was performed to analyze the influencing factors of CKD patients with concomitant LVH.ROC curves were plotted to assess the diagnostic value of serum BMP2,BMP7 on LVH.Results Serum BMP2(106.09±19.34 pg/ml)in CKD group was higher than that in control group(83.76±15.27 pg/ml),and serum BMP7(15.16±4.92 pg/ml)in CKD group was lower than that in control group(26.53±5.80 pg/ml),the differences were statistically significant(t=7.559,13.002,all P<0.05).Serum BMP2 was sequentially increased in patients with CKD stages Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ(90.32±6.04,98.56±6.63,110.32±7.49,121.13±7.82,131.81±7.97 pg/ml),and serum BMP7 was sequentially decreased (20.06±2.79,17.01±2.22,13.34±2.18,11.20±2.01,9.35±2.09 pg/ml),and the differences were statistically significant(F=19.863,11.567,all P<0.05).Serum BMP2 was positively correlated with CKD stage(r=0.592,P<0.05),while serum BMP7 was negatively correlated with CKD stage(r=-0.603,P<0.05).BMP2 was an independent risk factor for LVH in CKD patients[OR(95%CI):1.640(1.317~2.043),P<0.05].BMP7 was a protective factor for LVH in CKD patients[OR(95%CI):0.521(0.349~0.779),P<0.05].Both serum BMP2 and BMP7 had diagnostic value for LVH with AUC(95%CI)of 0.782(0.719~0.832)and 0.791(0.726~0.859),respectively.The AUC(95%CI)of the combination of two indicators was 0.873(0.812~0.930),which was greater than that of single indicator(Z=2.357,2.027,all P<0.05).Conclusion BMP2 is abnormally elevated and BMP7 is abnormally decreased in CKD patients,and the abnormal expression of two indicators is associated with CKD disease and LVH.Early combined detection of two indexes can be used as an indicator for diagnosing LVH.
7.Development of a homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction
Weihui JIA ; Feng CHEN ; Hua ZHONG ; Chonggao YIN ; Hongli LI
Chinese Journal of Medical Education Research 2024;23(2):266-270
Objective:To develop a homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction.Methods:The preliminary contents of the assessment system were determined through a literature review and expert interviews, and two rounds of questionnaire-based consultation was conducted with 20 experts using the Delphi method. With the use of Excel 2016 and SPSS 26.0, we calculated the coefficient of judgement basis (Ca), the coefficient of familiarity (Cs), the coefficient of authority (Cr), and Kendall's coefficient of concordance ( W ) as well as the mean, standard deviation, and coefficient of variation of all parameters, to identify the specific items and weights for the homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction. Results:In the two rounds of consultation, experts were both 100.00% active in responding to the questionnaires; the coefficients of authority of experts were 0.889 and 0.935, respectively; the coefficients of familiarity were 0.856 and 0.936, respectively; the coefficients of judgment were 0.922 and 0.934, respectively; and Kendall's coefficients of concordance were 0.476 and 0.563, respectively. Finally, 7 first-level items and 21 second-level items were included in the content framework of the homogeneous management evaluation system.Conclusions:The construction process of the homogeneous management evaluation system of clinical observership teaching is complete and reliable, which can provide a reference for the homogeneous management of clinical observership teaching, but further verification and improvement are needed.
8.Characteristics of whole blood donors from 26 blood stations before and after the outbreak of COVID-19:a multicenter study
Peng LI ; Youhua SHEN ; Wei GAO ; Wei ZHANG ; Jianling ZHONG ; Hao LI ; Lin BAO ; Ying WANG ; Xuefang FENG ; Tao SUN ; Xiaoqin CHEN ; Li LI ; Hongzhi JIA ; Shouguang XU ; Xiaobo CAI ; Wen ZHANG ; Qunying LAI ; Zhiqiang YU ; Zhenxing WANG ; Yanjun ZHOU ; Peng WANG ; Yanhua ZHANG ; Guoqiang ZHANG ; Haiying NIU ; Hongli JING
Chinese Journal of Blood Transfusion 2023;36(10):907-912
【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.
9.Research Progress of Pharmacological Therapy and Nutritional Support for Cachexia in Lung Cancer Patients.
Jiemin WANG ; Weihui JIA ; Danyang LI ; Yanmei SONG ; Ningxin SUN ; Ke YANG ; Hongli LI ; Chonggao YIN
Chinese Journal of Lung Cancer 2022;25(6):420-424
Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
.
Cachexia/therapy*
;
Combined Modality Therapy
;
Humans
;
Lung Neoplasms/drug therapy*
;
Neoplasms/complications*
;
Nutritional Support/adverse effects*
;
Quality of Life
10.Detection and evaluation of the signals of amlodipine and lercanidipine based on FAERS database
Guizun ZHONG ; Ni ZHANG ; Hongli WANG ; Siqi CHEN ; Li GONG ; Lingyun PAN ; Yuntao JIA
China Pharmacy 2022;33(21):2647-2653
OBJECTIVE To detect and evaluate the signals of amlodipine and lercanidipine -induced adverse drug events (ADE). METHODS All ADE reports about “amlodipine”and“lercanidipine”were searched from FAERS database during Jan . 1st,2004 to Sept . 30th,2021. Reported odds ratio and Bayesian confidence propagation neural network were used to detect ADE signals. The moderately strong signals and strong signals in key systems were selected for analysis . RESULTS From FAERS database,249 657 and 10 558 reports were extracted with amlodipine and lercanidipine as suspect drugs ,respectively. In this study,62 and 58 signals related to amlodipine and lercanidipine were detected respectively . At the same time ,moderately strong signals of peripheral edema , hypotension, orthostatic hypotension and hypovolemic shock were detected in the twodrugs,all of which were common adverse reactions of the two drugs. The special ADEs detected in this study were as follows: in the respiratory system , chest and mediastinaldisease system ,strong signals of non -cardiogenic pulmonary edema were detected for amlodipine ,and strong signals of dyspnea at rest for lercanidipine ;in gastrointestinal diseases ,strong signals of gingival hypertrophy were detected only for amlodipine;in skin and subcutaneous tissue disease system ,moderately strong signals related to “vasculitis”were detected for both drugs,moderately strong signals related to linear IgA disease were detected for amlodipine ,and moderately strong signals related to bullous dermatitis were detected for lercanidipine ;in the renal and urinary system disease system ,the signals of acute renal injury were detected for both drugs (amlodipine was detected as a moderately strong signal ,and lecardipine was detected as a strong signal ); in the mental system ,moderately strong signals related to suicide were detected for amlodipine . Both hypotension and acute renal injury ranked in the top two in the number of reports of the two drugs . The time scan results of the information component (IC)of this study showed that the IC values of non -cardiogenic pulmonary edema and suicide completion signals of amlodipine increased from 0.76,-0.49 to 4.48 and 1.95 respectively,and the confidence intervals narrowed from (-0.44,1.97),(-1.01,0.03)to (4.24,4.72)and(1.90,2.01)respectively during 2004 to 2021,suggesting that the signals kept stable . CONCLUSIONS The risks of peripheral edema ,hypotension,arrhythmia,pulmonary edema ,gingival hyperplasia ,skin related ADE ,acute renal injury , depression and suicide should be alert when using amlodipine and lercanidipine in clinic .

Result Analysis
Print
Save
E-mail