1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
2.Retrospective analysis of unexpected antibodies in primary-screened D-negative blood donors
Hecai YANG ; Yin GUAN ; Xiaoli MA ; Yonglei LYU ; Minglu GENG ; Yi CAO ; Liping WANG ; Hongwei MA
Chinese Journal of Blood Transfusion 2025;38(11):1556-1561
Objective: To analyze the frequency and investigate the causes of unexpected antibodies in D-negative blood donors. Methods: From January 2022 to December 2024, 3 768 D-negative blood donors sent to our laboratory were selected as research subjects. D-negative confirmation test and RhCE phenotype detection were applied by saline tube method and microcolumn gel indirect antiglobulin test (IAT), respectively. Antibody screening and identification were performed using the polybrene method and IAT column agglutination methods. Anti-D, anti-C and anti-G specificities were identified by a two-step adsorption-elution method, and the genotypes of D-negative samples were determined by RHD gene amplification, Sanger sequencing, and PacBio Single Molecule Real-Time (SMRT) sequencing. Results: Among D-negative donors, ccee and Ccee phenotypes accounted for the highest proportion, 55.68% (2 098/3 768) and 29.56% (1 114/3 768), respectively, while CcEE and CCEe phenotypes were the least, with one case detected in each, accounting for 0.03% (1/3 768). A total of 165 cases with D variant phenotype were detected, and the proportion of D variant was 4.38% (165/3 768) in the donors detected by D-negative confirmation test. Antibody screening positive blood donors were identified in 93 cases with a proportion of 2.47% (93/3 768). Antibody specificity was determined in 84 blood donors, and 9 samples showed no clear specificity. Anti-D was detected most frequently (n=68), in which 6 of them were detected having multiple antibodies, anti-D + anti-C (n=2), anti-D + anti-G(n=1), and anti-D + anti-E(n=3). The other antibodies detected were anti-E (n=1), anti-M(n=9), anti-P1 (n=3), anti-Le
(n=1), and anti-HI(n=2). Fourteen cases were detected with anti-D in serological D-negative donors with C+ or E+ phenotype, in which three of them were DVI type 3 individuals and 11 cases were D negative individuals. Conclusion: The incidence of unexpected antibodies was higher in D-negative blood donors than in the total donors, with anti-D being the most common. The data provide insights for prevention and monitoring hemolytic disease of the fetus and newborn (HDFN) caused by anti-D. To ensure the safety of blood transfusion, routine unexpected antibody screening for RhD-negative blood donors is recommended to prevent the use of unexpected antibodies positive plasma in the clinic.
3.Interpretation of the China Guidelines for the Prevention and Treatment of Diabetes(2024 Edition)
Jingxia YIN ; Li YU ; Danlan PU ; Xiaoli XU ; Yong LIAO
Journal of Chongqing Medical University 2025;50(5):557-564
In recent years,significant progress has been made in diabetes research both domestically and internationally,new diagno-sis and treatment techniques and methods have been constantly emerging,and clinical research evidence has been continuously accu-mulated and updated.To keep pace with these important developments,the Diabetes Branch of the Chinese Medical Association has ac-tively organized experts to update the China Guidelines for the Prevention and Treatment of Diabetes.This update aims to provide a more comprehensive and scientific guide for diabetes prevention and treatment,greatly promote the standardized and integrated man-agement of diabetes by clinicians,and ensure that patients receive standardized and personalized treatment plans to improve therapeu-tic outcomes and quality of life.
4.Efficacy of interventional therapy for post-pancreaticoduodenectomy hemorrhage and factors influencing rebleeding
Zhengyu JIANG ; Yu YIN ; Jun YANG ; Mingming LI ; Xiaoli ZHU ; Bangjian ZHOU ; Caifang NI
Journal of Interventional Radiology 2025;34(6):639-644
Objective To investigate the DSA imaging characteristics and efficacy of interventional treatment for post-pancreaticoduodenectomy hemorrhage(PPH),and to analyze the factors influencing recurrent bleeding following successful interventional hemostasis.Methods Clinical data of patients who underwent interventional treatment for PPH between January 2013 and December 2022 were retrospectively analyzed.All patients underwent DSA examination,and interventional therapy was the primary treatment option for patients with positive findings.Statistical analysis was performed on DSA angiography manifestations,bleeding sites,success rate of interventional treatment and hemostasis effectiveness.Univariate and multivariate logistic regression analysis were used to analyze the independent risk factors for rebleeding after interventional treatment for PPH.Results A total of 139 patients with PPH were included in this study.All 139 patients underwent DSA examination,with a positive rate of 82.01%(114/139)in the first examination.Major angiographic manifestations included contrast agent extravasation,pseudoaneurysm,and disrupted vascular architecture;bleeding sites included gastroduodenal artery in 45 cases(39.47%),hepatic artery in 22 cases(19.30%),and superior mesenteric artery in 32 cases(28.07%).107 patients underwent interventional treatment(81 embolization and 26 stenting),with a success rate of 91.59%(98/107).The independent risk factors for recurrent bleeding after interventional treatment in patients with PPH included preoperative bleeding(P<0.001)and pancreatic fistula(P=0.041).Conclusion Interventional procedures for PPH can be efficient in diagnosis and treatment,with a high success rate and effective hemostasis.However,it should be noted that some patients remain at risk of recurrent bleeding after successful interventional hemostasis.
5.Clinical Application of NETs in Diagnosis and Monitoring of Acute Ischemic Stroke
Wendi YANG ; Yaxin WANG ; Jing QIAN ; Limin YIN ; Fengting MU ; Xiaoli ZHAO
Journal of Kunming Medical University 2025;46(10):97-105
Objective To explore the value of neutrophil extracellular trapping nets(neutrophil extracellular traps,NETs)in the diagnosis and monitoring of acute ischemic stroke(acute ischemic stroke,AIS).Methods From June 2023 to February 2024,63 patients newly diagnosed with AIS at the Ganmei Hospital Affiliated with Kunming Medical University were selected as the experimental group,and 58 non-AIS individuals matched in gender,age,and other characteristics were selected as the control group.The NETs levels of patients in the experimental group were detected before and 7-10 days after treatment,and general clinical data and related laboratory results were statistically analyzed.Results The experimental group showed significantly higher levels of NEUT,LYMPH,MONO,EO,FDP,D-dimer,and NETs compared to the control group(P<0.05).The NETs levels before treatment were significantly higher than those at 7~10 days after treatment and in the control group(P<0.05).The NETs levels 7~10 days after treatment were significantly higher than those in the control group(P<0.05).NEUT,MONO,FDP,D-dimer,and NIHSS scores were positively correlated with the pre-treatment NETs levels(P<0.05).Elevated serum NETs levels were associated with AIS risk factors(P<0.05).The combined diagnostic value of NEUT,D-dimer,and NETs for AIS was superior to other indicators.Conclusion NETs are highly expressed in the serum of patients with acute ischemic stroke,and serum NETs have certain value in the auxiliary diagnosis and monitoring of acute ischemic stroke.
6.Prognostic value of 18F-FDG PET/CT combined with clinical staging/scoring system in nasal extranodal natural killer/T-cell lymphoma
Yuhu LYU ; Lianglan YIN ; Xiaotian XIA ; Yongxue ZHANG ; Xiaoli LAN ; Chunxia QIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(3):134-140
Objective:To compare and choose the best method for measuring metabolic tumor volume (MTV) of nasal extranodal natural killer/T-cell lymphoma (ENKTL), evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters and clinical staging/scoring systems for patients with nasal ENKTL, and explore the added value of the two combinations for prognostic prediction. Methods:From January 2016 to September 2022, 44 patients (26 males, 18 females; age (47.5±13.6) years) pathologically diagnosed with nasal ENKTL who underwent 18F-FDG PET/CT imaging before treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively collected. SUV 2.5, SUV 4.0 and 41%SUV max were used as thresholds to measure MTV and total lesion glycolysis (TLG), and the consistency was analyzed by Bland-Altman analysis. The ROC curve analysis was used to compare the prognostic efficiency of different methods and determine the best method. The prognostic values of different clinical factors and clinical staging/scoring systems between groups were evaluated by corrected χ2 test. The independent factors were screened by Cox-regression model, and the combined diagnosis model was constructed by logistic regression. Results:Of 44 patients, 6(13.6%) were dead, with the overall survival (OS) of 32.05(11.77, 64.43) months, and the 2-year and 5-year OS rates of 86.6% and 82.5%, respectively. The mortality of different groups in age (≥60 and <60 years), prognostic index of natural killer cell lymphoma (PINK) score (low- and high-risk), and international prognostic index (IPI) score (low- and high-risk) were significantly different ( χ2 values: 5.02, 4.12, 3.88, all P<0.05). The consistency of MTV measured by different thresholds was good. Among them, the MTV measured by threshold of SUV 2.5 had the highest predictive efficiency with the AUC of 0.737. Multivariate analysis showed that MTV (hazard ratio ( HR)=10.488, 95% CI: 1.864-59.026, P=0.008) was the independent influencing factor of OS. By removing other factors, minimization model was obtained, including MTV and PINK score ( P values: 0.006, 0.048). The prediction model of MTV combined with PINK score improved prognostic efficacy with the AUCs of MTV, PINK score and the combination model of 0.781, 0.741 and 0.912, respectively. Conclusions:MTV measured by threshold of SUV 2.5 has better prognostic predictive value. MTV is the independent prognostic factor for OS in nasal ENKTL patients. MTV combined with PINK score has better prognostic value.
7.The application of percutaneous puncture renal fascia suspension in laparoscopic partial nephrectomy
Qi LI ; Pei ZHENG ; Yusheng WANG ; Guangyuan JING ; Mingrui WANG ; Bo ZHAO ; Tengfei XU ; Xiaoli WANG ; Kaidong WANG ; Xiao PAN ; Fen YIN
Chinese Journal of Urology 2024;45(1):53-54
When partial nephrectomy is performed by posterior abdominal approach, the surgical field is poorly exposed, resulting in increased surgical difficulty and risk of injury.In this study, 28 patients with T 1a stage kidney tumors underwent retroperitoneal laparoscopic partial nephrectomy. Intraoperatively, exposure of the surgical field was achieved using the percutaneous puncture of the renal fascia suspension technique. There were no dissatisfactory exposures due to peritoneal damage during the surgery, no additional tubes were inserted, and no conversions to open surgery were needed. The operation time was (76.5±20.3) minutes, blood loss was (92.1±18.7) ml, renal artery clamping time was (19.5±4.3) minutes. Postoperatively, there were no complications such as bleeding, infection, or hematuria.
8.Effect of patent foramen ovale on development of post-operative stroke in patients undergoing non-cardiac surgery: a meta-analysis
Chen CHEN ; Xiaoli YANG ; Xiaotian SUN ; Yunzhi SHEN ; Huiwen JIANG ; Yanhua YIN
Chinese Journal of Anesthesiology 2024;44(3):292-296
Objective:To evaluate the effect of patent foramen ovale on the development of post-operative stroke in the patients undergoing non-cardiac surgery using a meta-analysis approach.Methods:A comprehensive search was conducted across multiple databases including PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, and China Journal Full Text Database.The inclusion criteria encompassed studies assessing the correlation between patent foramen ovale and post-operative stroke.The primary outcome measure focused on the incidence of post-operative stroke, and secondary outcome measures comprised mortality, myocardial infarction rate, and readmission rate within 30 days after surgery. The quality of literature meeting the inclusion criteria was evaluated and data were extracted, and then meta-analysis was conducted using RevMan 5.4 software.Results:Eight retrospective cohort studies involving 21 142 237 patients were included.The results of meta-analysis showed that patent foramen ovale was associated with post-operative stroke and readmission within 30 days after surgery.There were no significant differences in all-cause mortality and myocardial infarction rates between patent foramen ovale group and mon-patent foramen ovale group ( P>0.05). Conclusions:Patent foramen ovale can increase the risk of post-operative stroke in the patients undergoing non-cardiac surgery.
9.Pharmacokinetics and Bioequivalence Study of Generic Tofacitinib Citrate Tablets
Ping LU ; Jie WANG ; Xiaoli YIN ; Shunzhi ZHANG ; Wei WU
Herald of Medicine 2024;43(2):203-207
Objective To assess the pharmacokinetic characteristics of two types of tofacitinib citrate tablets in healthy individuals and evaluate their bioequivalence and safety.Methods A randomized,two-period,self-crossing design was used with 36 subjects in two groups in both fasting and postprandial conditions.Each group received 5 mg tofacatile citrate tablets of either generic tofacitinib citrate tablets(T)or the reference product(R)per period,and the plasma concentration of tofacatile tablets was detected by LC-MS/MS.Phoenix WinNonlin software was used to calculate pharmacokinetic parameters and evaluate its bioequivalence.Results After single oral administration of test and reference preparations,the main pharmacokinetic parameters were as follows:Cmax values in fasting group were(57.54±13.95)and(59.17±12.31)ng·mL-1,respectively;AUC0,values were(143.83±34.58)and(142.13±33.00)ng·h·mL-1,respectively;AUC0-∞ values were(147.39±35.27)and(146.15±34.64)ng·h·mL-1,respectively;tmax was 0.5 h for both;Cmax values in the postprandial group were(57.16±17.56)and(55.19±21.98)ng·mL-1;AUC0-t values were(165.47±41.63)and(162.04±41.84)ng·h·mL-1;AUC0-∞ values were(171.88±44.15)and(168.05±44.21)ng·h·mL-1;The t max was 1.0 h for both.The 90%confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ in fasting group and postprandial group were 96.35%(90.11%-103.03%)and 105.91%(95.20%-117.83%),101.02%(98.76%-103.34%)and 102.23%(99.67%-104.86%),100.77%(98.53%-103.06%)and 102.40%(99.81%-105.06%),all within the range of 80.00%-125.00%.Conclusion Both types of generic tofacitinib citrate tablets are bioequivalent and safe in Chinese healthy individuals.
10.Study on the Construction of a Question-Answer Corpus Dataset for Chinese Medical Knowledge Large Language Models
Tingyu LYU ; Xiaoying LI ; Ying ZHANG ; Yuyang LIU ; Jinhua DU ; Xinyi LI ; Yan LUO ; Xiaoli TANG ; Huiling REN ; Hui LIU ; Hao YIN
Journal of Medical Informatics 2024;45(5):20-25
Purpose/Significance To construct a Chinese medical knowledge Q&A corpus dataset as a standardized evaluation bench-mark for large language models(LLMs)in the medical domain,so as to improve the accuracy and efficiency of LLMs in handling Chinese medical questions.Method/Process Chinese medical paper knowledge,medical terminology explanations and supplementary questions are acquired from the Chinese medical licensing examination,and open-source Chinese medical Q&A datasets are encompassed in the developed Q&A datasets.Result/Conclusion The Chinese medical knowledge Q&A corpus datasets enrich the sources of existing datasets and promote the objective and comprehensive quantitative evaluation of large models in the medical field.In the near future,additional data such as electronic medical records and those from online health communities will be used to strengthen the support of artificial intelli-gence for the Healthy China strategy.

Result Analysis
Print
Save
E-mail