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.Comparison of interobserver variations in delineation of target volumes and organs-at-risk for intensity-modulated radiotherapy of nasopharyngeal carcinoma among physicians from different levels of cancer centers
Meining CHEN ; Yimei LIU ; Yinglin PENG ; Qiuying XIE ; Jinping SHI ; Rong HUANG ; Chong ZHAO ; Xiaowu DENG ; Meijuan ZHOU
Chinese Journal of Medical Physics 2024;41(3):265-272
Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.
3.Application of intraoperative ultrasound in robot-assisted precise resection of pancreatic tumors
Zheng LI ; Wensheng LIU ; Qifeng ZHUO ; Yihua SHI ; Shunrong JI ; Xianjun YU ; Xiaowu XU
Chinese Journal of General Surgery 2024;33(9):1368-1376
The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.
4.Minimally invasive enucleation for benign and low-grade malignant pancreatic tumors: an analysis of 60 cases
Mengqi LIU ; Wensheng LIU ; Zheng LI ; Qifeng ZHUO ; Shunrong JI ; Wenyan XU ; Yihua SHI ; Xianjun YU ; Xiaowu XU
Chinese Journal of Surgery 2022;60(7):674-679
Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.
5.Minimally invasive enucleation for benign and low-grade malignant pancreatic tumors: an analysis of 60 cases
Mengqi LIU ; Wensheng LIU ; Zheng LI ; Qifeng ZHUO ; Shunrong JI ; Wenyan XU ; Yihua SHI ; Xianjun YU ; Xiaowu XU
Chinese Journal of Surgery 2022;60(7):674-679
Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.
6.Analysis of the risk factors influencing the prognosis of patients with recurrent hepatocellular carcinoma after liver transplantation within Fudan criteria and summary of relevant clinical experience
Yifeng HE ; Kang SONG ; Guohuan YANG ; Qiman SUN ; Jian SUN ; Yongsheng XIAO ; Zheng WANG ; Guoming SHI ; Yinghong SHI ; Xiaowu HUANG ; Jia FAN ; Jian ZHOU
Chinese Journal of Organ Transplantation 2021;42(2):82-86
Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.
7.Establishment of Application Database for Electrocardiograph in Different Scenes.
Yajun SHI ; Xiaowu SONG ; Ling GAO ; Ying DONG ; Qing DAN ; Jinli WANG ; Yundai CHEN
Chinese Journal of Medical Instrumentation 2020;44(2):132-135
It is significant to establish scene ECG database which improves the automatic diagnostic function of electrocardiograph under different application scenarios. We built the ECG database in different scene according to the hospital level (grade 3, grade 2, grade 1) and clinical environment (intensive care and acute wards, outpatient clinics and general wards). Sample size was obtained according to the incidence of various ECG diagnoses. The database covers ECG signal, ECG waveform, ECG characteristic values, ECG diagnostic results by experts and clinical information of patients etc. It not only provides important reference for electrocardiograph manufacturers to evaluate and test the parameters of automatic diagnosis under different clinical scene, but also provides valuable scientific research and teaching resources for medical workers.
Databases, Factual
;
Electrocardiography
;
Humans
8.Clinical efficacy of plastic surgery and wound healing to repair the wounds of chest wall tuberculosis
Xiaowu LYU ; Yajie ZHANG ; Shengjuan FENG ; Yuanyuan ZHANG ; Yujia WU ; Pengcheng LI ; Bing SHI ; Zhen LIU ; Chiyu JIA
Chinese Journal of Medical Aesthetics and Cosmetology 2016;22(6):345-347
Objective To treat complex wounds of the chest wall tuberculosis by the use of wound healing techniques (focal debridement + the VSD) and joint plastic surgery (transfer of skin flap, skin graft, flap stuffing, etc) and to explore the clinical features of the tuberculous chest wound, the feasibility and effectiveness of treatments.Methods Clinical data of 11 hospitalized patients with chest wall tuberculosis were collected during 2012-2014.The therapeutic effect, intraoperative and postoperative complications, and postoperative follow-up were retrospectively analyzed.Results Among 7 cases using lesion debridement, VSD suction drainage and local flap repair (skin grafting), 6 cases were cured.The response rate was 90.9%.All 4 cases using debridement and local flap repair (skin grafting) were cured.Only one case of recurrence was observed during the follow-up period of 3-34 months.Conclusions Using of wound healing techniques with plastic surgery is an effective treatment, which has good therapeutic effect on the wound deeply infiltrated.
9.Clinical application of self-expandable metallic stent implantation through bronchoscope in the patients with malignant airway stenosis
Yi HU ; Su ZHAO ; Yang XIAO ; Zhaowu TAO ; Xiaowu SHI ; Wen YIN
Clinical Medicine of China 2014;30(12):1321-1324
Objective To evaluate the short and long term efficacy of self-expandable metallic stent implantation through bronchoscope in the management of the patients with malignant airway stenosis.Methods Seventy-four hospitalized patients with malignant airway stenosis during a 10-year period were selected as our subjects from Dec.2002 to Nov.2012 in the Respiratory Department of the Central Hospital of Wuhan.All these patients underwent bronchoscope for nitinol self-expandable metallic stent implantation.Clinical improvement,6min walking distance (6MWT),mMRC index,arterial blood gas,as well as early and late postoperative complications were investigated.Results A total of 77 stents were implanted,including 34 covered metallic stents and 43 uncovered metallic stents.All patients showed the obvious relief of dyspnea after the operation.6MWT at pre-operation was (172 ± 45)m and (288 ± 36)m at 28 week post-operation.Arterial blood gas was (61.34 ±6.44)mmHg at pre-opemtion and (72.12 ±6.87) mmHg at 28 week post-operation.mMRC was 3.56 ± 0.44 at pre-operation and 1.96 ± 0.37 at 28 week post-operation.All these differences were significant(P < 0.01).The operation succeeded in releasing bucking of patients with esophago-tracheal fistula.Symptoms such as fever,cough,pharyngodynia,foreign body sensation and hemoptysis were observed,and all the above side effect could be solved while no serious complications arose.Conclusion Bronchoscopic insertion of metallic airway stents for malignant airway stenosis is a safe and effective procedure that could obviously relieve respiratory distress and improve the quality of life.
10.Accuracy study of different registration methods for cone beam CT and planning CT in image-guided radiation therapy
Botian HUANG ; Xiaowu DENG ; Guangwen LUO ; Zhenyu QI ; Ke YUAN ; Shi WANG
Chinese Journal of Radiation Oncology 2014;23(2):156-160
Objective To evaluate the accuracy of image registration based on bony structure (RBS) and grey-scale (RGS) in positioning correction of radiation treatment,and their reliability in clinical application.Methods Setup errors of anthropomorphic phantom (chest& abdomen,head& neck) were simulated with x-,y-,z-directions.CBCT images were acquired for each simulation and registered with planning CT.using bony structure and grey-scale registration separately.Geometry accuracy of all registration were then obtained and analyzed.Results The errors of RBS and RGS in x-,y-,z-directions were (-0.65 ±0.22) mm and (-0.70±0.17) mm (P=0.00),(1.02 ±0.27) mm and (0.90±0.20) mm (P =0.00),(1.46 ± 0.53) mm and (1.47 ± 0.47) mm (P =0.54) for head& neck positioning; with (0.82±0.33) mm and (0.79±0.18) mm (P=0.03),(2.45±1.17) mm and (1.61 ±0.84) mm (P =0.00),(1.44 ± 3.25) mm and (0.19 ± 1.11) mm (P =0.00) for chest& abdomen positioning.Conclusions RGS is more accurate and stable than RBS.The accuracy of image registration is a little better for head& neck than that for chest& abdomen.The algorithms of image registration used in clinical application needs to be tested independently and the systematic error needs to be corrected before applying in different treatment techniques according to their accuracy requirement.

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