1.Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.
Yingying WANG ; Youping ZHANG ; Hao LUO ; Wei WEI ; Wanting LIU ; Weiwei WANG ; Yunzhao WU ; Cheng PENG ; Yanjie JI ; Jianfang ZHANG ; Chujiao ZHU ; Wenhui BAI ; Li XIA ; Hu LEI ; Hanzhang XU ; Leimiao YIN ; Wei WENG ; Li YANG ; Ligen LIU ; Aiwu ZHOU ; Yueyue WEI ; Qi ZHU ; Weiliang ZHU ; Yongqing YANG ; Zhijian XU ; Yingli WU
Acta Pharmaceutica Sinica B 2024;14(12):5235-5248
Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.
2.End-to-end bile duct anastomosis and percutaneous transhepatic cholangial drainage for iatrogenic bile duct injuries
Changku JIA ; Sunbing XU ; Hongwei CHEN ; Wei CHEN ; Xinyu CHEN ; Hanzhang ZHU ; Ling LIU
Chinese Journal of Hepatobiliary Surgery 2022;28(2):108-112
Objective:A novel bile duct end-to-end anastomosis and percutaneous transhepatic cholangial drainage (PTCD) were designed to treat iatrogenic bile duct injuries, and the clinical efficacy and technical advantage of this combined treatment were analyzed.Methods:Clinical data from 11 patients with iatrogenic bile duct injuries treated between February 2012 to July 2021 was retrospectively analyzed. There were 4 females and 7 males, with age of (47.5±15.3) years old. The types of bile duct injuries were: Bismuth type 1 ( n=7), Bismuth type Ⅱ ( n=1), Bismuth type Ⅲ type ( n=1), combined Bismuth type 1 and type 2 ( n=1), and Bismuth type Ⅳ ( n=1). Repair operations were performed at the time of the initial surgical procedures in 8 patients. The remaining 3 patients had their repair done 2 days, 9 days and 5 months, respectively, after the initial operations. All patients underwent successful bile duct end-to-end anastomosis and PTCD without use of T-tubes. Results:All biliary injuries were successfully repaired with no operative mortalities. Two patients who underwent end-to-end anastomosis of common hepatic duct developed anastomotic bile leakage. The amount of bile leakage was small and bile leakage resolved with conservative treatment in 1 patients 3 days after surgery, and was treated successfully by percutaneous peritoneal drainage for 2 weeks in the other patient. There were no other complications, including stricture formation or cholangitis which developed in other patients. All patients’ liver functions recovered well. The percutaneous biliary drainage tube was removed 6 months after operation in 1 patient. The remaining patients had their drainage tubes removed 3 months after operation. On follow-up, all patients had no history suggestive of cholangitis, jaundice and other symptoms. The liver functions were normal on laboratory examinations. No stricture or dilatation of intrahepatic bile ducts were detected on imaging examinations. The cure rate was 100% (11/11).Conclusion:Surgical repair of biliary tract injuries should aim to preserve sphincter of Oddi function and maintain normal physiological pathway of bile excretion. PTCD helped smooth recovery of an end-to-end anastomosis, lowered severity of physical disability of patients and minimized occurrence of medical disputes.
3.Clinical application of lung transplantation with size reduced graft lung
Xin XU ; Hanzhang CHEN ; Weiqiang YIN ; Dong XIAO ; Bing WEI ; Jun LIU ; Yuan QIU ; Linhu GE ; Jianxing HE
Chinese Journal of Postgraduates of Medicine 2009;32(29):11-13
Objective To report the experience of lung transplantation with size reduced graft lung.Methods Four cases receiving lung transplantation with size reduced graft lung were analyzed retrospectively.In case 1,left lung transplantation combined with contra-hteral lung volume mduction.In case 2,right lung transplantation Wag individually performed with partially msecfion of upper lobe of graft lung.In case 3.bilateral sequential lung transplantation wag performed using graft lung with partially resection of bilateral upper lobes.In the remained ease,bilateral sequential lung tansplantation was performed using graft lung with resection of right lower lobe.Results All the size reduced graft lungs had good functions during the peri-operation period.Case 1 and case 2 still survived without obvious complication.Case 3 experienced temporary air leak on the 5th day postoperation and cured by water seal drainage but died of abrupt bronchorrhea due to aspergillus infection on the 32th day postoperation.The last cage experienced smoothly recovery excepted fatal virus pneumonia 2 months postopemtion.Conclusion Size reduced graft lungs can be successfully used for transplantation.
4.Allogenic single-lung transplantation for chronic obstructive pulmonary disease in 4 cases
Dong CUI ; Linhu GE ; Jianxing HE ; Xin XU ; Hanzhang CHEN ; Weiqiang YIN
Chinese Journal of Tissue Engineering Research 2008;12(53):10571-10574
Clinical data of 4 patients with chronic obstructive pulmonary disease who underwent allogenic single-lung transplantation were retrospectively analyzed. All cases received corpse donor lungs. One case with diffuse emphysema underwent right lung transplantation. and 3 received left lung transplantation. including one underwent fight lung volume reduction during surgery and 2 cases underwent right lung volume reduction post-transplantation. The inductive treatment with daclizumab or antithymocyte globulin was done and the rejection was prevented with Tacrolimus. mycophenolate and prednisone. The surgery was successfulin 4 cases. One case developed acute rejection on the fifth day post-transplantation. and controlled using methylprednisolone. Two cases discharged successfully, of whom one lived more than 2 years. Two cases died 74 days and 77 days after lung transplantation. respectively.
5.Massive concha bullosa pyocele with orbital extension--a case report and review of the literature.
Yu XU ; Zezhang TAO ; Hanzhang ZHAN ; Tao ZHOU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2007;21(23):1085-1086
OBJECTIVE:
To discuss the complication of common anatomic variant of the middle turbinate-concha bullosa.
METHOD:
We present a 35 years old man with inner canthus proptosis and orbital pain who was diagnosed to be a pyocele originated from concha bullosa by CT and operation.
RESULT:
Concha bullosa can develop to a pyocele. Direct extension of the mass from the nose into the orbit may occur. Good therapeutic effect was obtained by endoscopic operation.
CONCLUSION
Concha bullosa can result in obstruction of middle meatus and lead to sinusitis. Polyps or mucocele may also occur to Concha bullosa itself. Pyocele of concha bullosa can develop to such a massive extent that it leads to orbital complication. Endoscopic operation is best treatment to this disease.
Adult
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Endoscopy
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Humans
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Male
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Mucocele
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pathology
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surgery
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Nose Diseases
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pathology
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surgery
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Orbit
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pathology
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Turbinates

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