AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2(COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery.METHODS: Patients undergoing open colorectal resection within an...AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2(COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery.METHODS: Patients undergoing open colorectal resection within an enhanced recovery after surgery protocol from 2011 to 2015 were reviewed. Patients with combined general anesthesia and epidural anesthesia, and those with acute colonic obstruction or perforation were excluded. Patients receiving selective COX-2 inhibitor were compared with well-matched individuals without such a drug. Outcome measures included numeric pain score and morphine milligram equivalent(MME) consumption on postoperative day(POD) 1-3, gastrointestinal recovery(time to tolerate solid diet and time to defecate), complications and length of postoperative stay.RESULTS: There were 75 patients in each group. Pain score on POD 1-3 was not significantly different between two groups. However, MME consumption and MME consumption per kilogram body weight on POD 1-3 was significantly less in patients receiving a selective COX-2 inhibitor(P < 0.001). Median MME consumption per kilogram body weight on POD 1-3 was 0.09, 0.06 and nil, respectively in patients receiving a selective COX-2 inhibitor and 0.22, 0.25 and 0.07, respectively in the comparative group(P < 0.001), representing at least 59% opioidreduction. Patients prescribing a selective COX-2 inhibitor had a shorter median time to resumption of solid diet [1(IQR 1-2) d vs 2(IQR 2-3) d; P < 0.001] and time to first defecation [2(IQR 2-3) d vs 3(IQR 3-4) d; P < 0.001]. There was no significant difference in overall postoperative complications between two groups. However, median postoperative stay was significantly 1-d shorter in patients prescribing a selective COX-2 inhibitor [4(IQR 3-5) d vs 5(IQR 4-6) d; P < 0.001]. CONCLUSION: Perioperative administration of oral selective COX-2 inhibitors significantly decreased intravenous opioid consumption, shortened time to gastrointestinal recovery and reduced hospital stay after open colorectal surgery.展开更多
The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have d...The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have designed and synthesized some promising compounds.展开更多
目的探讨前列地尔联合艾塞那肽对2型糖尿病患者的疗效及对血清脂肪特异性丝氨酸蛋白内抑制剂(vaspin)和内抑素(NES)的影响。方法选取130例糖尿病患者,随机均分为观察组和对照组,每组65例。对照组给予艾塞那肽治疗,观察组给予艾塞那肽联...目的探讨前列地尔联合艾塞那肽对2型糖尿病患者的疗效及对血清脂肪特异性丝氨酸蛋白内抑制剂(vaspin)和内抑素(NES)的影响。方法选取130例糖尿病患者,随机均分为观察组和对照组,每组65例。对照组给予艾塞那肽治疗,观察组给予艾塞那肽联合前列地尔治疗,治疗2周后观察2组患者的生化功能、血管功能、肾功能及血清Vaspin和NES水平。结果治疗前2组患者的生化功能、血管功能、肾功能及血清vaspin和NES水平比较差异无统计学意义,治疗后2组患者的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1C)、体质量指数(BMI)、空腹C肽、餐后2 h C肽、三酰甘油(TG)和总胆固醇(TC)均显著下降,观察组下降更显著(P<0.05);治疗后2组患者的尿总蛋白、尿素氮(BUN)和血肌酐(SCr)均显著下降,观察组下降更显著(P<0.05);治疗后2组患者的收缩期血管峰值血流速度(PSV)和内膜中层厚度(IMT)均降低,且观察组下降更显著,狭窄率均升高,且观察组升高更显著(P<0.05);治疗后2组患者的血清vaspin和NES水平均显著升高,且观察组升高更显著(P<0.05);2组患者均未出现严重的不良反应。结论前列地尔联合艾塞那肽治疗2型糖尿病患者的效果较好,可有效控制血糖,显著升高血清vaspin、NES水平,改善患者的血管功能、肾功能,降低糖尿病的并发症发生率。展开更多
HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific prot...HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.展开更多
文摘AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2(COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery.METHODS: Patients undergoing open colorectal resection within an enhanced recovery after surgery protocol from 2011 to 2015 were reviewed. Patients with combined general anesthesia and epidural anesthesia, and those with acute colonic obstruction or perforation were excluded. Patients receiving selective COX-2 inhibitor were compared with well-matched individuals without such a drug. Outcome measures included numeric pain score and morphine milligram equivalent(MME) consumption on postoperative day(POD) 1-3, gastrointestinal recovery(time to tolerate solid diet and time to defecate), complications and length of postoperative stay.RESULTS: There were 75 patients in each group. Pain score on POD 1-3 was not significantly different between two groups. However, MME consumption and MME consumption per kilogram body weight on POD 1-3 was significantly less in patients receiving a selective COX-2 inhibitor(P < 0.001). Median MME consumption per kilogram body weight on POD 1-3 was 0.09, 0.06 and nil, respectively in patients receiving a selective COX-2 inhibitor and 0.22, 0.25 and 0.07, respectively in the comparative group(P < 0.001), representing at least 59% opioidreduction. Patients prescribing a selective COX-2 inhibitor had a shorter median time to resumption of solid diet [1(IQR 1-2) d vs 2(IQR 2-3) d; P < 0.001] and time to first defecation [2(IQR 2-3) d vs 3(IQR 3-4) d; P < 0.001]. There was no significant difference in overall postoperative complications between two groups. However, median postoperative stay was significantly 1-d shorter in patients prescribing a selective COX-2 inhibitor [4(IQR 3-5) d vs 5(IQR 4-6) d; P < 0.001]. CONCLUSION: Perioperative administration of oral selective COX-2 inhibitors significantly decreased intravenous opioid consumption, shortened time to gastrointestinal recovery and reduced hospital stay after open colorectal surgery.
文摘The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have designed and synthesized some promising compounds.
文摘目的探讨前列地尔联合艾塞那肽对2型糖尿病患者的疗效及对血清脂肪特异性丝氨酸蛋白内抑制剂(vaspin)和内抑素(NES)的影响。方法选取130例糖尿病患者,随机均分为观察组和对照组,每组65例。对照组给予艾塞那肽治疗,观察组给予艾塞那肽联合前列地尔治疗,治疗2周后观察2组患者的生化功能、血管功能、肾功能及血清Vaspin和NES水平。结果治疗前2组患者的生化功能、血管功能、肾功能及血清vaspin和NES水平比较差异无统计学意义,治疗后2组患者的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1C)、体质量指数(BMI)、空腹C肽、餐后2 h C肽、三酰甘油(TG)和总胆固醇(TC)均显著下降,观察组下降更显著(P<0.05);治疗后2组患者的尿总蛋白、尿素氮(BUN)和血肌酐(SCr)均显著下降,观察组下降更显著(P<0.05);治疗后2组患者的收缩期血管峰值血流速度(PSV)和内膜中层厚度(IMT)均降低,且观察组下降更显著,狭窄率均升高,且观察组升高更显著(P<0.05);治疗后2组患者的血清vaspin和NES水平均显著升高,且观察组升高更显著(P<0.05);2组患者均未出现严重的不良反应。结论前列地尔联合艾塞那肽治疗2型糖尿病患者的效果较好,可有效控制血糖,显著升高血清vaspin、NES水平,改善患者的血管功能、肾功能,降低糖尿病的并发症发生率。
基金We extend our sincere appreciation to Mingyang Gao,Shuai Zhou,and Wenxiang Fang for their exceptional technical assistance.This research was financially supported by the National Natural Science Foundation of China(No.82103543)the Fundamental Research Funds for the Central Universities(No.WK9110000159,China)+1 种基金Natural Science Foundation of Anhui Province(No.2108085QH340,China)the Postdoctoral Science Foundation of China(No.2021M693082).
文摘HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.
