Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an acti...Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.展开更多
Background Transurethral resection of the bladder tumor （TURBT） remains the gold standard for non-muscle-invasive bladder cancer （NMIBC）. Laser techniques have been widely used in urology. This analysis aimed to a...Background Transurethral resection of the bladder tumor （TURBT） remains the gold standard for non-muscle-invasive bladder cancer （NMIBC）. Laser techniques have been widely used in urology. This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor （HoLRBT）vs. TURBT. Methods A systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated. Results Five studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups （weighted mean difference （WMD） 1.01, 95% confidential interval （95% CI） -3.52-5.54, P=0.66）. The significant difference in the obturator nerve reflex （OR 0.05, 95% CI 0.01-0.04, P=0.004）, bladder perforation （OR 0.14, 95% CI 0.03-0.61, P=-0.009）, bladder irrigation （OR 0.13, 95% CI 0.04-0.45, P=0.001）, catheterization time （WMD -0.96, 95% C1-1.11 to-0.82, P 〈0.00001）, and hospital stay （WMD-1.46, 95% C1-1.65 to-1.27, P 〈0.00001）showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group （OR 1.46, 95% CI 1.02-2.11, P=-0.04）. Conclusions As a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.展开更多
Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases...Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.展开更多
Intra-abdominal hypertension(IAH)and abdominal compartment syndrome are well recognized entities among surgical patients.Nevertheless,a number of prospective and retrospective observational studies have shown that IAH...Intra-abdominal hypertension(IAH)and abdominal compartment syndrome are well recognized entities among surgical patients.Nevertheless,a number of prospective and retrospective observational studies have shown that IAH is prevalent in about half of the critically ill patients in the medical intensive care units(ICU)and has been widely recognized as an independent risk factor for mortality.It is alarming to note that many members of the critical care team in medical ICU are not aware of the consequences of untreated IAH and the delay in making the diagnosis leads to increased morbidity and mortality.Frequently it is underdiagnosed and undertreated in this patient population.Elevated intraabdominal pressure decreases the blood flow to the kidneys and other abdominal viscera and also results in reduced cardiac output and difficulties in ventilating the patient because of increased intrathoracic pressure.When intraabdominal hypertension is not promptly recognized and treated,it leads to abdominal compartment syndrome,multiorgan dysfunction syndrome and death.Large volume fluid resuscitation is very common in medical ICU patients presenting with sepsis,shock and other inflammatory conditions like pancreatitis and it is one of the major risk factors for the development of intra-abdominal hypertension.This article presents an overview of the epidemiology,definitions,risk factors,pathophysiology and management of IAH and abdominal compartment syndrome in critically ill medical ICU patients.展开更多
Background:As a rate-limiting enzyme of glycolysis,pyruvate kinase muscle isozyme M2(PKM2)participates in tumor metabolism and growth.The regulatory network of PKM2 in cancer is complex and has not been fully studied ...Background:As a rate-limiting enzyme of glycolysis,pyruvate kinase muscle isozyme M2(PKM2)participates in tumor metabolism and growth.The regulatory network of PKM2 in cancer is complex and has not been fully studied in bladder cancer.The 5-methylcytidine(m5C)modification in PKM2 mRNA might participate in the pathogenesis of bladder cancer and need to be further clarified.This study aimed to investigate the biological function and regulatory mechanism of PKM2 in bladder cancer.Methods:The expression of PKM2 and Aly/REF export factor(ALYREF)was measured by Western blotting,qRT-PCR,and immunohistochemistry.The bioprocesses of bladder cancer cells were demonstrated by a series of experiments in vitro and in vivo.RNA immunoprecipitation,RNA-sequencing,and dualluciferase reporter assays were conducted to explore the potential regulatory mechanisms of PKM2 in bladder cancer.Results:In bladder cancer,we first demonstrated that ALYREF stabilized PKM2 mRNA and bound to its m5C sites in 3′-untranslated regions.Overexpression of ALYREF promoted bladder cancer cell proliferation by PKM2-mediated glycolysis.Furthermore,high expression of PKM2 and ALYREF predicted poor survival in bladder cancer patients.Finally,we found that hypoxia-inducible factor-1alpha(HIF-1α)indirectly up-regulated the expression of PKM2 by activating ALYREF in addition to activating its transcription directly.Conclusions:The m5C modification in PKM2 mRNA in the HIF-1α/ALYREF/PKM2 axis may promote the glucose metabolism of bladder cancer,providing a new promising therapeutic target for bladder cancer.展开更多
AIM： To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent （EMS） used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS...AIM： To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent （EMS） used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS： Fourteen patients diagnosed with obstructive jaundice due to unresectable malignancies were included in the study. The malignancies in these patients were a result of very advanced carcinoma or old age. Percutaneous transhepatic cholangiography was performed under ultrasonographic guidance. After a catheter with an inner metallic guide was advanced into the duodenum, an EMS was placed in the common bile duct, between a point 1 cm beyond the papilla of Vater and the entrance to the hepatic hilum. In cases where it was difficult to span the distance using just a single EMS, an additional stent was positioned. A drainage catheter was left in place to act as a hemostat. The catheter was removed after resolution of cholestasis and stent patency was confirmed 2 or 3 d post-procedure. RESULTS： One-step insertion of the EMS was achieved in all patients with a procedure mean time of 24.4 min. Out of the patients who required 2 EMS, 4 needed a procedure time exceeding 30 min. The mean time for removal of the catheter post-procedure was 2.3 d. All patients died of malignancy with a mean follow-up time of 7.8 mo. No stent-related complication or stent obstruction was encountered. CONCLUSIONS： One-step percutaneous transhepaticinsertion of EMS is a simple procedure for resolving biliary obstruction and can effectively improve the patient＇s quality of life.展开更多
基金supported by the grants National Natural Science Foundation of China (Nos. 81874380 and 82022075, to Xinbing Sui81730108 and 81973635, to Tian Xie)+4 种基金Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars (No. LR18H160001, to Xinbing Sui)Zhejiang Provincial Natural Science Foundation of China (Nos. LQ20H160013, Ting DuanLQ21H160038, to Jiao Feng)Zhejiang Province Science and Technology Project of TCM (Nos. 2019ZZ016, to Xinbing Sui2020ZQ046, to Ruonan Zhang, China)。
文摘Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.
文摘Background Transurethral resection of the bladder tumor （TURBT） remains the gold standard for non-muscle-invasive bladder cancer （NMIBC）. Laser techniques have been widely used in urology. This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor （HoLRBT）vs. TURBT. Methods A systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated. Results Five studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups （weighted mean difference （WMD） 1.01, 95% confidential interval （95% CI） -3.52-5.54, P=0.66）. The significant difference in the obturator nerve reflex （OR 0.05, 95% CI 0.01-0.04, P=0.004）, bladder perforation （OR 0.14, 95% CI 0.03-0.61, P=-0.009）, bladder irrigation （OR 0.13, 95% CI 0.04-0.45, P=0.001）, catheterization time （WMD -0.96, 95% C1-1.11 to-0.82, P 〈0.00001）, and hospital stay （WMD-1.46, 95% C1-1.65 to-1.27, P 〈0.00001）showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group （OR 1.46, 95% CI 1.02-2.11, P=-0.04）. Conclusions As a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.
文摘Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.
文摘Intra-abdominal hypertension(IAH)and abdominal compartment syndrome are well recognized entities among surgical patients.Nevertheless,a number of prospective and retrospective observational studies have shown that IAH is prevalent in about half of the critically ill patients in the medical intensive care units(ICU)and has been widely recognized as an independent risk factor for mortality.It is alarming to note that many members of the critical care team in medical ICU are not aware of the consequences of untreated IAH and the delay in making the diagnosis leads to increased morbidity and mortality.Frequently it is underdiagnosed and undertreated in this patient population.Elevated intraabdominal pressure decreases the blood flow to the kidneys and other abdominal viscera and also results in reduced cardiac output and difficulties in ventilating the patient because of increased intrathoracic pressure.When intraabdominal hypertension is not promptly recognized and treated,it leads to abdominal compartment syndrome,multiorgan dysfunction syndrome and death.Large volume fluid resuscitation is very common in medical ICU patients presenting with sepsis,shock and other inflammatory conditions like pancreatitis and it is one of the major risk factors for the development of intra-abdominal hypertension.This article presents an overview of the epidemiology,definitions,risk factors,pathophysiology and management of IAH and abdominal compartment syndrome in critically ill medical ICU patients.
基金supported by grants from the National Natural Science Foundation of China(81602235,81772711)the“333”project of Jiangsu Province(LGY2018055,LGY2016002)+2 种基金Key Provincial Talents Program of Jiangsu Province(ZDRCA2016006)the Priority Academic Program Development of Jiangsu Higher Education Institutions(JX10231801)the Provincial Initiative Program for Excellency Disciplines of Jiangsu Province(BE2016791).
文摘Background:As a rate-limiting enzyme of glycolysis,pyruvate kinase muscle isozyme M2(PKM2)participates in tumor metabolism and growth.The regulatory network of PKM2 in cancer is complex and has not been fully studied in bladder cancer.The 5-methylcytidine(m5C)modification in PKM2 mRNA might participate in the pathogenesis of bladder cancer and need to be further clarified.This study aimed to investigate the biological function and regulatory mechanism of PKM2 in bladder cancer.Methods:The expression of PKM2 and Aly/REF export factor(ALYREF)was measured by Western blotting,qRT-PCR,and immunohistochemistry.The bioprocesses of bladder cancer cells were demonstrated by a series of experiments in vitro and in vivo.RNA immunoprecipitation,RNA-sequencing,and dualluciferase reporter assays were conducted to explore the potential regulatory mechanisms of PKM2 in bladder cancer.Results:In bladder cancer,we first demonstrated that ALYREF stabilized PKM2 mRNA and bound to its m5C sites in 3′-untranslated regions.Overexpression of ALYREF promoted bladder cancer cell proliferation by PKM2-mediated glycolysis.Furthermore,high expression of PKM2 and ALYREF predicted poor survival in bladder cancer patients.Finally,we found that hypoxia-inducible factor-1alpha(HIF-1α)indirectly up-regulated the expression of PKM2 by activating ALYREF in addition to activating its transcription directly.Conclusions:The m5C modification in PKM2 mRNA in the HIF-1α/ALYREF/PKM2 axis may promote the glucose metabolism of bladder cancer,providing a new promising therapeutic target for bladder cancer.
文摘AIM： To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent （EMS） used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS： Fourteen patients diagnosed with obstructive jaundice due to unresectable malignancies were included in the study. The malignancies in these patients were a result of very advanced carcinoma or old age. Percutaneous transhepatic cholangiography was performed under ultrasonographic guidance. After a catheter with an inner metallic guide was advanced into the duodenum, an EMS was placed in the common bile duct, between a point 1 cm beyond the papilla of Vater and the entrance to the hepatic hilum. In cases where it was difficult to span the distance using just a single EMS, an additional stent was positioned. A drainage catheter was left in place to act as a hemostat. The catheter was removed after resolution of cholestasis and stent patency was confirmed 2 or 3 d post-procedure. RESULTS： One-step insertion of the EMS was achieved in all patients with a procedure mean time of 24.4 min. Out of the patients who required 2 EMS, 4 needed a procedure time exceeding 30 min. The mean time for removal of the catheter post-procedure was 2.3 d. All patients died of malignancy with a mean follow-up time of 7.8 mo. No stent-related complication or stent obstruction was encountered. CONCLUSIONS： One-step percutaneous transhepaticinsertion of EMS is a simple procedure for resolving biliary obstruction and can effectively improve the patient＇s quality of life.
