Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in case...Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant CRCs.Methods:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is imperative.Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed death ligand 1(PD-L1)expression.Results:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation sites.In comparison to the ERBB2 altered(alt)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt vs.ERBB2alt,KRAS:50.9%vs.25.6%,p<0.05;BRAF:8.5%vs.2.3%,p<0.05).32.7%(18/55)of CRCs with ERBB2 mutation exhibited microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed MSI-H.Mutant genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China.These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.展开更多
BACKGROUND Ciprofol is a novel agent for intravenous general anesthesia.In February 2022,it was approved by the National Medical Products Administration for general anesthesia induction and maintenance.It has the adva...BACKGROUND Ciprofol is a novel agent for intravenous general anesthesia.In February 2022,it was approved by the National Medical Products Administration for general anesthesia induction and maintenance.It has the advantages of fast onset,fast elimination,stable circulation,and few adverse reactions.However,the efficacy and safety of ciprofol in cardiac surgery with cardiopulmonary bypass have not been reported.Here we describe a case where ciprofol was successfully used for anesthesia in cardiac surgery with cardiopulmonary bypass.CASE SUMMARY A 72-year-old man(height 176 cm;weight 70 kg)was diagnosed with coronary atherosclerotic cardiomyopathy requiring coronary artery bypass grafting and left ventricular aneurysmectomy.Ciprofol was administered for induction(0.4 mg/kg)and maintenance(0.6-1.0 mg/kg/h)of general anesthesia.During the entire operation,the bispectral index,hemodynamics,and blood oxygen saturation were maintained at normal levels.The patient recovered well after surgery,with no serious adverse events related to ciprofol.CONCLUSION Ciprofol is safe and effective for anesthesia in cardiac surgery with cardiopulmonary bypass.展开更多
基金sponsored by National Natural Science Foundation of China(Grant Numbers 81972280,81972290)Natural Science Foundation of Shanghai(Grant Number 23ZR1452300)+2 种基金Research Grant for Health Science and Technology of Pudong Health Bureau of Shanghai(Grant Number PW2022E-02)Academic Leaders Training Program of Pudong Health Bureau of Shanghai(Grant Number PWRd2022-02)Foundation of Beijing CSCO Clinical Oncology Research(Grant Number Y-HR2019-0384).
文摘Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant CRCs.Methods:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is imperative.Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed death ligand 1(PD-L1)expression.Results:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation sites.In comparison to the ERBB2 altered(alt)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt vs.ERBB2alt,KRAS:50.9%vs.25.6%,p<0.05;BRAF:8.5%vs.2.3%,p<0.05).32.7%(18/55)of CRCs with ERBB2 mutation exhibited microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed MSI-H.Mutant genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China.These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.
文摘BACKGROUND Ciprofol is a novel agent for intravenous general anesthesia.In February 2022,it was approved by the National Medical Products Administration for general anesthesia induction and maintenance.It has the advantages of fast onset,fast elimination,stable circulation,and few adverse reactions.However,the efficacy and safety of ciprofol in cardiac surgery with cardiopulmonary bypass have not been reported.Here we describe a case where ciprofol was successfully used for anesthesia in cardiac surgery with cardiopulmonary bypass.CASE SUMMARY A 72-year-old man(height 176 cm;weight 70 kg)was diagnosed with coronary atherosclerotic cardiomyopathy requiring coronary artery bypass grafting and left ventricular aneurysmectomy.Ciprofol was administered for induction(0.4 mg/kg)and maintenance(0.6-1.0 mg/kg/h)of general anesthesia.During the entire operation,the bispectral index,hemodynamics,and blood oxygen saturation were maintained at normal levels.The patient recovered well after surgery,with no serious adverse events related to ciprofol.CONCLUSION Ciprofol is safe and effective for anesthesia in cardiac surgery with cardiopulmonary bypass.