In the process of biological genetic information transmission,complete and correct genetic information can make cell mitosis proceed normally.In the development of most tumor cells,G2/M cell cycle checkpoint becomes t...In the process of biological genetic information transmission,complete and correct genetic information can make cell mitosis proceed normally.In the development of most tumor cells,G2/M cell cycle checkpoint becomes the key checkpoint in the process of mitosis due to the lack of G1/S cell cycle checkpoint,which mainly depends on the abnormal DNA information blocked by Wee1 protein kinase in G2 phase to enter M phase and prolong the time of G2 phase to complete DNA sequencing So that the normal genetic information can be passed on.Wee1 protein kinase expression is significantly increased in most tumor cells,making it a potential target for tumor therapy.展开更多
To explore the clinicopathological features of abound mitosis of the hepatocytes in intrahepatic cholelithiasis.The clinicopathological data of one case diagnosed as intrahepatic cholelithiasis was collected from Yant...To explore the clinicopathological features of abound mitosis of the hepatocytes in intrahepatic cholelithiasis.The clinicopathological data of one case diagnosed as intrahepatic cholelithiasis was collected from Yantai Yuhuangding Hospital and the clinicopathological characters were discussed.A 68-year-old man suffered from the pain in the right upper quadrant and radiology showed multiple stones in the gallbladder and left liver.The images suggested intrahepatic cholelithiasis.The patient received gallbladder and partial hepatectomy.A large number of mitosis was observed and twelve nuclear fissions were found under high magnification,even in some area pathological nuclear fission could be observed in morphology.On the basis of detection in laboratory,the diagnosis of intrahepatic cholelithiasis was made.The patient did not receive any therapy after surgery.The patient was in a good condition after 18 months follow-up.Increased number of hepatic mitosis might be due to the stimulation from stones,hepatic biliary or secondary inflammatory.High index of proliferation should be prevented from the potential misdiagnosis of hepatic tumor.展开更多
Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 i...Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.展开更多
Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we cond...Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.展开更多
To the Editor:With an aging global population,the incidences of community-acquired pneumonia(CAP)and chronic obstructive pulmonary disease(COPD)have signi cantly increased.[1]Previous studies have con rmed that COPD a...To the Editor:With an aging global population,the incidences of community-acquired pneumonia(CAP)and chronic obstructive pulmonary disease(COPD)have signi cantly increased.[1]Previous studies have con rmed that COPD and asthma are independently associated with the prevalence of CAP.The use of inhaled corticosteroid(ICS),the cornerstone of treatment for asthma,COPD with frequent acute exacerbations,and asthma-COPD overlap(ACO)may induce changes in the local lung microbiome and abnormal lung immunity,ultimately,causing a signi cantly increased risk of pneumonia.However,in cases of pneumonia,the effect of the use of ICS on CAP mortality remains controversial.While data from one study favored the prior use of ICS,which was associated with a signi cantly lower short-term mortality rate,[2]other studies have identi ed no impact on mortality.To date,data on the impact of the use of ICS on mortality,prehospitalization or during hospitalization,are scarce,particularly in the older population.Therefore,this multicenter,retrospective study explored the association between the use of ICS during hospitalization and short-term mortality in older patients with CAP and those with chronic pulmonary disease(CPD).展开更多
文摘In the process of biological genetic information transmission,complete and correct genetic information can make cell mitosis proceed normally.In the development of most tumor cells,G2/M cell cycle checkpoint becomes the key checkpoint in the process of mitosis due to the lack of G1/S cell cycle checkpoint,which mainly depends on the abnormal DNA information blocked by Wee1 protein kinase in G2 phase to enter M phase and prolong the time of G2 phase to complete DNA sequencing So that the normal genetic information can be passed on.Wee1 protein kinase expression is significantly increased in most tumor cells,making it a potential target for tumor therapy.
文摘To explore the clinicopathological features of abound mitosis of the hepatocytes in intrahepatic cholelithiasis.The clinicopathological data of one case diagnosed as intrahepatic cholelithiasis was collected from Yantai Yuhuangding Hospital and the clinicopathological characters were discussed.A 68-year-old man suffered from the pain in the right upper quadrant and radiology showed multiple stones in the gallbladder and left liver.The images suggested intrahepatic cholelithiasis.The patient received gallbladder and partial hepatectomy.A large number of mitosis was observed and twelve nuclear fissions were found under high magnification,even in some area pathological nuclear fission could be observed in morphology.On the basis of detection in laboratory,the diagnosis of intrahepatic cholelithiasis was made.The patient did not receive any therapy after surgery.The patient was in a good condition after 18 months follow-up.Increased number of hepatic mitosis might be due to the stimulation from stones,hepatic biliary or secondary inflammatory.High index of proliferation should be prevented from the potential misdiagnosis of hepatic tumor.
基金This study was funded by RemeGen Co.,Ltd.This work was also supported by the National Natural Science Foundation of China(No.91959205)the Ministry of Science and Technology of China(No.2017YFC1308900,No.2018ZX09201-015)Beijing Municipal Health Commission(No.2020-1-1022)。
文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.
基金Nanjing Luye Pharmaceutical Co.Ltd,Nanjing,China,Grant/Award Number:2017ZZ02012sponsored by Nanjing Luye Pharmaceu-tical Co.Ltd,Nanjing,China,and supported in part by grants from Shanghai Key disciplines of Respiratory(No.2017ZZ02012)and Shanghai Major Diseases Multidisci-plinary Cooperation Diagnosis and Treatment Construc-tion Project.
文摘Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.
基金supported by grants from the National Science Grant for Distinguished Young Scholars(No.81425001/H0104)the National Key Technology Support Program from the Ministry of Science and Technology(No.2015BAI12B11)the Beijing Science and Technology Project(No.D151100002115004)
文摘To the Editor:With an aging global population,the incidences of community-acquired pneumonia(CAP)and chronic obstructive pulmonary disease(COPD)have signi cantly increased.[1]Previous studies have con rmed that COPD and asthma are independently associated with the prevalence of CAP.The use of inhaled corticosteroid(ICS),the cornerstone of treatment for asthma,COPD with frequent acute exacerbations,and asthma-COPD overlap(ACO)may induce changes in the local lung microbiome and abnormal lung immunity,ultimately,causing a signi cantly increased risk of pneumonia.However,in cases of pneumonia,the effect of the use of ICS on CAP mortality remains controversial.While data from one study favored the prior use of ICS,which was associated with a signi cantly lower short-term mortality rate,[2]other studies have identi ed no impact on mortality.To date,data on the impact of the use of ICS on mortality,prehospitalization or during hospitalization,are scarce,particularly in the older population.Therefore,this multicenter,retrospective study explored the association between the use of ICS during hospitalization and short-term mortality in older patients with CAP and those with chronic pulmonary disease(CPD).
