Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia.Clostridium difficile infection(CDI)is a common nosocomial diarrheal disease.Disruption of normal intestinal flora by antib...Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia.Clostridium difficile infection(CDI)is a common nosocomial diarrheal disease.Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI.The use of broadspectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome.Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI.Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.展开更多
BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,i...BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.展开更多
Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although c...Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.展开更多
In regenerative medicine,effective management of tissue ischemia in surgical skin flaps is crucial,yet chal-lenging,particularly because inadequate blood flow often leads to necrosis at the distal flap tips.This study...In regenerative medicine,effective management of tissue ischemia in surgical skin flaps is crucial,yet chal-lenging,particularly because inadequate blood flow often leads to necrosis at the distal flap tips.This study aimed to examine the therapeutic potential of catalase-coated oxygen-generating microparticles embedded in gelatin methacryloyl(cOMP-GelMA)hydrogel to establish an optimized environment conducive to tissue regeneration.Using a large 3×9 cm^(2) rat random-pattern skin flap model,flap survival and regeneration were evaluated across four groups:control,pure GelMA hydrogel,and cOMP-GelMA hydrogel with two concentrations of cOMPs(0.2%and 0.5%w/v).These findings revealed that cOMP-GelMA comprising 0.2%OMP significantly enhanced angiogenesis,arteriogenesis,mitochondrial biogenesis,and antioxidant capacity compared to 0.5%cOMP-GelMA.Furthermore,the alleviation of the inflammatory response was more pronounced at lower cOMP concentrations than at higher concentrations.These results demonstrate that mild hypoxia,facilitated by moderate oxygen delivery,is beneficial for tissue repair and regeneration through peroxisome proliferatoractivated receptor gamma coactivator 1-alpha-and hypoxia-inducible factor 1-alpha-dependent signaling pathways.This study highlights the innovative aspect of using a large-scale model to explore the therapeutic benefits of mild hypoxia and suggests that controlled oxygen delivery by cOMPs can improve the long-term functional recovery of ischemic tissues.展开更多
A facile compositional tuning by Sb and Cu addition is performed to generate engineered defects in GeTe alloys with ultra-low thermal conductivity.Substitution of Sb and Cu at the Ge-site enhances the power factor due...A facile compositional tuning by Sb and Cu addition is performed to generate engineered defects in GeTe alloys with ultra-low thermal conductivity.Substitution of Sb and Cu at the Ge-site enhances the power factor due to the optimization of carrier concentration while maintaining the convergence of the valence bands.Furthermore,complex multi-dimensional defect structures including 0D(0-dimensional)substituted Sb_(Ge)and Cu_(Ge),2D twin and inversion boundaries,3D herringbone structures,3D embedded nanostructures,and 3D Cu-rich coherent precipitates are generated,which significantly reduce the lattice thermal conductivity benefitting from a collective phonon scattering.Due to this simultaneous manipulation of electronic and thermal transport properties,a maximum thermoelectric figure of merit(zT)of 1.4 was obtained at 723 K.展开更多
Objective:To investigate the changes in radial pulse induced by thermal stresses(TSs).Methods:Sixty subjects were enrolled.Using an open-label,2x2 crossover randomization design,both feet of each subject were immersed...Objective:To investigate the changes in radial pulse induced by thermal stresses(TSs).Methods:Sixty subjects were enrolled.Using an open-label,2x2 crossover randomization design,both feet of each subject were immersed in 15%:water for cold stress(CS)and in 40 X:water for heat stress(HS)for 5 min each.Radial pulse,respiration and electrocardiogram(ECG)signals were recorded before,during and immediately after the TSs.Results:The an alysis of heart rate variability revealed that CS in creased the low-freque ncy(LF)and high-frequency(HF)components(P<0.05)and that HS reduced the LF and HF components(P<0.01).Both TSs reduced the normalized LF,increased the normalized HF,and reduced the LF/HF ratio.The differences in the ECG signals were more dominant during the TS sessions,but those in the radial pulse signals became more domi nant immediately after the TS sessi ons.CS decreased the pulse depth(P<0.01)and in creased the radial augme ntation in dex(P<0.1),and HS in creased the pulse pressure(P<0.1)and sube ndocardial viability ratio(P<0.01).There were no significant differences in pulse rate during the three time sequences of each TS.The respiration rate was increased(P<0.1),and the pulse rate per respiration(P/R ratio)was significantly decreased(P<0.05)with CS.The HF region(10-30 Hz)of the pulse spectral density was suppressed during both TSs.Conclusions:CS induced vasoconstriction and sympathetic reactions,and HS induced vasodilation and parasympathetic reacti ons.Based on defi nitions used in pulse diag no sis,we made the novel discoveries that the pulse became slower(decreased P/R ratio),more floating and tenser under CS and that the HF region of the spectral power decreased significantly under both TSs.展开更多
文摘Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia.Clostridium difficile infection(CDI)is a common nosocomial diarrheal disease.Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI.The use of broadspectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome.Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI.Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.
文摘BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.
基金supported by St.Vincent’s Hospital,the Research Institute of Medical Science(Grant Number:SVHR-2021-03).
文摘Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
基金supported by a multidisciplinary research grant-in-aid from the Seoul Metropolitan Government Seoul National University(SMG-SNU)Boramae Medical Center(04-2023-0044)&SNU,Bio-MAX Institutea focused clinical research grant-in-aid from the Seoul Metropolitan GovernmentSeoul National University(SMG-SNU)Boramae Medical Center(04-2024-0017)+4 种基金a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(RS-2023-00213423 and RS-2024-00341578)a Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korean government(Ministry of Science and ICT,Ministry of Health&Welfare23A0202L1)funded by the National Institutes of Health(R01AR074234 and R01AR077132)AHA Collaborative Award(944227).
文摘In regenerative medicine,effective management of tissue ischemia in surgical skin flaps is crucial,yet chal-lenging,particularly because inadequate blood flow often leads to necrosis at the distal flap tips.This study aimed to examine the therapeutic potential of catalase-coated oxygen-generating microparticles embedded in gelatin methacryloyl(cOMP-GelMA)hydrogel to establish an optimized environment conducive to tissue regeneration.Using a large 3×9 cm^(2) rat random-pattern skin flap model,flap survival and regeneration were evaluated across four groups:control,pure GelMA hydrogel,and cOMP-GelMA hydrogel with two concentrations of cOMPs(0.2%and 0.5%w/v).These findings revealed that cOMP-GelMA comprising 0.2%OMP significantly enhanced angiogenesis,arteriogenesis,mitochondrial biogenesis,and antioxidant capacity compared to 0.5%cOMP-GelMA.Furthermore,the alleviation of the inflammatory response was more pronounced at lower cOMP concentrations than at higher concentrations.These results demonstrate that mild hypoxia,facilitated by moderate oxygen delivery,is beneficial for tissue repair and regeneration through peroxisome proliferatoractivated receptor gamma coactivator 1-alpha-and hypoxia-inducible factor 1-alpha-dependent signaling pathways.This study highlights the innovative aspect of using a large-scale model to explore the therapeutic benefits of mild hypoxia and suggests that controlled oxygen delivery by cOMPs can improve the long-term functional recovery of ischemic tissues.
基金supported by grants from the National Research Foundation(NRF)of Korea(No.2021R1A4A2001658)funded by the Korean government(MSIT).
文摘A facile compositional tuning by Sb and Cu addition is performed to generate engineered defects in GeTe alloys with ultra-low thermal conductivity.Substitution of Sb and Cu at the Ge-site enhances the power factor due to the optimization of carrier concentration while maintaining the convergence of the valence bands.Furthermore,complex multi-dimensional defect structures including 0D(0-dimensional)substituted Sb_(Ge)and Cu_(Ge),2D twin and inversion boundaries,3D herringbone structures,3D embedded nanostructures,and 3D Cu-rich coherent precipitates are generated,which significantly reduce the lattice thermal conductivity benefitting from a collective phonon scattering.Due to this simultaneous manipulation of electronic and thermal transport properties,a maximum thermoelectric figure of merit(zT)of 1.4 was obtained at 723 K.
基金Supported by the Korea Institute of Oriental Medicine funded by the Korean government(No.K17021)。
文摘Objective:To investigate the changes in radial pulse induced by thermal stresses(TSs).Methods:Sixty subjects were enrolled.Using an open-label,2x2 crossover randomization design,both feet of each subject were immersed in 15%:water for cold stress(CS)and in 40 X:water for heat stress(HS)for 5 min each.Radial pulse,respiration and electrocardiogram(ECG)signals were recorded before,during and immediately after the TSs.Results:The an alysis of heart rate variability revealed that CS in creased the low-freque ncy(LF)and high-frequency(HF)components(P<0.05)and that HS reduced the LF and HF components(P<0.01).Both TSs reduced the normalized LF,increased the normalized HF,and reduced the LF/HF ratio.The differences in the ECG signals were more dominant during the TS sessions,but those in the radial pulse signals became more domi nant immediately after the TS sessi ons.CS decreased the pulse depth(P<0.01)and in creased the radial augme ntation in dex(P<0.1),and HS in creased the pulse pressure(P<0.1)and sube ndocardial viability ratio(P<0.01).There were no significant differences in pulse rate during the three time sequences of each TS.The respiration rate was increased(P<0.1),and the pulse rate per respiration(P/R ratio)was significantly decreased(P<0.05)with CS.The HF region(10-30 Hz)of the pulse spectral density was suppressed during both TSs.Conclusions:CS induced vasoconstriction and sympathetic reactions,and HS induced vasodilation and parasympathetic reacti ons.Based on defi nitions used in pulse diag no sis,we made the novel discoveries that the pulse became slower(decreased P/R ratio),more floating and tenser under CS and that the HF region of the spectral power decreased significantly under both TSs.
