BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explo...BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.展开更多
Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregul...Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.展开更多
AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in a...AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.展开更多
We study the subhalo and satellite populations in haloes similar to the Milky Way(MW)-Andromeda paired configuration in the Millennium II and P-Millennium simulations.We find subhaloes are 5%–15%more abundant in pair...We study the subhalo and satellite populations in haloes similar to the Milky Way(MW)-Andromeda paired configuration in the Millennium II and P-Millennium simulations.We find subhaloes are 5%–15%more abundant in paired haloes than their isolated counterparts that have the same halo mass and large-scale environmental density.Paired haloes tend to reside in a more isotropic environment than isolated haloes,the shear tensor of their large-scale tidal field is possibly responsible for this difference.We also study the thickness of the spatial distribution of the top 11 most massive satellite galaxies obtained in the semi-analytic galaxy sample constructed from the Millennium II simulation.Moreover,satellites that have lost their host subhaloes due to the resolution limit of the simulation have been taken into account.As a result,we find that the difference in the distribution of the satellite thickness between isolated and paired haloes is indistinguishable,which suggests that the paired configuration is not responsible for the observed plane of satellites in the MW.The results in this study indicate the paired configuration could bring some nonnegligible effect on the subhalo abundance in the investigation of the MW's satellite problems.展开更多
Background The goal of this study was to explore the significance of left ventricular(LV)ejection/filling parameters in assessing severity and prognosis of pulmonary arterial hypertension(PAH).Methods Newly diagnosed ...Background The goal of this study was to explore the significance of left ventricular(LV)ejection/filling parameters in assessing severity and prognosis of pulmonary arterial hypertension(PAH).Methods Newly diagnosed PAH patients were recruited between July 2011 and December 2013 prospectively.Cardiopulmonary hemodynamics derived from right heart catheterization,and LV ejection/filling parameters derived from CMR were collected.Follow-up data were collected periodically using a specifically-designed network database until April 30,2016.展开更多
Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with pos...Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with post splenectomy pulmonary hypertension admitted to our hospital from October 2006 to March 2017 were systematically reviewed.展开更多
Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of ...Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of Warburg effect in the lung tissue of idiopathic pulmonary arterial hypertension patients.However the relationships and the underlying mechanisms between EndoMT and Warburg effect have not been elucidated.Therefore,the purpose of this study is to determine whether metabolic reprogramming happens in EndoMT cells.We also want to investigate whether sodium dichloroacetate(DCA),a metabolic modulator,could prevent EndoMT by inhibiting Warburg effect.展开更多
We study the relation between halo concentration and mass(c-M relation) using galaxy catalogs of the Seventh and Eighth Data Releases of the Sloan Digital Sky Survey(SDSS DR7 and DR8). Assuming that the satellite gala...We study the relation between halo concentration and mass(c-M relation) using galaxy catalogs of the Seventh and Eighth Data Releases of the Sloan Digital Sky Survey(SDSS DR7 and DR8). Assuming that the satellite galaxies follow the distribution of dark matter, we derive the halo concentration by fitting the satellite radial profile with a Nararro Frank and White(NFW) format. The derived c-M relation covers a wide halo mass range from10^(11.6)to 10^(14.1)M_(⊙). We confirm the anti-correlation between the halo mass and concentration as predicted in cosmological simulations. Our results are in good agreement with those derived using galaxy dynamics and gravitational lensing for halos of 10^(11.6)– 10^(12.9)M_(⊙), while they are slightly lower for halos of 10^(12.9)– 10^(14.1)M_(⊙).This is because blue satellite galaxies are less concentrated, especially in the inner regions. Instead of using all satellite galaxies, red satellites could be better tracers of the underlying dark matter distribution in galaxy groups.展开更多
BACKGROUND Colonoscopy has become a routine physical examination as people’s health awareness has increased.Polyethylene glycol(PEG)is greatly used in bowel preparation before colonoscopy due to its price and safety ...BACKGROUND Colonoscopy has become a routine physical examination as people’s health awareness has increased.Polyethylene glycol(PEG)is greatly used in bowel preparation before colonoscopy due to its price and safety advantages.Septic shock after colonoscopy with PEG preparation is extremely rare,with only very few cases in critically ill patients.Herein,we describe a case of septic shock in a healthy young adult immediately following colonoscopy with PEG preparation.CASE SUMMARY A 33-year-old young adult presented to our hospital for colonoscopy with PEG bowel preparation due to recurrent diarrhea for 7 years.The male's previous physical examination showed no abnormal indicators,and colonoscopy results were normal;however,he exhibited septic shock and markedly elevated white blood cell,C-reactive protein,and procalcitonin levels on the second day after colonoscopy.Immediate resuscitation and intensive care with appropriate antibiotics improved his condition.However,the blood and stool cultures did not detect the pathogen CONCLUSION Septic shock after colonoscopy is rare,especially in young adults.The authors considered the possibility of opportunistic infections after PEG bowel preparation,and clinicians should monitor patients for the possibility of such complications.展开更多
Airborne transmission is among the most frequent types of nosocomial infection.Recent years have witnessed frequent outbreaks of airborne diseases,such as severe acute respiratory syndrome(SARS)in 2002,Middle East res...Airborne transmission is among the most frequent types of nosocomial infection.Recent years have witnessed frequent outbreaks of airborne diseases,such as severe acute respiratory syndrome(SARS)in 2002,Middle East respiratory syndrome(MERS)in 2012,and coronavirus disease 2019(COVID-19),with the latter being on the rampage since the end of 2019 and bringing the effect of aerosols on health back to the fore(Gralton et al.,2011;Wang et al.,2021).An increasing number of studies have shown that certain highly transmissible pathogens can maintain long-term stability and efficiently spread through aerosols(Leung,2021;Lv et al.,2021).As reported previously,influenza viruses that can spread efficiently through aerosols remain stable for a longer period compared to those that cannot.The World Health Organization(WHO)has stated that aerosol-generating procedures(AGPs)play an important role in aerosol transmission in hospitals(Calderwood et al.,2021).AGPs,referring to medical procedures that produce aerosols,including dental procedures,endotracheal intubation,sputum aspiration,and laparoscopic surgeries,have been reported to be significantly associated with an increased risk of nosocomial infection among medical personnel(Hamilton,2021).展开更多
Metastatic pancreatic cancer(mPC)has a dismal prognosis.Herein,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-pa...Metastatic pancreatic cancer(mPC)has a dismal prognosis.Herein,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and safety.In 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,respectively.Grade 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer PFS.Additionally,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy.In conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC.The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.展开更多
Rhodium(III)-catalyzed enantioselective C-H indolylization of isoquinolines was developed.The C-H coupling reactions between 1-aryl isoquinoline derivatives and 3-indolylphenyliodonium salts proceeded smoothly in the ...Rhodium(III)-catalyzed enantioselective C-H indolylization of isoquinolines was developed.The C-H coupling reactions between 1-aryl isoquinoline derivatives and 3-indolylphenyliodonium salts proceeded smoothly in the presence of a modified chiral cyclopentadienyl-Rh(III)complex,affording a series of axially chiral indolylated biaryl products in excellent yields and enantioselectivity(up to 98%yield and 95%ee).展开更多
Chiral dihydrobenzofuran is a valuable synthetic fragment in both medicinal and organic chemistry.Efficient rhodium(Ⅲ)-catalyzed chemoselective and enantioselective C-H functionalization/[3+2]annulation of N-phenoxya...Chiral dihydrobenzofuran is a valuable synthetic fragment in both medicinal and organic chemistry.Efficient rhodium(Ⅲ)-catalyzed chemoselective and enantioselective C-H functionalization/[3+2]annulation of N-phenoxyacetamides with 1,3-dienes is reported.In the presence of 5 mol%Cp Rh complex,various chiral dihydrobenzofurans were synthesized in up to 79%yield and 98%ee.This reaction proceeds under mild conditions with excellent functional group compatibility.展开更多
基金Supported by The Key Research and Development Projects of Sichuan Science and Technology Department,No.2023YFS0285Natural Science Foundation Project of Sichuan Science and Technology Department,No.2023NSFSC0613.
文摘BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.
文摘Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.
基金Supported by National Natural Science Foundation of China(No.81100681)
文摘AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.
基金supported by the National Key R&D Program of China(Nos.2018YFE0202900 and 2022YFA1602901)by the NSFC Grant(Nos.11988101,11873051,12125302 and 12273053)+6 种基金support from the K.C.Wong Education Foundationthe support of CAS Project for Young Scientists in Basic Research,grant No.YSBR-062the science research grants from the China Manned Spaced Project with No.CMS-CSST-2021-B03the support of the National Natural Science Foundation of China(Nos.12047569 and 12147217)the Natural Science Foundation of Jilin Province,China(No.20180101228JC)funded by BIS National E-infrastructure capital grant ST/K00042X/1,STFC capital grant ST/H008519/1STFC Di RAC Operations grant ST/K003267/1 and Durham University。
文摘We study the subhalo and satellite populations in haloes similar to the Milky Way(MW)-Andromeda paired configuration in the Millennium II and P-Millennium simulations.We find subhaloes are 5%–15%more abundant in paired haloes than their isolated counterparts that have the same halo mass and large-scale environmental density.Paired haloes tend to reside in a more isotropic environment than isolated haloes,the shear tensor of their large-scale tidal field is possibly responsible for this difference.We also study the thickness of the spatial distribution of the top 11 most massive satellite galaxies obtained in the semi-analytic galaxy sample constructed from the Millennium II simulation.Moreover,satellites that have lost their host subhaloes due to the resolution limit of the simulation have been taken into account.As a result,we find that the difference in the distribution of the satellite thickness between isolated and paired haloes is indistinguishable,which suggests that the paired configuration is not responsible for the observed plane of satellites in the MW.The results in this study indicate the paired configuration could bring some nonnegligible effect on the subhalo abundance in the investigation of the MW's satellite problems.
文摘Background The goal of this study was to explore the significance of left ventricular(LV)ejection/filling parameters in assessing severity and prognosis of pulmonary arterial hypertension(PAH).Methods Newly diagnosed PAH patients were recruited between July 2011 and December 2013 prospectively.Cardiopulmonary hemodynamics derived from right heart catheterization,and LV ejection/filling parameters derived from CMR were collected.Follow-up data were collected periodically using a specifically-designed network database until April 30,2016.
文摘Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with post splenectomy pulmonary hypertension admitted to our hospital from October 2006 to March 2017 were systematically reviewed.
文摘Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of Warburg effect in the lung tissue of idiopathic pulmonary arterial hypertension patients.However the relationships and the underlying mechanisms between EndoMT and Warburg effect have not been elucidated.Therefore,the purpose of this study is to determine whether metabolic reprogramming happens in EndoMT cells.We also want to investigate whether sodium dichloroacetate(DCA),a metabolic modulator,could prevent EndoMT by inhibiting Warburg effect.
基金supported by the National Key Research and Development of China (No. 2018YFA0404503)NSFC (grant Nos. 12033008 and 11988101)+4 种基金the K.C.Wong Education Foundation, and the science research grants from the China Manned Space Project with Nos. CMS-CSST-2021-A03 and CMS-CSST-2021-A07support from the joint Sino-German DFG research Project The Cosmic Web and its impact on galaxy formation and alignment (DFG-LI 2015/5-1, NSFC No. 11861131006)the support of the Shanghai International partners project (No. 19590780200)the support from NSFC (12022307)the Yangyang Development Fund。
文摘We study the relation between halo concentration and mass(c-M relation) using galaxy catalogs of the Seventh and Eighth Data Releases of the Sloan Digital Sky Survey(SDSS DR7 and DR8). Assuming that the satellite galaxies follow the distribution of dark matter, we derive the halo concentration by fitting the satellite radial profile with a Nararro Frank and White(NFW) format. The derived c-M relation covers a wide halo mass range from10^(11.6)to 10^(14.1)M_(⊙). We confirm the anti-correlation between the halo mass and concentration as predicted in cosmological simulations. Our results are in good agreement with those derived using galaxy dynamics and gravitational lensing for halos of 10^(11.6)– 10^(12.9)M_(⊙), while they are slightly lower for halos of 10^(12.9)– 10^(14.1)M_(⊙).This is because blue satellite galaxies are less concentrated, especially in the inner regions. Instead of using all satellite galaxies, red satellites could be better tracers of the underlying dark matter distribution in galaxy groups.
文摘BACKGROUND Colonoscopy has become a routine physical examination as people’s health awareness has increased.Polyethylene glycol(PEG)is greatly used in bowel preparation before colonoscopy due to its price and safety advantages.Septic shock after colonoscopy with PEG preparation is extremely rare,with only very few cases in critically ill patients.Herein,we describe a case of septic shock in a healthy young adult immediately following colonoscopy with PEG preparation.CASE SUMMARY A 33-year-old young adult presented to our hospital for colonoscopy with PEG bowel preparation due to recurrent diarrhea for 7 years.The male's previous physical examination showed no abnormal indicators,and colonoscopy results were normal;however,he exhibited septic shock and markedly elevated white blood cell,C-reactive protein,and procalcitonin levels on the second day after colonoscopy.Immediate resuscitation and intensive care with appropriate antibiotics improved his condition.However,the blood and stool cultures did not detect the pathogen CONCLUSION Septic shock after colonoscopy is rare,especially in young adults.The authors considered the possibility of opportunistic infections after PEG bowel preparation,and clinicians should monitor patients for the possibility of such complications.
基金supported by the Medicine and Health Care in Zhejiang Province Science and Technology Plan Projects(Nos.2020KY552 and 2021PY006)the Commonweal Project of Science and Technology Department of Zhejiang Province(No.LGF21H030007),China.
文摘Airborne transmission is among the most frequent types of nosocomial infection.Recent years have witnessed frequent outbreaks of airborne diseases,such as severe acute respiratory syndrome(SARS)in 2002,Middle East respiratory syndrome(MERS)in 2012,and coronavirus disease 2019(COVID-19),with the latter being on the rampage since the end of 2019 and bringing the effect of aerosols on health back to the fore(Gralton et al.,2011;Wang et al.,2021).An increasing number of studies have shown that certain highly transmissible pathogens can maintain long-term stability and efficiently spread through aerosols(Leung,2021;Lv et al.,2021).As reported previously,influenza viruses that can spread efficiently through aerosols remain stable for a longer period compared to those that cannot.The World Health Organization(WHO)has stated that aerosol-generating procedures(AGPs)play an important role in aerosol transmission in hospitals(Calderwood et al.,2021).AGPs,referring to medical procedures that produce aerosols,including dental procedures,endotracheal intubation,sputum aspiration,and laparoscopic surgeries,have been reported to be significantly associated with an increased risk of nosocomial infection among medical personnel(Hamilton,2021).
基金National Key Research and Development Program of China(2020YFA0713804)the National Natural Science Foundation of China(82272811)+2 种基金Jiangsu Province Key Research and Development Program(BE2023654)Nanjing Jiangbei New Area Key Research and Development Program,Special Fund of Health Science and Technology Development of Nanjing(YKK20080)Fundings for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University(2023-LCYJ-PY-29).
文摘Metastatic pancreatic cancer(mPC)has a dismal prognosis.Herein,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and safety.In 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,respectively.Grade 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer PFS.Additionally,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy.In conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC.The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.
基金We thank the National Key R&D Program of China(2021YFA1500100)National Natural Science Foundation of China(21821002,92256302,22071260)Science and Technology Commission of Shanghai Municipality(21520780100)for generous financial support.S.-L.Y.thanks the supports from the New Cornerstone ScienceFoundation.
文摘Rhodium(III)-catalyzed enantioselective C-H indolylization of isoquinolines was developed.The C-H coupling reactions between 1-aryl isoquinoline derivatives and 3-indolylphenyliodonium salts proceeded smoothly in the presence of a modified chiral cyclopentadienyl-Rh(III)complex,affording a series of axially chiral indolylated biaryl products in excellent yields and enantioselectivity(up to 98%yield and 95%ee).
基金supported by the National Key Research and Development Program of China(2021YFA1500100)the National Natural Science Foundation of China(21821002,92256302,22071260)the Science and Technology Commission of Shanghai Municipality(21520780100)。
文摘Chiral dihydrobenzofuran is a valuable synthetic fragment in both medicinal and organic chemistry.Efficient rhodium(Ⅲ)-catalyzed chemoselective and enantioselective C-H functionalization/[3+2]annulation of N-phenoxyacetamides with 1,3-dienes is reported.In the presence of 5 mol%Cp Rh complex,various chiral dihydrobenzofurans were synthesized in up to 79%yield and 98%ee.This reaction proceeds under mild conditions with excellent functional group compatibility.
