BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signalin...The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, mi R-103-3 p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that mi R-103-3 p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, mi R-103-3 p negatively regulated Nud E neurodevelopment protein 1-like 1(Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3 a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel mi R-103-3 p target and that mi R-103-3 p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China(approval No. 20200826-003) on August 26, 2020.展开更多
hydrocarbon belts due to their potential applications in carbon nanotechnology.By contrast,heteroatomembedded zigzag hydrocarbon belts as advanced design strategies with fascinating structures and desirable,unique pro...hydrocarbon belts due to their potential applications in carbon nanotechnology.By contrast,heteroatomembedded zigzag hydrocarbon belts as advanced design strategies with fascinating structures and desirable,unique properties have remained largely unexplored,and inherently chiral ones are unknown.Herein,we report the synthesis of a diversity of symmetric and highly enantiopure inherently chiral O-and N-doped zigzag-type hydrocarbon belts starting from strainless macrocycles based on fjord-stitching strategy.The readily available pertriflated resorcin[6]arene underwent partial hydrolyses and intramolecular S_(N)Ar reactions to form a calix[3](9H-xanthene)derivative and a prochiral half-belt selectively.Straightforward transformations of calix[3](9H-xanthene)into C_(3v)-symmetric molecular belts were achieved by closing the rest of the fjords with triple intramolecular S_(N)Ar reactions and Yamamoto homo coupling reactions,as well as palladiumcatalyzed intermolecular acridination reactions with primary amines.The prochiral half-belt underwent enantioselective desymmetrizative mono-acridination to afford an inherently chiral N,O_(4)-bridged pseudo-belt with an enantiomeric excess(ee)value of>99%under the catalysis of Pd(OAc)_(2)and(R)-Antphos.Ring closure reactions of the pseudo-belt produced diverse heteroatom-inlayed zigzag-type hydrocarbon belts of inherent chirality.Further,we showed the unique cavity structures of the belts and demonstrated interesting chiroptic properties of the inherently enantiopure chiral belts.This research opens the door for the exploration of novel and sophisticated symmetric and inherently chiral molecular nanobelt structures with outstanding physical and chemical properties,as well as potential applications.展开更多
Postharvest pathogens can affect a wide range of fresh fruit and vegetables,including grapes,resulting in significant profit loss.Isoquinoline alkaloids of Mahonia fortunei,a Chinese herbal medicine,have been used to ...Postharvest pathogens can affect a wide range of fresh fruit and vegetables,including grapes,resulting in significant profit loss.Isoquinoline alkaloids of Mahonia fortunei,a Chinese herbal medicine,have been used to treat infectious microbes,which might be effective against postharvest pathogens.The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids,of which 9 compounds inhibited the growth of Botrytis cinerea and 4 compounds against Penicillium italicum.The antifungal alkaloids could change the mycelium morphology,the total lipid content,and leak the cell contents of B.cinerea.Furthermore,the two most potent antifungal alkaloids,berber-ine(13)completely inhibited effect on gray mold of table grape at 512 mg L^(−1),while jatrorrhizine(18)exhibited an inhibition rate>90%on grape rot at the same concentration,with lower cytotoxicity and residue than chlorothalonil,which suggested that ingredients of M.fortunei might be a low-toxicity,low-residue,eco-friendly botanical fungicide against postharvest pathogens.展开更多
Background Hyperprolactinaemia is a common antipsychotic(AP)-induced adverse effect,particularly in female patients.Aims This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-...Background Hyperprolactinaemia is a common antipsychotic(AP)-induced adverse effect,particularly in female patients.Aims This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-related hyperprolactinaemia in patients with first-episode schizophrenia.Methods PubMed,PsycINFO,EMBASE,Cochrane Library,WanFang and China Journal Net databases were searched to identify eligible randomised controlled trials(RCTs).Primary outcomes were the reductions of serum prolactin level and prolactin-related symptoms.Data were independently extracted by two reviewers and analysed using RevMan(V.5.3).Weighted/standardised mean differences(WMDs/SMDs)±95%Cis were reported.Results In the five RCTs(n=400),the adjunctive aripiprazole(n=197)and the control groups(n=203)with a mean of 11.2 weeks of treatment duration were compared.The aripiprazole group had a significantly lower endpoint serum prolactin level in all patients(five RCTs,n=385;WMD:-50.43 ng/mL(95%Cl:-75.05 to-25.81),p<0.00001;l2=99%),female patients(two RCTs,n=186;WMD:-22.58 ng/mL(95%Cl:-25.67 to-19.49),p<0.00001;l2=0%)and male patients(two RCTs,n=127;WMD:-68.80 ng/mL(95%Cl:-100.11 to-37.49),p<0.0001).In the sensitivity analysis for the endpoint serum prolactin level in all patients,the findings remained significant(p<0.00001;l2=96%).The aripiprazole group was s叩erior to the control group in improving negative symptoms as assessed by the Positive and Negative Syndrome Scale(three RCTs,n=213;SMD:-0.51(95%Cl:-0.79 to-0.24),p=0.0002;l2=0%).Adverse effects and discontinuation rates were similar between the two groups.Conclusions Adjunctive aripiprazole appears to be associated with reduced AP-induced hyperprolactinaemia and improved prolactin-related symptoms in first-episode schizophrenia.Further studies with large sample sizes are needed to confirm these findings.展开更多
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
基金supported by Graduate Scientific Research Innovation Program of Jiangsu Province of China,No.KYCX192066(to WL)Project Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education institutions China,No.03081023(to GHJ)。
文摘The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, mi R-103-3 p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that mi R-103-3 p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, mi R-103-3 p negatively regulated Nud E neurodevelopment protein 1-like 1(Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3 a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel mi R-103-3 p target and that mi R-103-3 p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China(approval No. 20200826-003) on August 26, 2020.
基金supported by the National Natural Science Foundation of China(NSFC,grant nos.22050005,21920102001,22171160,and 22371161)Tsinghua University Dushi Program,and China National Postdoctoral Program for Innovative Talents(grant no.BX20220184).
文摘hydrocarbon belts due to their potential applications in carbon nanotechnology.By contrast,heteroatomembedded zigzag hydrocarbon belts as advanced design strategies with fascinating structures and desirable,unique properties have remained largely unexplored,and inherently chiral ones are unknown.Herein,we report the synthesis of a diversity of symmetric and highly enantiopure inherently chiral O-and N-doped zigzag-type hydrocarbon belts starting from strainless macrocycles based on fjord-stitching strategy.The readily available pertriflated resorcin[6]arene underwent partial hydrolyses and intramolecular S_(N)Ar reactions to form a calix[3](9H-xanthene)derivative and a prochiral half-belt selectively.Straightforward transformations of calix[3](9H-xanthene)into C_(3v)-symmetric molecular belts were achieved by closing the rest of the fjords with triple intramolecular S_(N)Ar reactions and Yamamoto homo coupling reactions,as well as palladiumcatalyzed intermolecular acridination reactions with primary amines.The prochiral half-belt underwent enantioselective desymmetrizative mono-acridination to afford an inherently chiral N,O_(4)-bridged pseudo-belt with an enantiomeric excess(ee)value of>99%under the catalysis of Pd(OAc)_(2)and(R)-Antphos.Ring closure reactions of the pseudo-belt produced diverse heteroatom-inlayed zigzag-type hydrocarbon belts of inherent chirality.Further,we showed the unique cavity structures of the belts and demonstrated interesting chiroptic properties of the inherently enantiopure chiral belts.This research opens the door for the exploration of novel and sophisticated symmetric and inherently chiral molecular nanobelt structures with outstanding physical and chemical properties,as well as potential applications.
基金NSFC,32170405,Xiao-Dong Luothe High-level Talent Promotion and Training Project of Kunming,2022SCP003,Xiao-Dong Luo+1 种基金Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform,2022YKZY001,Xiao-Dong LuoScientific and Technological Innovation Team of Yunnan Province,202105AE160006,Xiao-Dong Luo.
文摘Postharvest pathogens can affect a wide range of fresh fruit and vegetables,including grapes,resulting in significant profit loss.Isoquinoline alkaloids of Mahonia fortunei,a Chinese herbal medicine,have been used to treat infectious microbes,which might be effective against postharvest pathogens.The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids,of which 9 compounds inhibited the growth of Botrytis cinerea and 4 compounds against Penicillium italicum.The antifungal alkaloids could change the mycelium morphology,the total lipid content,and leak the cell contents of B.cinerea.Furthermore,the two most potent antifungal alkaloids,berber-ine(13)completely inhibited effect on gray mold of table grape at 512 mg L^(−1),while jatrorrhizine(18)exhibited an inhibition rate>90%on grape rot at the same concentration,with lower cytotoxicity and residue than chlorothalonil,which suggested that ingredients of M.fortunei might be a low-toxicity,low-residue,eco-friendly botanical fungicide against postharvest pathogens.
文摘Background Hyperprolactinaemia is a common antipsychotic(AP)-induced adverse effect,particularly in female patients.Aims This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-related hyperprolactinaemia in patients with first-episode schizophrenia.Methods PubMed,PsycINFO,EMBASE,Cochrane Library,WanFang and China Journal Net databases were searched to identify eligible randomised controlled trials(RCTs).Primary outcomes were the reductions of serum prolactin level and prolactin-related symptoms.Data were independently extracted by two reviewers and analysed using RevMan(V.5.3).Weighted/standardised mean differences(WMDs/SMDs)±95%Cis were reported.Results In the five RCTs(n=400),the adjunctive aripiprazole(n=197)and the control groups(n=203)with a mean of 11.2 weeks of treatment duration were compared.The aripiprazole group had a significantly lower endpoint serum prolactin level in all patients(five RCTs,n=385;WMD:-50.43 ng/mL(95%Cl:-75.05 to-25.81),p<0.00001;l2=99%),female patients(two RCTs,n=186;WMD:-22.58 ng/mL(95%Cl:-25.67 to-19.49),p<0.00001;l2=0%)and male patients(two RCTs,n=127;WMD:-68.80 ng/mL(95%Cl:-100.11 to-37.49),p<0.0001).In the sensitivity analysis for the endpoint serum prolactin level in all patients,the findings remained significant(p<0.00001;l2=96%).The aripiprazole group was s叩erior to the control group in improving negative symptoms as assessed by the Positive and Negative Syndrome Scale(three RCTs,n=213;SMD:-0.51(95%Cl:-0.79 to-0.24),p=0.0002;l2=0%).Adverse effects and discontinuation rates were similar between the two groups.Conclusions Adjunctive aripiprazole appears to be associated with reduced AP-induced hyperprolactinaemia and improved prolactin-related symptoms in first-episode schizophrenia.Further studies with large sample sizes are needed to confirm these findings.
