BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and dea...BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and death.While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophy-siology of frailty,direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.AIM Seven electronic databases(China National Knowledge Infrastructure,VIP,SinoMed,Wanfang,PubMed,Web of Science and EMBASE)were searched for articles published before October 31,2023 to identify observational studies that compared the microbiomes of older adults with and without frailty.The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults.The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.RESULTS Eleven observational studies with 912 older adults were included in this review.Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults,with a significant decrease inαdiversity and a significant increase inβdiversity in frail older adults.The pooled results revealed that at the phylum level,four microbiota(Actinobacteria,Proteo-bacteria,Verrucomicrobia and Synergistetes)were significantly enriched,and two microbiota(Firmicutes and Fusobacteria)were significantly depleted in frail older adults.At the family level,the results consistently revealed that the abundances of 6 families,most of which belong to the Actinobacteria or Proteo-bacteria phylum,were greater in frail than in non-frail older adults.At the genus or species level,consistent results from more than two studies revealed that the abundances of the genera Prevotella,Faecalibacterium,and Roseburia were significantly lower in frail older adults;individual studies revealed that the abundances of some genera or species(e.g.,Megamonas,Blautia,and Megasphaera)were significantly lower,whereas those of other genera or species(e.g.,Bifidobacterium,Oscillospira,Ruminococcus and Pyramidobacter)were significantly greater in frail older adults.CONCLUSION This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults,which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species.However,further studies are needed to confirm these findings.展开更多
Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure ...Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains unknown.Whole-exome sequencing(WES)was performed to identify candidate mutations in couples with primary infertility.Sanger sequencing was used to validate the mutations.Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced.Assisted oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte activation.We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,p.R385Q.PN formation failure was observed during the ICSI cycle.However,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN formation.AOA after ICSI enabled normal fertilization,and all patients achieved successful pregnancies.These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy.Furthermore,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.展开更多
To the Editor:Adams-Oliver syndrome (AOS,including 6 types) was initially reported in a three-generation family by Adams and Oliver in 1945,[1] with an estimated incidence of 1 in 225,000 live births.[2] Approximately...To the Editor:Adams-Oliver syndrome (AOS,including 6 types) was initially reported in a three-generation family by Adams and Oliver in 1945,[1] with an estimated incidence of 1 in 225,000 live births.[2] Approximately 84% of AOS patients have terminal transverse limb defects,including amputations,syndactyly,brachydactyly,or oligodactyly.展开更多
文摘BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and death.While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophy-siology of frailty,direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.AIM Seven electronic databases(China National Knowledge Infrastructure,VIP,SinoMed,Wanfang,PubMed,Web of Science and EMBASE)were searched for articles published before October 31,2023 to identify observational studies that compared the microbiomes of older adults with and without frailty.The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults.The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.RESULTS Eleven observational studies with 912 older adults were included in this review.Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults,with a significant decrease inαdiversity and a significant increase inβdiversity in frail older adults.The pooled results revealed that at the phylum level,four microbiota(Actinobacteria,Proteo-bacteria,Verrucomicrobia and Synergistetes)were significantly enriched,and two microbiota(Firmicutes and Fusobacteria)were significantly depleted in frail older adults.At the family level,the results consistently revealed that the abundances of 6 families,most of which belong to the Actinobacteria or Proteo-bacteria phylum,were greater in frail than in non-frail older adults.At the genus or species level,consistent results from more than two studies revealed that the abundances of the genera Prevotella,Faecalibacterium,and Roseburia were significantly lower in frail older adults;individual studies revealed that the abundances of some genera or species(e.g.,Megamonas,Blautia,and Megasphaera)were significantly lower,whereas those of other genera or species(e.g.,Bifidobacterium,Oscillospira,Ruminococcus and Pyramidobacter)were significantly greater in frail older adults.CONCLUSION This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults,which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species.However,further studies are needed to confirm these findings.
基金the General Project of Chongqing Natural Science foundation of China(cstc2021jcyj-msxmX0877)the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau,2023MSXM054)the General Project of Chongqing Health Center for Women and Children(2020YJMS01 and 2021YJMS05).
文摘Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains unknown.Whole-exome sequencing(WES)was performed to identify candidate mutations in couples with primary infertility.Sanger sequencing was used to validate the mutations.Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced.Assisted oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte activation.We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,p.R385Q.PN formation failure was observed during the ICSI cycle.However,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN formation.AOA after ICSI enabled normal fertilization,and all patients achieved successful pregnancies.These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy.Furthermore,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.
文摘To the Editor:Adams-Oliver syndrome (AOS,including 6 types) was initially reported in a three-generation family by Adams and Oliver in 1945,[1] with an estimated incidence of 1 in 225,000 live births.[2] Approximately 84% of AOS patients have terminal transverse limb defects,including amputations,syndactyly,brachydactyly,or oligodactyly.
