Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex s...Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.展开更多
BACKGROUND Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium.Previously,clinical trials did not reach definite conclusions on the effects of statins on delirium.So...BACKGROUND Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium.Previously,clinical trials did not reach definite conclusions on the effects of statins on delirium.Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes,while some studies have reported negative results.AIM To evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes.METHODS This randomized,double-blind,and placebo-controlled trial was conducted in a single center in Jiangsu,China.This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent.A computer-generated randomization sequence(in a 1:1 ratio)was used to randomly assign patients to receive either rosuvastatin(40 mg/d)or placebo.Participants,care providers,and investigators were all masked to group assignments.The primary endpoint was the incidence of delirium,which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days.Analyses were performed on intention-to-treat and safety populations.RESULTS Between January 1,2017 and January 1,2020,3512 patients were assessed.A total of 821 patients were randomly assigned to receive either placebo(n=411)or rosuvastatin(n=410).The incidence of postoperative delirium was significantly lower in the rosuvastatin group[23(5.6%)of 410 patients]than in the placebo group{42(13.5%)of 411 patients[odds ratios(OR)=0.522,95%confidence interval(CI):0.308-0.885;P<0.05]}.No significant difference in 30-d all-cause mortality(6.1%vs 8.7%,OR=0.67,95%CI:0.39-1.2,P=0.147)was observed between the two groups.Rosuvastatin decreased the hospitalization time(13.8±2.5 vs 14.2±2.8,P=0.03)and hospitalization expenses(9.3±2.5 vs 9.8±2.9,P=0.007).No significant differences in abnormal liver enzymes(9.0%vs 7.1%,OR=1.307,95%CI:0.787-2.169,P=0.30)or rhabdomyolysis(0.73%vs 0.24%,OR=3.020,95%CI:0.31-29.2,P=0.37)were observed between the two groups.CONCLUSION The current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia.However,the evidence does not reveal that rosuvastatin improves clinical outcomes.The therapy is safe.Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.展开更多
基金suppor ted by the National Key Research and Development Program of China(2022YFA1104800)the Beijing Nova Program(20220484100)+6 种基金the National Natural Science Foundation of China(81873939)the Open Research Fund of State Key Laboratory of Cardiovascular Disease,Fuwai Hospital(2022KF-04)the Clinical Medicine Plus X-Young Scholars Projec t,Pek ing Universit y(PKU2022LCXQ003)the Emerging Engineering InterdisciplinaryYoung Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities(PKU2023XGK011)the Open Research Fund of State Key Laboratory of Digital Medical Engineering,Southeast University(2023K-01)the Open Research Fund of Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease,Beijing,China(DXWL2023-01)the Science and Technology Bureau Foundation Application Project of Changzhou(CJ20220118)。
文摘Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.
文摘BACKGROUND Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium.Previously,clinical trials did not reach definite conclusions on the effects of statins on delirium.Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes,while some studies have reported negative results.AIM To evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes.METHODS This randomized,double-blind,and placebo-controlled trial was conducted in a single center in Jiangsu,China.This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent.A computer-generated randomization sequence(in a 1:1 ratio)was used to randomly assign patients to receive either rosuvastatin(40 mg/d)or placebo.Participants,care providers,and investigators were all masked to group assignments.The primary endpoint was the incidence of delirium,which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days.Analyses were performed on intention-to-treat and safety populations.RESULTS Between January 1,2017 and January 1,2020,3512 patients were assessed.A total of 821 patients were randomly assigned to receive either placebo(n=411)or rosuvastatin(n=410).The incidence of postoperative delirium was significantly lower in the rosuvastatin group[23(5.6%)of 410 patients]than in the placebo group{42(13.5%)of 411 patients[odds ratios(OR)=0.522,95%confidence interval(CI):0.308-0.885;P<0.05]}.No significant difference in 30-d all-cause mortality(6.1%vs 8.7%,OR=0.67,95%CI:0.39-1.2,P=0.147)was observed between the two groups.Rosuvastatin decreased the hospitalization time(13.8±2.5 vs 14.2±2.8,P=0.03)and hospitalization expenses(9.3±2.5 vs 9.8±2.9,P=0.007).No significant differences in abnormal liver enzymes(9.0%vs 7.1%,OR=1.307,95%CI:0.787-2.169,P=0.30)or rhabdomyolysis(0.73%vs 0.24%,OR=3.020,95%CI:0.31-29.2,P=0.37)were observed between the two groups.CONCLUSION The current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia.However,the evidence does not reveal that rosuvastatin improves clinical outcomes.The therapy is safe.Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.