BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and...BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.展开更多
Primordial germ cells(PGCs),the precursors of oocytes and spermatozoa,are highly pluripotent.In recent years,the in vitro induction of human primordial germ cell-like cells(h PGCLCs)has advanced significantly.However,...Primordial germ cells(PGCs),the precursors of oocytes and spermatozoa,are highly pluripotent.In recent years,the in vitro induction of human primordial germ cell-like cells(h PGCLCs)has advanced significantly.However,the stability and efficacy of obtaining h PGCLCs in vitro still require improvement.In the current study,we identified a novel induction system using Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F-12)as the basal medium,supplemented with B27 and N2(referred to as N2B27)in combination with four cytokines:bone morphogenetic protein 4,stem cell factor,epidermal growth factor,and leukemia inhibitory factor.The h PGCLCs induced under these conditions closely resembled PGCs from 4-to 5-week-old embryos at the transcriptomic level.Compared with traditional GK15(GMEM supplemented with 15%Knockout?Serum Replacement)-based induction conditions,the N2B27 system significantly increased the speed and efficacy of h PGCLC induction.RNA sequencing analysis revealed that this improvement was due to an increased cellular capacity to cope with hypoxic stress and avoid apoptosis.The N2B27 medium promoted enhanced mitochondrial activity,enabling cells to better manage hypoxic stress while reducing the production of reactive oxygen species.Moreover,through gradient concentration experiments,we demonstrated that the addition of the common antioxidant N-acetyl-L-cysteine at an optimized concentration further enhanced the efficiency of PGCLC induction under GK15 conditions.In summary,we have established an optimized induction system that enhances the efficiency of h PGCLC differentiation by improving cellular resilience to hypoxic stress and apoptosis.展开更多
文摘BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.
基金funded by the National Key R&D Program(Grant Nos.2022YFC2702800 and 2021YFC2700302 to Y.Y.)the National Natural Science Foundation of China(Grant Nos.82122025 to Y.Y.,82221005 to J.S.,and 82201763 to L.L.)。
文摘Primordial germ cells(PGCs),the precursors of oocytes and spermatozoa,are highly pluripotent.In recent years,the in vitro induction of human primordial germ cell-like cells(h PGCLCs)has advanced significantly.However,the stability and efficacy of obtaining h PGCLCs in vitro still require improvement.In the current study,we identified a novel induction system using Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F-12)as the basal medium,supplemented with B27 and N2(referred to as N2B27)in combination with four cytokines:bone morphogenetic protein 4,stem cell factor,epidermal growth factor,and leukemia inhibitory factor.The h PGCLCs induced under these conditions closely resembled PGCs from 4-to 5-week-old embryos at the transcriptomic level.Compared with traditional GK15(GMEM supplemented with 15%Knockout?Serum Replacement)-based induction conditions,the N2B27 system significantly increased the speed and efficacy of h PGCLC induction.RNA sequencing analysis revealed that this improvement was due to an increased cellular capacity to cope with hypoxic stress and avoid apoptosis.The N2B27 medium promoted enhanced mitochondrial activity,enabling cells to better manage hypoxic stress while reducing the production of reactive oxygen species.Moreover,through gradient concentration experiments,we demonstrated that the addition of the common antioxidant N-acetyl-L-cysteine at an optimized concentration further enhanced the efficiency of PGCLC induction under GK15 conditions.In summary,we have established an optimized induction system that enhances the efficiency of h PGCLC differentiation by improving cellular resilience to hypoxic stress and apoptosis.
