AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study...AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study(GWAS)were used.Inverse variance weighted(IVW)analysis and sensitivity analysis were performed on the FinnGen project,which included 5095 cases and 222590 controls.RESULTS:The IVW analysis showed substantial genusand family-level relationships between GM taxa and dAMD risk.Specifically,the family Peptococcaceae(P=0.03),genus Bilophila(P=3.91×10^(-3)),genus Faecalibacterium(P=6.55×10^(-3)),and genus Roseburia(P=0.04)were linked to a higher risk of developing dAMD,while the genus Candidatus Soleaferrea(P=7.75×10^(-4)),genus Desulfovibrio(P=0.04)and genus Eubacterium ventriosum group(P=0.04)exhibited a protective effect against dAMD.No significant causal relationships were observed at higher taxonomic levels.Additionally,in the reverse IVW analysis,no meaningful causal effects of the 7 GM taxa.CONCLUSION:These findings give support for the gutretina axis participation in dAMD and shed light on putative underlying processes.Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.展开更多
Age-related cataract （ARC） is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. Howev...Age-related cataract （ARC） is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms （SNPs）. No SNPs reached exome-wide significance level of association （P 〈 l x 10 6）. B3GNT4 rs7136356 showed the most significant association with ARC （P = 6.54x 10 5）. Two loci （MUC16 and P2RY2） among the top 20 ARC-associated SNPs were recognized as probably linked to cata- ractogenesis. Functions of these genes were potentially related to regulating dehydration or homeostasis of the eyes, and showed a potential association with dry eye disease. This finding suggests that mucin- and dry eye disease-related genes may play a significant role in cataractogenesis. Our study provides insight into the genetic predisposition of ARC in Koreans. Additional studies with larger sample sizes are required to confirm the results of this study.展开更多
Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have re...Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have reported the association between the serotonin receptor family （5-HTR） gene polymorphisms and ADHD, but the results are still controversial. In this study, we conducted a meta-analysis of the association between 5-HTRIB, 5-HTR2A, and 5-HTR2C genetic variants and ADHD. The results showed that the 861G allele of 5-HTRIB SNP rs6296 could significantly increase the risk of ADHD （OR= 1.09, 95% CI： 1.01-1.18）; the 5-HTR2C gene rs518147 （OR=1.69, 95% CI： 1.38-2.07） and rs3813929 （OR = 1.57, 95% CI： 1.25-1.97） were all associated with the risk of ADHD. In addition, we also carried on a case- control study to explore the relevance between potential candidate genes 5-HTR1A, 5-HTRIE, 5-HTR3A and ADHD. The results indicated that 5-HTRIA rs6295 genotype （CC＋CG vs. GG OR=Z00, 95% CI： 1.23-3.27） and allele （OR=1.77, 95% CI： 1.16-2.72） models were statistically significantly different between case group and control group. This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD, and it also provides more evidence for the etiology of ADHD.展开更多
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related ...The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.展开更多
Dramatic advances in retinal imaging technology over the last two decades have significantly improved our understanding of the natural history and pathophysiology of non-neovascular age-related macular degeneration(AM...Dramatic advances in retinal imaging technology over the last two decades have significantly improved our understanding of the natural history and pathophysiology of non-neovascular age-related macular degeneration(AMD).Currently,aside from micronutrient supplements,there are no proven treatments for non-neovascular or dry AMD.Recently,a number of pharmacological agents have been evaluated or are under evaluation for treatment of patients with end-stage dry AMD manifesting as geographic atrophy(GA).It may preferable,however,to intervene earlier in the disease before the development of irreversible loss of visual function.Earlier intervention would require a more precise understanding of biomarkers which may increase the risk of progression from early and intermediate stages to the late stage of the disease.The development of optical coherence tomography angiography(OCTA)has allowed the layers of the retinal microcirculation and choriocapillaris(CC)to be visualized and quantified.Flow deficits in the CC have been observed to increase with age,particularly centrally,and these flow deficits appear to worsen with development and progression of AMD.As such,OCTA-based CC assessment appears to be a valuable new biomarker in our assessment and risk-stratification of AMD.Alterations in the CC may also provide new insights into the pathophysiology of the disease.Enhancement of choriocapillaris function may also prove to be a target of future therapeutic strategies or as a biomarker to monitor the effectiveness of therapy.As such,CC imaging may be anticipated to be an integral tool in the management of dry AMD.展开更多
Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we p...Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui（GV20） and Taiyang（EX-HN5）. We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave（Hmax/Mmax）, muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of ＂Deficiency and Excess＂. The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was 〉 0 or 〈 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.展开更多
The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using...The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using electrocoagulation, The rats were intrapedtoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week, Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.展开更多
Background:Neovascular age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)are sight-threatening maculopathies with both environmental and genetic risk factors.We have previously shown relat...Background:Neovascular age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)are sight-threatening maculopathies with both environmental and genetic risk factors.We have previously shown relative risks posed by genes of the complement pathways to neovascular AMD and PCV.Methods:In this study,we investigated the haplotype-tagging single nucleotide polymorphisms(SNPs)in the complement component 5(C5)gene in 708 unrelated Chinese individuals:200 neovascular AMD patients,233 PCV patients and 275 controls.Six tagging SNPs in C5 were genotyped.Univariate single SNP association analysis,haplotype-based association analysis and gene-gene interaction analysis between C5 and other AMD-associated genes were performed.Results:The results revealed none of the six tagging SNPs of the C5 gene had a significant association with neovascular AMD or PCV(P>0.05).We also found insignificant haplotype-based association,and no significant SNPSNP interaction between C5 and other genes(including C2-CFB-RDBP-SKIV2L,SERPING1,CETP,ABCG1,PGF,ANGPT2,CFH and HTRA1)for neovascular AMD and PCV.Conclusions:This study showed no statistical significance in the genetic association of C5 with neovascular AMD or PCV in a Hong Kong Chinese population.Further studies in large samples from different populations are warranted to elucidate the role of C5 in the genetic susceptibility of AMD and PCV.展开更多
基金Supported by the Natural Science Foundation of Hunan Province(No.2024JJ6609)the Postdoctoral Fellowship Program of CPSF(No.GZC20233180).
文摘AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study(GWAS)were used.Inverse variance weighted(IVW)analysis and sensitivity analysis were performed on the FinnGen project,which included 5095 cases and 222590 controls.RESULTS:The IVW analysis showed substantial genusand family-level relationships between GM taxa and dAMD risk.Specifically,the family Peptococcaceae(P=0.03),genus Bilophila(P=3.91×10^(-3)),genus Faecalibacterium(P=6.55×10^(-3)),and genus Roseburia(P=0.04)were linked to a higher risk of developing dAMD,while the genus Candidatus Soleaferrea(P=7.75×10^(-4)),genus Desulfovibrio(P=0.04)and genus Eubacterium ventriosum group(P=0.04)exhibited a protective effect against dAMD.No significant causal relationships were observed at higher taxonomic levels.Additionally,in the reverse IVW analysis,no meaningful causal effects of the 7 GM taxa.CONCLUSION:These findings give support for the gutretina axis participation in dAMD and shed light on putative underlying processes.Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.
文摘Age-related cataract （ARC） is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms （SNPs）. No SNPs reached exome-wide significance level of association （P 〈 l x 10 6）. B3GNT4 rs7136356 showed the most significant association with ARC （P = 6.54x 10 5）. Two loci （MUC16 and P2RY2） among the top 20 ARC-associated SNPs were recognized as probably linked to cata- ractogenesis. Functions of these genes were potentially related to regulating dehydration or homeostasis of the eyes, and showed a potential association with dry eye disease. This finding suggests that mucin- and dry eye disease-related genes may play a significant role in cataractogenesis. Our study provides insight into the genetic predisposition of ARC in Koreans. Additional studies with larger sample sizes are required to confirm the results of this study.
文摘Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have reported the association between the serotonin receptor family （5-HTR） gene polymorphisms and ADHD, but the results are still controversial. In this study, we conducted a meta-analysis of the association between 5-HTRIB, 5-HTR2A, and 5-HTR2C genetic variants and ADHD. The results showed that the 861G allele of 5-HTRIB SNP rs6296 could significantly increase the risk of ADHD （OR= 1.09, 95% CI： 1.01-1.18）; the 5-HTR2C gene rs518147 （OR=1.69, 95% CI： 1.38-2.07） and rs3813929 （OR = 1.57, 95% CI： 1.25-1.97） were all associated with the risk of ADHD. In addition, we also carried on a case- control study to explore the relevance between potential candidate genes 5-HTR1A, 5-HTRIE, 5-HTR3A and ADHD. The results indicated that 5-HTRIA rs6295 genotype （CC＋CG vs. GG OR=Z00, 95% CI： 1.23-3.27） and allele （OR=1.77, 95% CI： 1.16-2.72） models were statistically significantly different between case group and control group. This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD, and it also provides more evidence for the etiology of ADHD.
文摘The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.
文摘Dramatic advances in retinal imaging technology over the last two decades have significantly improved our understanding of the natural history and pathophysiology of non-neovascular age-related macular degeneration(AMD).Currently,aside from micronutrient supplements,there are no proven treatments for non-neovascular or dry AMD.Recently,a number of pharmacological agents have been evaluated or are under evaluation for treatment of patients with end-stage dry AMD manifesting as geographic atrophy(GA).It may preferable,however,to intervene earlier in the disease before the development of irreversible loss of visual function.Earlier intervention would require a more precise understanding of biomarkers which may increase the risk of progression from early and intermediate stages to the late stage of the disease.The development of optical coherence tomography angiography(OCTA)has allowed the layers of the retinal microcirculation and choriocapillaris(CC)to be visualized and quantified.Flow deficits in the CC have been observed to increase with age,particularly centrally,and these flow deficits appear to worsen with development and progression of AMD.As such,OCTA-based CC assessment appears to be a valuable new biomarker in our assessment and risk-stratification of AMD.Alterations in the CC may also provide new insights into the pathophysiology of the disease.Enhancement of choriocapillaris function may also prove to be a target of future therapeutic strategies or as a biomarker to monitor the effectiveness of therapy.As such,CC imaging may be anticipated to be an integral tool in the management of dry AMD.
基金supported by a grant from the Supporting Program of the"Eleventh Five-year Plan"for Science&Technology Research of China,Ministry of Science and Technology of China,No.2006BAI12B02a grant from the Scientific Research Fund for Talent Introduction in the Gansu University of Chinese Medicine of China,No.2012-11
文摘Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui（GV20） and Taiyang（EX-HN5）. We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave（Hmax/Mmax）, muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of ＂Deficiency and Excess＂. The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was 〉 0 or 〈 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.
基金the National Natural Science Foundation of China, No. 81073084the Fundamental Research Funds for the Central Universities, No.XDJK2009C081+1 种基金the Natural Science Foundation Project of CQ CSTC, No.2010BB5127Science and Technology Innovative Capacity Construction Program of Chongqing(CSTC) No.2009CB1010
文摘The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using electrocoagulation, The rats were intrapedtoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week, Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.
基金supported in part by the General Research Fund,Hong Kong(14120516[LJC])the Direct Grant of Chinese University of Hong Kong Medical Panel,Hong Kong(4054281[LJC])the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre,Hong Kong.
文摘Background:Neovascular age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)are sight-threatening maculopathies with both environmental and genetic risk factors.We have previously shown relative risks posed by genes of the complement pathways to neovascular AMD and PCV.Methods:In this study,we investigated the haplotype-tagging single nucleotide polymorphisms(SNPs)in the complement component 5(C5)gene in 708 unrelated Chinese individuals:200 neovascular AMD patients,233 PCV patients and 275 controls.Six tagging SNPs in C5 were genotyped.Univariate single SNP association analysis,haplotype-based association analysis and gene-gene interaction analysis between C5 and other AMD-associated genes were performed.Results:The results revealed none of the six tagging SNPs of the C5 gene had a significant association with neovascular AMD or PCV(P>0.05).We also found insignificant haplotype-based association,and no significant SNPSNP interaction between C5 and other genes(including C2-CFB-RDBP-SKIV2L,SERPING1,CETP,ABCG1,PGF,ANGPT2,CFH and HTRA1)for neovascular AMD and PCV.Conclusions:This study showed no statistical significance in the genetic association of C5 with neovascular AMD or PCV in a Hong Kong Chinese population.Further studies in large samples from different populations are warranted to elucidate the role of C5 in the genetic susceptibility of AMD and PCV.
