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Gonadotropin releasing hormone(GnRH):a hormone therapy boosts cognition in down syndrome and dementia

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Signal Transduction and Targeted Therapy 2023年第3期8卷 869-871页

作者： Keenan Sterling Ruixue Cao Weihong Song Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBCCanada The Second Affiliated Hospital and Yuying Children’s Hospital Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhouChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouChina

A recent study published in Science by Manfredi-Lozano and colleagues suggests that the gonadotropin-releasing hormone(GnRH)could potentially restore cognition in patients with down syndrome(DS).1 The findings reveal a new molecular link between dementia and the loss of smell,and a promising therapeutic avenue to combat age-related cognitive decline in DS and other neurodegenerative diseases.

关键词： releasing down boost

down syndrome child with multiple heart diseases: A case report

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World Journal of Cardiology 2023年第11期15卷 615-622页

作者： Mo-Wei Kong Yi-Jing Li Jun Li Zhen-Ying Pei Yu-Yu Xie Guo-Xiang He Department of Cardiology Guiqian International General HospitalGuiyang 550018Guizhou ProvinceChina Department of Dermatology Guiqian International General HospitalGuiyang 550018Guizhou ProvinceChina

BACKGROUND down syndrome,also known as trisomy 21 syndrome,is commonly associated with congenital heart disease,and can often result in early formation of pulmonary hypertension.The development of pulmonary hypertension can result from factors such as intracardiac and macrovascular shunts,and upper airway obstruction or hypoplasia of lung tissue.Individuals with down syndrome and congenital heart disease have a significantly lower average life expectancy,with surgical intervention being the most viable treatment option to improve longevity.CASE SUMMARY We report the case of a 13-year-old boy with down syndrome presenting with atrial septal defect and patent ductus arteriosus along with severe pulmonary hypertension.The electrocardiogram shows sinus rhythm and right ventricular hypertrophy.The echocardiogram shows an atrial septal defect with interrupted echo in the interatrial septum,measuring 0.813 cm in length.The patient was initially refused to be offered surgical treatment by many hospitals due to the high surgical risk and pulmonary artery resistance.After discussing the patient’s diagnosis and treatment options,we ultimately recommended surgical treatment.However,the patient and their family declined this recommendation and chose to be discharged.During the follow-up period of 6 mo,there were no significant improvements or deteriorations in the patient’s condition.CONCLUSION In conclusion,this case highlights the challenges faced by individuals with down syndrome and congenital heart disease complicated by severe pulmonary hypertension.Timely intervention and a multidisciplinary approach are crucial for improving prognosis and life expectancy.Further research is needed to enhance our understanding and develop effective interventions for this popula-tion.Core Tip:This case study presents a 13-year-old boy diagnosed with down syndrome alongside atrial septal defect,patent ductus arteriosus,and severe pulmonary hypertension.A complex condition initially met with surgical treatment denial due to high risks,hig

关键词： down initially holds

TDF Promotes Glycolysis and Mitochondrial Dysfunction to Accelerate Lactate Accumulation by downregulating PGC1α in Mice

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 998-1002页

作者： Yuxuan Luo Zhiwei Chen Zhao Li Aoran Luo Yi Zeng Min Chen Mingli Peng Hong Ren Peng Hu Department of Infectious Diseases Institute for Viral HepatitisThe Key Laboratory of Molecular Biology for Infectious DiseasesChinese Ministry of EducationThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Internal Medicine(Cardiology) University of Texas Southwestern Medical CenterDallasTexasUSA

Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatitis B virus(HBV)infection.Hence,a better understanding of the safety profiles of long-term TDF use is extremely important.Lactic acidosis,as a rare but fatal adverse event of TDF,were reported both in HIV-infected patients,2-4 and in CHB patients.5-7 Hyperlactatemia occurred in 15.6%HIV-infected patients using TDF in a Cameroon cohort study8 and was 3%in another South Africa cohort study.9 Therefore,TDF increases the risk of abnormal serum lactate,but the mechanism is unclear.

关键词： PGC1α down Africa

downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP

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Journal of Geriatric Cardiology 2021年第6期18卷 426-439页

作者： You ZHOU Man-Yun LONG Zhi-Qing CHEN Jun-Wen HUANG Zhen-Bai QIN Lang LI Department of Cardiology the First Affiliated Hospital of Guangxi Medical UniversityNanningChina Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention NanningChina

BACKGROUND Coronary microembolization(CME)is a complicated problem that commonly arises in the context of coronary angioplasty.MicroRNAs play crucial roles in cardiovascular diseases.However,the role and mechanism of miR-181a-5p in CME-induced myocardial injury remains unclear.METHODS We established CME rat models.Cardiac function was detected by echocardiography.Haematoxylin-basic fuchsin-picric acid staining was used to measure micro-infarction size.Serum samples and cell culture supernatants were evaluated via enzyme-linked immunosorbent assay.Cellular reactive oxygen species were determined by dichloro-dihydro-fluorescein diacetate assay,and the other oxidative stress related parameters were assayed by spectrophotometry.The dual-luciferase reporter(DLR)assay and RNA pulldown were conducted to validate the association between miR-181a-5p and X-linked inhibitor of apoptosis protein(XIAP).The expression of miR-181a-5p and XIAP mRNA were determined by quantitative reverse transcription polymerase chain reaction.Proteins were evaluated via immunoblotting.The viability of the cell was evaluated via cell counting kit-8 assay.RESULTS The miR-181a-5p level was significantly increased in CME myocardial tissues.downregulation of miR-181a-5p improved CME-induced cardiac dysfunction and alleviated myocardial oxidative stress and inflammatory injury,whereas miR-181a-5p exhibited the opposite effects.Then,the DLR assay and RNA pulldown results revealed that miR-181a-5p directly targeting on XIAP.The XIAP level was found to be remarkably decreased after CME.XIAP overexpression attenuated CME-induced myocardial oxidative stress and inflammatory injury.Finally,in vitro rescue experiments revealed that knockdown of XIAP could abolish the protective effects of miR-181a-5p knockdown on hypoxia-induced cardiomyocyte oxidative stress and inflammatory injury.CONCLUSIONS downregulation of miR-181a-5p alleviates CME-induced myocardial damage by suppressing myocardial oxidative stress and inflammation through directly targeting XIAP.

关键词： damage XIAP down

Luteolin induces hippocampal neurogenesis in the Ts65Dn mouse model of down syndrome

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Neural Regeneration Research 2019年第4期14卷 613-620页

作者： Wen-Bo Zhou Zong-Ning Miao Bin Zhang Wei Long Fang-Xiu Zheng Jing Kong Bin Yu Changzhou Women and Children Health Hospital Affiliated to Nanjing Medical University The Stem Cell Research Laboratory Wuxi Third People's Hospital

Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of down syndrome. Ts65 Dn mice, which are frequently used as a model of down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neurotrophic factor(BDNF) and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX^+ neurons in the granular layer and NeuN^+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65 Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.

关键词： nerve regeneration luteolin hippocampus Ts65Dn mice neurogenesis ERK BDNF nestin GFAP NeuN down syndrome neural regeneration

Understanding and breaking down the reproductive barrier between Asian and African cultivated rice: a new start for hybrid rice breeding

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Science China(Life Sciences) 2019年第8期62卷 1114-1116页

作者： Yidan Ouyang National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research (Wuhan) Huazhong Agricultural University

Oryza sativa and O.glaberrima,commonly known as Asian and African cultivated rice,are two domesticated rice species in Oryza genus.Asian cultivated rice may produce higher yields with better quality,whereas African cultivated rice shows a wide range of tolerance to abiotic and biotic stresses.Interspecific hybrids between O.sativa and O.glaberrima would show strong heterosis and thus increasing production because of their distant genetic diversity and complementary agronomic traits.However,reduced fertility is observed in hybrids from interspecific crosses;this hinders further utilization of rice heterosis in agriculture production.Such severe abnormal development of gametophytes in hybrids is caused by reproductive isolation,a process that prevents individuals of genetically diverged groups from mating,survival or producing fertile offspring.

关键词： TPR Understanding and breaking down the reproductive barrier between Asian and African cultivated rice a new start for hybrid rice breeding

A population-based study of prevalence of down syndrome in Southern Thailand

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World Journal of Pediatrics 2017年第1期13卷 63-69页

作者： Somchit Jaruratanasirikul Ounjai Kor-anantakul Montira Chowvichian Wannee Limpitikul Pathikan Dissaneevate Nitthakarn Intharasangkanawin Atchara Sattapanyo Sermsri Pathompanitrat Faculty of Medicine Prince of Songkla UniversityHat YaiSongkhla 90110Thailand Medical Education Center Songkhla Hospital Medical Education Center Hatyai Hospital Medical Education Center Trang Hospital Phatthalung Hospital

Background:down syndrome(Ds)is the most common chromosomal disorder that causes mental retardatiOn.In 2009,a population-based birth defects study was implemented in three provinces in southern Thailand.This study aimed to determine the prevalence of DS in the studied re-gions,and the proportion of DS fetuses detected by prenatal screening.Metheds?Data were obtained from a populationbased surveillance study undertaken during 2009—2013.Entries in the birth defects registry included live births,stillbirths after 24 weeks gestational age.and terminations of pregnancy following prenatal diagnosis.Infants with clinical characteristics of DS had a chromosomal study to make a definite diagnosis.

关键词： birth defect registry down syndrome prenatal screening termination of pregnancy trisomy 21

Comorbidities in down syndrome livebirths and health care intervention: an initial experience from the birth defects registry in Southern Thailand

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World Journal of Pediatrics 2017年第2期13卷 152-157页

作者： Somchit Jaruratanasirikul Wannee Limpitikul Pathikan Dissaneevate Paveena Booncharoen Pongsak Tantichantakarun Faculty of Medicine Prince of Songkla UniversityHat YaiSongkhlaThailand Medical Education Center Songkhla HospitalSongkhlaThailand Medical Education Center Hatyai HospitalHat YaiSongkhlaThailand Medical Education Center Trang HospitalTrangThailand Phatthalung Hospital PhatthalungThailand

Background:down syndrome (DS) is the most common chromosomal disorder causing mental retardation with a worldwide average prevalence of 1-2 cases per 1000 births.This study aimed to determine the comorbidities associated with DS and the coverage of health care services and developmental interventions for DS iivebirths in Southern Thailand.Methods:A total of 149 livebirth DS infants,recruited through the prospective birth defects registry system during 2009-2013 in 3 provinces in Southern Thailand,were regularly followed-up every 3-6 months.The data collection form included the infants' demographic data,associated congenital anomalies,and developmental interventions.Results:The DS infants were born at an average gestational age of 38.5±2.3 weeks with average birth weight of 2760±478 g,length 48.5±2.2 cm,and head circumference 32.7±1.2 cm.Congenital heart diseases,gastrointestinal defects and congenital hypothyroidism were found in 43.0%,6.7%,and 12.1% of the cases,respectively.The percentage of DS infants who received developmental interventions in this current study were significantly greater than in a previous study covering the years 1992-2002:early stimulation program 90.0% vs.65.6% (P<0.01),and speech training program 74.8% vs.38.9% (P<0.01),respectively,and the infants in our study began intervention programs significantly earlier,0.58±0.39 years vs.1.69±0.66 years,respectively.Conclusions:Congenital heart disease was the most common comorbidity associated with DS.The coverage of health care services and developmental interventions for DS children has generally improved in Southern Thailand.One hundred percent coverage of health services and interventions for children with special needs is expected in the near future.

关键词： developmental intervention down syndrome trisomy 21

Prostate cancer upgrading or downgrading of biopsy Gleason scores at radical prostatectomy:prediction of"regression to the mean"using routine clinical features with correlating biochemical relapse rates

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Asian Journal of Andrology 2019年第6期21卷 598-604页

作者： Muammer Altok Patricia Troncoso Mary F Achim Surena F Matin Graciela N Gonzalez John W Davis Department of Urology University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Pathology University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Biostatistics University of Texas MD Anderson Cancer CenterHoustonTX 77030USA.

Recommendations for managing clinically localized prostate cancer are structured around clinical risk criteria,with prostate biopsy(PB)Gleason score(GS)being the most important factor.Biopsy to radical prostatectomy(RP)specimen upgrading/downgrading is welldescribed,and is often the ratio nale for costly imaging or genomic studies.We prese nt simple,no-cost an a lyses of clinical parametersto predict which GS 6 and GS 8 patients will change to GS 7 at prostatectomy.From May 2006 to December 2012,1590 patientsunderwent robot-assisted radical prostatectomy(RARP).After exclusions,we identified a GS 6 cohort of 374 patients and a GS 8cohort of 91 patients.During this era,>1000 additional patients were enrolled in an active surveillanee(AS)program.For GS 6,265(70.9%)of 374 patients were upgraded,and the cohort included 183(48.9%)patients eligible for AS by the Prostate Cancer ResearchInternational Active Surveillance Study(PRIAS)standards,of which 57.9%were upgraded.PB features that predicted a>90%chanceof upgrading included≥7 cores positive,maximum foci length≥8 mm in any core,and total tumor involvement≥30%.For GS 8,downgrading occurred in 46(50.5%),which was significantly higher for single core versus multiple cores(80.4%vs 19.6%,P=0.011).Biochemical recurre nee(BCR)occurred in 3.4%of GS 6 upgraded versus 0%non upgraded,and in GS 8,19.6%downgraded versus42.2%nondown graded.In coun seling men with clin ically localized prostate can cer,the odds of GS cha nge should be presented,andcertain men with high-volume GS 6 or low-volume GS 8 can be counseled with GS 7-based recommendations.

关键词： biopsy down grade Gleas on score prostate cancer upgrade