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Current methods for the maturation of induced pluripotent stem cellderived cardiomyocytes

World Journal of Stem Cells 2019年第1期11卷 33-43页

作者： Pranav Machiraju Steven C Greenway departments of pediatrics and cardiac sciences Alberta Children’s Hospital Research Institute Libin Cardiovascular Institute of Alberta Cumming School of MedicineUniversity of Calgary departments of pediatrics Cardiac Sciences Biochemistry & Molecular Biology Alberta Children’s Hospital Research Institute Libin Cardiovascular Institute of Alberta Cumming School of Medicine University of Calgary

Induced pluripotent stem cells(iPSCs) were first generated by Yamanaka and colleagues over a decade ago. Since then, iPSCs have been successfully differentiated into many distinct cell types, enabling tissue-, disease-, and patientspecific in vitro modelling. Cardiovascular disease is the greatest cause of mortality worldwide but encompasses rarer disorders of conduction and myocardial function for which a cellular model of study is ideal. Although methods to differentiate iPSCs into beating cardiomyocytes(iPSC-CMs) have recently been adequately optimized and commercialized, the resulting cells remain largely immature with regards to their structure and function,demonstrating fetal gene expression, disorganized morphology, reliance on predominantly glycolytic metabolism and contractile characteristics that differ from those of adult cardiomyocytes. As such, disease modelling using iPSC-CMs may be inaccurate and of limited utility. However, this limitation is widely recognized, and numerous groups have made substantial progress in addressing this problem. This review highlights successful methods that have been developed for the maturation of human iPSC-CMs using small molecules,environmental manipulation and 3-dimensional(3 D) growth approaches.

关键词： Induced pluripotent stem cells Induced pluripotent stem cell-derived cardiomyocytes Regenerative medicine Stem cell biology Translational research

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Sensorimotor dysfunctions as primary features of autism spectrum disorders

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Science China(Life sciences) 2015年第10期58卷 1016-1023页

作者： Matthew W.MOSCONI John A.SWEENEY departments of Psychiatry and pediatrics University of Texas Southwestern Medical Center

Motor impairments in autism spectrum disorders(ASD) have received far less research attention than core social- communication and cognitive features. Yet, behavioral, neurophysiological, neuroimaging and histopathological studies have documented abnormal motor system development in the majority of individuals with ASD suggesting that these deficits may be primary to the disorder. There are several unique advantages to studying motor development in ASD. First, the neurophysiological substrates of motor skills have been well-characterized via animal and human lesion studies. Second, many of the single-gene disorders associated with ASD also are characterized by motor dysfunctions. Third, recent evidence suggests that the onset of motor dysfunctions may precede the emergence of social and communication deficits during the first year of life in ASD. Motor deficits documented in ASD indicate disruptions throughout the neuroaxis affecting cortex, striatum, the cerebellum and brainstem. Questions remain regarding the timing and development of motor system alterations in ASD, their association with defining clinical features, and their potential for parsing heterogeneity in ASD. Pursuing these questions through neurobiologically informed translational research holds great promise for identifying gene-brain pathways associated with ASD.

关键词： autism motor cerebellum dyspraxia oculomotor

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Adipose-brain crosstalk: do adipokines have a role in neuroprotection?

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Neural Regeneration Research 2015年第9期10卷 1381-1382页

作者： Jonathan P.Little Adeel Safdar School of Health and Exercise sciences University of British Columbia Okanagan departments of pediatrics and Medicine Mc Master University

Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline （Yates et al., 2012）. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role （Yates et al., 2012）. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite （Zhang et al., 1994） brings about the in- triguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology （Aguilar-Valles et al., 2015）. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communi- cate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk （Whitmer et al., 2005）, some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability （Tezapsidis et al., 2009; Wan et al., 2015）.

关键词： cell Adipose-brain crosstalk

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Yin and Yang of mesenchymal stem cells and aplastic anemia

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World Journal of Stem Cells 2017年第12期9卷 219-226页

作者： Larisa Broglie David Margolis Jeffrey A Medin Department of pediatrics Medical College of Wisconsin departments of pediatrics and Biochemistry Medical College of Wisconsin

Acquired aplastic anemia(AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells(HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells(MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis. Some of the observed clinical manifestations of AA can be explained by mesenchymal dysfunction. MSC infusions have been shown to be safe and may offer new approaches for the treatment of this disorder. Indeed, infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC destruction and help restore an environment that supports hematopoiesis. Small pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation have been attempted as treatments for AA. Here we review the current understanding of the pathogenesis of AA and the function of MSCs, and suggest that MSCs should be a target for further research and clinical trials in this disorder.

关键词： Hematopoiesis Targeted therapies Stem cells Hematopoietic stem cell transplantation Aplastic anemia Mesenchymal stem cells

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Pediatric nonalcoholic fatty liver disease:A clinical and laboratory challenge

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World Journal of Hepatology 2010年第7期2卷 275-288页

作者： Lucia Pacifico Eleonora Poggiogalle Vito Cantisani Guendalina Menichini Paolo Ricci Flavia Ferraro Claudio Chiesa departments of 1 pediatrics Sapienza University of Rome National Research Council Institute of Neurobiology and Molecular Medicine departments of Radiological sciences Sapienza University of Rome

The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determin ing the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nat ure of the study design. The natural history of pediat ric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk popul ation, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninv asive alternatives that will allow the prognosis of pediat ric NAFLD to be followed in large community or populat ionbased studies.

关键词： Nonalcoholic fatty liver disease Children Insulin resistance Ultrasound Magnetic resonance imaging

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Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children

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World Journal of Gastroenterology 2007年第12期13卷 1828-1832页

作者： MS El-Raziky M El-Hawary G Esmat AM Abouzied N El-Koofy N Mohsen S Mansour A Shaheen M Abdel Hamid H El-Karaksy departments of pediatrics Cairo University Cairo Egypt departments of Tropical Medicine Cairo University Cairo Egypt Tropical Medicine Research Institute Cairo Egypt

AIM: To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. METHODS: Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver ***: We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. CONCLUSION: Asymptomatic HCV infection is detectable in 2.02% Egyptian children.

关键词： Hepatitis C virus Child Egypt Prevalence Transfusion Risk factor

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Vascular dysfunction of postural tachycardia syndrome in children

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World Journal of pediatrics 2018年第1期14卷 13-17页

作者： Wei Bai Si-Yao Chen Hong-Fang Jin Jun-Bao Du Department of pediatrics Peking University First HospitalBeijing100034China Department of cardiac Surgery Guangdong CardiovascularInstituteGuangdong General Hospital and GuangdongAcademy of Medical SciencesGuangzhouChina

Background Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance, and its incidence in children is approximately 6.8% (1)The pathogenesis of POTS is complex with multiple, overlapping, interacting pathophysi-ological mechanisms. Although the specific pathogenic mechanism has remained perplexing, with the discovery of various gasotransmitters and biological peptides, the vascular dysfunction has aroused overwhelming attention. Data sources On the basis of searching in a wide range of recent original literatures, we reviewed the pathogenesis of vas-cular dysfunction in children with POTS. Results The flow-mediated vasodilation of POTS patients was greater than that of healthy controls, and the vasodilator factors were increased in patients with POTS under basal condition or under a standing position, while the vasoconstriction factors were reduced. Conclusions Vascular dysfunction, as one of pathogenesis in pediatric POTS patients, affects the occurrence and develop-ment of diseases through a variety of factors.

关键词： Children Postural orthostatic tachycardia syndrome Vasodilation

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The Variation in Plasma Cortisol Levels in Response to Anesthetic Induction with Etomidate or Ketamine in Children Undergoing Intracardiac Repair of Tetralogy of Fallot on Cardiopulmonary Bypass

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World Journal of Cardiovascular Surgery 2012年第2期2卷 17-20页

作者： Anil K. Pandey Sandeep Chauhan Neeti Makhija Usha Kiran Sumit Vasdev Sachin Talwar Ramakrishnan Lakshmy departments of cardiac Anaesthesia All India Institute of Medical Sciences New Delhi India departments of cardiac Biochemistry All India Institute of Medical Sciences New Delhi India departments of cardiac Surgery All India Institute of Medical Sciences New Delhi India

Objective: To compare the effect of a single induction dose of etomidate or ketamine on plasma cortisol levels in children with Tetralogy of Fallot (TOF) undergoing intra-cardiac repair on cardiopulmonary bypass (CPB). Design: A prospective randomized trial. Setting: cardiac center of a tertiary care hospital. Participants: Thirty children with TOF undergoing intra-cardiac repair on CPB. Interventions: After random allocation of the children into two groups, the children either received etomidate 0.2 mg/kg or ketamine 2 mg/kg intravenously for anesthetic induction along with fentanyl 2 mcg/kg and midazolam 100 mcg/kg. Endotracheal intubation was accomplished with rocuronium bromide in the dose of 1 mg/kg. Anesthesia was maintained with sevoflurane in air-oxygen, titrated to response and supplemental vecuronium bromide for muscle relaxation, fentanyl chloride for pain relief. Serum cortisol was measured on three occasions, at preinduction, at the end of surgery and at 24 hours postoperatively. Measurements and Main Results: Baseline plasma cortisol (Normal 5 - 25 mcg/dl) in the etomidate group (19.91 ± 3.51 mcg/dl) decreased significantly at the end of surgery (5.78 ± 2.0 mcg/dl) and rose to significantly higher than baseline values at 24 hours (27.31 ± 8.30 mcg/dl). The baseline cortisol levels in the ketamine group (20.91 ± 3.19 mcg/dl) increased significantly at the end of surgery (44.02 ± 5.49 mcg/dl) and remained significantly higher than baseline at 24hours (45.93 ± 3.05 mcg/dl). Plasma cortisol levels in the etomidate group at end of surgery, and at 24 hours post-operatively, were significantly lower than the ketamine group. Conclusions: This study shows that etomidate is a suitable and safe agent for suppression of the increase in serum cortisol associated with the use of CPB in children with TOF undergoing intra-cardiac repair.

关键词： Serum Cortisol Tetralogy of Fallot (TOF) Etomidate

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The Effects of Etomidate and Propofol Induction on Hemodynamic and Endocrine Response in Patients Undergoing Coronary Artery Bypass Graft Surgery on Cardiopulmonary Bypass

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World Journal of Cardiovascular Surgery 2012年第3期2卷 48-52页

作者： Anil K Pandey Neeti Makhija Sandeep Chauhan Sambhunath Das Usha Kiran A. K. Bisoi R Lakshmy departments of cardiac Anaesthesia All India Institute of Medical Sciences New Delhi India departments of cardiac Biochemistry All India Institute of Medical Sciences New Delhi India departments of cardiac Surgery All India Institute of Medical Sciences New Delhi India

Aim: To compare the effects of propofol and etomidate induction on hemodynamic parameters and serum cortisol levels in patients with normal left ventricular function undergoing elective coronary artery bypass graft surgery on cardiopulmonary bypass. Material and Method: After approval from the Institute Ethics committee hundred American Society of Anesthesiologists (ASA) grade II or III patients undergoing scheduled coronary artery bypass surgery on cardiopulmonary bypass were enrolled in the study. Patients were allocated randomly to receive either propofol or etomidate for anesthesia induction. Anesthesia was maintained in both groups with sevoflurane, vecuronium bromide for muscle relaxation (0.1 mg/kg, boluses) and fentanyl up to a total dose of 20 mcg/kg. Result: The baseline serum cortisol values were within normal limits in both the groups. The serum cortisol levels in the propofol group increased more than two fold, whereas the values in the etomidate group decreased by close to fifty percent on weaning from cardiopulmonary bypass (CPB). There was no significant difference in serum cortisol levels in the two groups at twenty-four hours after induction, although the values were close to double the baseline levels. Hemodynamically, etomidate group was more stable than propofol group following induction of anesthesia (P < 0.05). Conclusion: The surge in serum cortisol levels on the initiation of CPB seen after the use of propofol is prevented by the use of etomidate. Serum cortisol levels in both groups are well above the baseline at twenty-four hours without any untoward effects. Etomidate provides more stable hemodynamic parameters when used for induction of anesthesia as compared to propofol.

关键词： Etomidate Propofol Coronary Artery Bypass Grafting (CABG) Cardiopulmonary Bypass (CPB)

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Clinical observation of white eye distribution in patients with hyperlipidemia: an artificial intelligence digital visual examination technique

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Journal of Traditional Chinese Medicine 2025年

作者： SONG Tianli LI Haixia LIU Li'an Department of Cardiology， the Guang'anmen Hospital， China Academy of Chinese Medical sciences National College， Beijing University of Chinese Medicine

Objective: To explore the clinical observation of white eye distribution characteristics of hyperlipidemic patients based on artificial intelligence digital eye diagnosis technology. Methods: One hundred and fifty subjects were examined in the outpatient and inpatient departments of Guang'anmen Hospital of the China Academy of Traditional Chinese Medicine from 01 February 2022 to 01 February 2023， including 80 cases in the hyperlipidemic patient (HLP) group and 70 cases in the normal lipid level patient (NC) group. The two groups were collected and extracted by the artificial intelligence visual diagnostic instrument and analyzed by the MyEyeD-10 white eye shadowless imaging health intelligence analysis system. Finally， SPSS 26.0 (Version X; IBM Corp.， Armonk， NY， USA) was used for statistical processing. Results: Significant differences were noted in the scores of "spot" and "foggy" features between the two groups. Between groups， the "spot" feature score of the white eye morphology in the HLP group (11.07 ± 3.22) was higher than that in the NC group (7.50 ± 4.11) (P < 0.01). Moreover， the "foggy" feature score of the eye morphology in the HLP group (8.37 ± 2.25) was higher than that in the NC group (P < 0.01)， higher than that of the NC group (5.72 ± 1.21) (P < 0.05). There were significant differences in the "A" (stomach)， "B"， "O" (spleen)， and "M" (liver) eye-contact region scores between the two groups， and the "B"， "O" (spleen) and "M" (liver) eye-contact region scores were significantly different. The scores of the white eye channel region in the HLP group were significantly higher than those in the control group， with the "A"， "B"， and "O" regions (P < 0.01)， "M" region (P < 0.01)， "A"， "B"， "O"， and "M" region (P < 0.01). "M" zone (P < 0.05). The scores of "dull red" and "yellow" features were significantly different， and the scores of "dull red" and "yellow" colors of the white eye choroid in the HLP group were significantly higher than those in the HLP g

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