Reconstructing in vivo spatially offset Raman spectroscopy of human skin tissue using a GPU-accelerated Monte Carlo platform

As one type of spatially offset Raman spectroscopy(SORS), inverse SORS is particularly suited to in vivo biomedical measurements due to its ring-shaped illumination scheme. To explain inhomogeneous Raman scattering during in vivo inverse SORS measurements, the light–tissue interactions when excitation and regenerated Raman photons propagate in skin tissue were studied using Monte Carlo simulation. An eight-layered skin model was first built based on the latest transmission parameters. Then, an open-source platform, Monte Carlo e Xtreme(MCX), was adapted to study the distribution of 785 nm excitation photons inside the model with an inverse spatially shifted annular beam. The excitation photons were converted to emission photons by an inverse distribution method based on excitation flux with spatial offsets Δs of 1 mm, 2 mm, 3 mm and 5 mm. The intrinsic Raman spectra from separated skin layers were measured by continuous linear scanning to improve the simulation accuracy. The obtained results explain why the spectral detection depth gradually increases with increasing spatial offset, and address how the intrinsic Raman spectrum from deep skin layers is distorted by the reabsorption and scattering of the superficial tissue constituents. Meanwhile, it is demonstrated that the spectral contribution from subcutaneous fat will be improved when the offset increases to 5 mm, and the highest detection efficiency for dermal layer spectral detection could be achieved when Δs = 2 mm. Reasonably good matching between the calculated spectrum and the measured in vivo inverse SORS was achieved, thus demonstrating great utility of our modeling method and an approach to help understand the clinical measurements.

Involvement of PPARs in the regulation of brain CYP2D by growth hormone

OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue-specificity.The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone.METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum.The animals were tested with rotarod apparatus,balance beam,water maze,elevated plus maze and open field.The changes in CYP2D22,PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice,SH-SY5 Y cells and HepG2 cells.RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice.Compared with WT mice,CYP2D expression was lower in brain regions from GHR(-/-)male mice;however,hepatic CYP2D level was similar.Pulsatile GH decreased PPARα m RNA level,and increased m RNA levels of CYP2D6 and PPARα in SH-SY5 Y cells.In HepG2 cells,pulsatile GH resulted in decreases in PPARα and PPARγ m RNA levels,but not CYP2D6.PPARα inhibitor induced CYP2D6 m RNA and protein by 1.32-fold and 1.43-fold in SH-SY5 Y cells.PPARγ inhibitor decreased CYP2D6 m RNA and protein by 74.76% and 40.93%.PPARα agonist decreased the level of CYP2D22 m RNA in liver and cerebellum,while PPARγ agonist rosiglitazone resulted in diametrically increases.The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function.Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%,promoted the binding of PPARγ with CYP2D6 promoter by approximate60%.The levels of brain and liver PPARα expression in male GHR(-/-)mice is obviously higher than those in WT mice.The level of PPARγ in male GHR(-/-)mice was decreased in the frontal cortex and hippocampus,while remained stable in the cerebellum and striatum;meanwhile,PPARγ was increased in the liver.CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system.Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter,leading to the elevated brain CYP2D in a tissue-specific manner.Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system(such as serotonin) through the specific regulation of brain CYP2D expression.

Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study

Background An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan,Hubei,China.People of all ages are susceptible to SARS-CoV-2 infection.No information on severe pediatric patients with COVID-19 has been reported.We aimed to describe the clinical features of severe pediatric patients with COVID-19.Methods We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU),Wuhan Children's Hospital from January 24 to February 24.We collected information including demographic data,symptoms,imaging data,laboratory findings,treatments and clinical outcomes of the patients with severe COVID-19.Results The onset age of the eight patients ranged from 2 months to 15 years;six were boys.The most common symptoms were polypnea (8/8),followed by fever (6/8) and cough (6/8).Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six.Laboratory findings revealed normal or increased whole blood counts (7/8),increased C-reactive protein,procalcitonin and lactate dehydrogenase (6/8),and abnormal liver function (4/8).Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8),increased CD3 (2/8),CD4 (4/8) and CD8 (1/8),IL-6 (2/8),IL-10 (5/8) and IFN-γ (2/8).Treatment modalities were focused on symptomatic and respiratory support.Two critically ill patients underwent invasive mechanical ventilation.Up to February 24,2020,three patients remained under treatment in ICU,the other five recovered and were discharged home.Conclusions In this series of severe pediatric patients in Wuhan,polypnea was the most common symptom,followed by fever and cough.Common imaging changes included multiple patch-like shadows and ground-glass opacity;and a cytokine storm was found in these patients,which appeared more serious in critically ill patients.

SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China

Background The clinical characteristics and outcome of COVID-19 in children are different from those in adults.We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19.Methods We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children's Hospital from January 26 to March 22,2020.Clinical features,chest imaging findings,laboratory tests results,treatments and clinical outcomes were analyzed.Results The mean age of the infected infants was 6.43 months,with a range of 2-12 months.61.11% of the patients were males and 38.89% females.86.11% of the infants were infected due to family clustering.Cough (77.78%) and fever (47.22%) were the most common clinical manifestations.Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia.47.22% of the infants developed complications.Increased leucocytes,neutrophils,lymphocytes,and thrombocytes were observed in 11.11,8.33,36.11 and 44.44% of infants,respectively.Decreased leucocytes,neutrophils,thrombocyte and hemoglobin were observed in 8.33,19.44,2.78 and 36.11% of infants,respectively.Increased C-reactive protein,procalcitonin,lactate dehydrogenase,alanine aminotransferase,creatine kinase and D-dimer were observed in 19.44,67.74,47.22,19.44,22.22 and 20.69% of infants,respectively.Only one infant had a high level of creatinine.Co-infections with other respiratory pathogens were observed in 62.86% of infants.CD3 (20.69%),CD4 (68.97%),CD19 (31.03%) and Th/Ts (44.83%) were elevated;CD8 (6.9%) and CD16+CD56 (48.28%) was reduced.IL-4 (7.69%),IL-6 (19.23%),IL-10 (50%),TNF-α (11.54%) and IFN-γ (19.23%) were elevated.Up to March 22,97.22% of infants recovered,while a critical ill infant died.When the infant's condition deteriorates rapidly,lymphocytopenia was discovered.Meanwhile,C-reactive protein,D-dimer,alanine aminotransferase,creatine kinase,creatinine,IL-6 and IL-10 increased significantly.Conclusions In the cohort,we discovered that lymphocytosis,elevated CD4 and IL-10,and co-infections were common in infants with COVID-19,which were different from adults with COVID-19.Most infants with COVID-19 have mild clinical symptoms and good prognosis.