Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells.

Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.

MicroRNA-22-3p alleviates atherosclerosis by mediating macrophage M2 polarization as well as inhibiting NLRP3 activation.

OBJECTIVE: MicroRNA (miR)-22-3p is expressed in atherosclerosis (AS), but its function and regulatory mechanisms remain unclear. Therefore, the effects of miR-22-3p in AS were assessed in this study. METHODS: MiR-22-3p expression was assessed in AS, and miR-22-3p target genes were predicted using sequencing transcriptomics. The effect of miR-22-3p agomir on atherosclerotic lesions in an AS mouse model were determined by Oil red O, Masson's, and sirius red staining, and by anti-smooth muscle actin and macrophage antigen-3 immunostaining. Gene expression in AS was evaluated by western blot and immunofluorescence. RESULTS: MiR-22-3p was expressed in AS and control samples (32.5% and 33.9% levels, respectively, relative to total miRNA among six highly expressed miRNAs). In the mouse model of AS, miR-22-3p agomir significantly reduced lipid deposition, proliferation of aortic collagen fibres, and macrophage content. Additionally, inducible nitric oxide synthase, interleukin-6, and tumour necrosis factor-α levels were significantly reduced, and levels of arginase 1 and CD206 were significantly enhanced. MiR-22-3p was found to target janus kinase 1(JAK1), and significantly inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) and JAK1 in mice. CONCLUSIONS: MiR-22-3p appears to reduce the inflammatory response in AS, which might be achieved by inducing the M2 macrophage phenotype and suppressing NLRP3 activation via JAK1.

Correlation study on the relationship between dyslipidemia and carotid intima-media thickness in patients with diabetes mellitus.

Objective: To investigate the correlation between dyslipidemia and carotid intima-media thickness (IMT) in patients with diabetes mellitus. Methods: A descriptive research design was adopted in this study. One hundred and twenty patients with Type-2 diabetes mellitus who were admitted to the physical examination center of The Fourth Hospital of Hebei Medical University from June 2020 to June 2021 for physical examination were recruited to the experimental group. The 120 patients were divided into three groups according to carotid IMT: normal group, thickened group, and plaque group. Forty healthy people who underwent a physical examination during the same period were recruited as the control group. The differences in IMT in various parts of the experimental group and the control group and the differences in blood lipid indexes were compared and analyzed. In addition, the correlation between mean IMT of bilateral common carotid arteries and blood lipid levels in normal, thickened and plaque groups was compared and analyzed. Results: The intima-media thicknesses of the internal carotid artery and bilateral common carotid arteries of the patients in the experimental group were significantly thicker than those in the healthy control group, the levels of TC, TG and LDL were higher than those in the control group, while the level of HDL was lower than that in the control group, with a statistically significant difference (p=0.00). The levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and LDL were positively correlated with the mean IMT of bilateral common carotid arteries (p<0.05), while the level of HDL was negatively correlated with the mean IMT of bilateral common carotid arteries (p<0.05). Conclusion: Dyslipidemia and glucose metabolism in patients with Type-2 diabetes mellitus have a close bearing on carotid IMT. Clinically, patients with Type-2 diabetes mellitus can be judged by monitoring carotid IMT for dyslipidemia, atherosclerosis and other related complications.

Utilization of pillar[5]arene-based ICT probes embedded into proteins for live-cell imaging and traceable drug delivery.

Three protein microenvironment-sensitive pillar[5]arene-based fluorescent probes (3/4/5C-B) were designed and synthesized based on intramolecular charge transfer (ICT) mechanism. Unlike the majority of micromolecular ICT probes, the aforementioned probes displayed differentiated sensitivity to multiple proteins. The 7-(diethylamino)coumarin-3-formic acid (DCCA) group in the probes was essential for their sensitivity. The presence of a pillar[5]arene group was also crucial as they benefit 3/4/5C-B form complexes with the proteins, although it changed the electron density distribution of the DCCA group. 3/4/5C-B exhibited favorable carrier ability for regorafenib (REG). 4C-B had the best spatial structure for complexation. The 3/4/5C-B-REG complexes would assemble into high drug-loading fluorescent nanoparticles in a physiological environment (pH = 7.4). Such nanoparticles exhibited pH-triggered enrichment ability, which rapidly enriched REG in the acidic environment (pH = 6.0). Moreover, the complexation between 3/4/5C-B and REG maintained the live-cell membrane imaging property of the probes and the excellent targeted anticancer activity of the drug.

Molecular Mechanisms of Iron Mediated Programmed Cell Death and Its Roles in Eye Diseases.

Ferroptosis, a newly identified, iron-dependent type of programmed cell death, is active in several diseases, such as heart disease, brain damage, and cancer. Its main characteristics commonly involve excess iron accumulation, elevated lipid peroxides and reactive oxygen species, and reduced levels of glutathione and glutathione peroxidase 4 levels. The effects of ferroptosis in eye diseases cannot be underestimated, with ferroptosis becoming a research target in ocular disorders and emerging evidence from a series of in vivo and in vitro researches into ferroptosis revealing its role in eye conditions. However, no report provides comprehensive information on the pathophysiology of ferroptosis in eye diseases and its possible treatments. In the current review, we present an up-to-date overview of ferroptosis biology and its involvement in the pathological processes of ocular diseases. Furthermore, we pose several outstanding questions and areas for future research in this topic. We deem ferroptosis-associated cell death a pivotal new field of scientific study in ocular diseases and consider it a new therapeutic target in the treatment of some eye disorders.

Strehl Ratio and Myopia in Chinese Adolescents: The Tuyou County Pediatric Eye (TYPE) Study.

AIM: To investigate the relationships between property of the visual quality, Strehl ratio (SR) and the degree of myopia. METHODS: A total of 444 anatomically normal eyes of 222 adolescents were enrolled in the TYPE study. Based on spherical equivalent (SE), subjects were divided into four groups: emmetropia/control (SE: +0.75 to -0.75 D), low myopia (SE: -0.75 to -3.00D), moderate myopia (SE: -3.00 to -5.00D), high myopia (SE: <-5.00D). Axial length (AL) was measured. SR was attained with an OPD-III SCAN and calculated under a 3 mm pupil diameter. RESULTS: The overall SR (mean ± SD) was 0.40 ± 0.08. Among all included eyes, the SR in eyes with the emmetropia, low myopia, moderate myopia and high myopia was 0.80 ± 0.11, 0.31 ± 0.04, 0.21 ± 0.11, and 0.11 ± 0.02, respectively. Furthermore, the K2 in eyes with the emmetropia, low myopia, moderate myopia and high myopia was 43.83±1.50, 43.96±1.37, 43.4±5.52, and 45.16±1.43, respectively. Significant differences were detected within the four groups in terms of SR and K2 (P < 0.001). Multiple regression analysis confirmed that AL negatively affected SR independently (P < 0.001). CONCLUSION: Our findings provide a useful basis for the conclusion that myopia affects visual quality SR in Chinese adolescents. Besides, when performing visual quality SR, axial length must be taken into consideration, as it will influence SR.

TuYou-County Pediatric Eye (TYPE) study, design issues, baseline demographic characteristics, and implications: Report number 1.

ABSTRACT: To report the rationale, design, and baseline demographic characteristics of TuYou-County Pediatric Eye study, which mainly aimed to determine the retinal microvascular changes with optical coherence tomography angiography (OCTA) and its association with eye abnormalities in school aged children and adolescents at suburban location in Northern China.TuYou-County Pediatric Eye study was a school-based survey conducted in TuYou-County. Multi-ethnic (Mongol, Han, and Hui) participants will be followed up for 5 years. Standardized ophthalmological examinations include visual acuity, ocular biometry, retinal photography, and OCTA. A questionnaire survey was conducted to collect variables regarding to eye disease such as parental history of eye diseases, near work, outdoor activities, living and eating habits, etc.After sampling, 687 participants were eligible for investigation, and 20 students did not attend the investigation, living 667 (response rate, 97.1%) students completed questionnaires and all ocular examinations. The average age of all participants was 14.9 ±â€Š5.11.TYPE study is the first large-scale school-based multi-ethnic survey in suburban site of Northern China. Continuous identification of retinal microvascular changes with eye diseases will provide new insights into the control related diseases in school-age children and adolescents.

Quantitative Analysis of the Macular and Peripapillary Capillary Network with Optical Coherence Tomography Angiography in Chinese Adolescents: The Tuyou County Pediatric Eye (TYPE) Study.

AIM: To use OCTA to collect normative data describing the vascular perfusion of the macula and optic disc in adolescents. METHODS: This cross-sectional, school-based study was conducted from Oct 15, 2019, to Nov 30, 2019, in Tuyou County, Baotou, China. All eligible participants underwent a comprehensive questionnaire and ocular examination. The vascular perfusion of the macula and optic disc was determined using a spectral-domain OCTA device. RESULTS: A total of 570 anatomically normal eyes without a history of pathologic disease from 570 adolescents (mean ± SD age, 15.1 ± 1.9 years; 298 girls [52.3%]) were enrolled. In the macula, the mean ± SD perifoveal perfusion density (PD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was 44.2% ± 4.37% and 50.74% ± 3.98%, respectively. The mean ± SD foveal avascular zone (FAZ) was 0.32 mm2 ± 0.11 mm2. The mean ± SD peripapillary vessel density (PVD) was 54.98% ± 3.53%. The inferior hemiretinal SCP-PD, DCP-PD, FAZ, and PVD was larger in girls than boys (P = 0.006, P = 0.001, P < 0.001, and P = 0.006, respectively) Multiple regression analysis confirmed that sex independently affected the DCP-PD, FAZ, and PVD (P < 0.001, P < 0.001, and P = 0.029, respectively) and that axial length (AL) independently affected the FAZ area and PVD (P = 0.004 and P < 0.001, respectively). CONCLUSION: Quantitative studies of the perifoveal vasculature in adolescents should consider the patient's sex and AL. Our findings may provide useful information for the understanding and the management of retinal perfusion in Chinese adolescents.

Global, national and regional prevalence, and associated factors of ocular trauma: A protocol for systematic review and meta-analysis.

BACKGROUND: Ocular trauma is a common eye disease and one of the main causes of blindness. There is a dearth of data on a summary and meta-analysis on the global epidemiology of the disease. Therefore, this systematic review protocol aims to propose the first systematic review and meta-analysis to synthesize existing evidence on the global prevalence and associated factors of ocular trauma worldwide. METHODS: A systematic search will be performed according to the following databases: PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Weipu, and Wanfang. Cross-sectional, case-control, and cohort studies reporting on the prevalence and risk factors of ocular trauma will be included. The primary outcome will be the prevalence in global, regional, and national ocular trauma. Study searching, data extraction, and quality evaluation will be performed by 2 reviewers, independently. Appropriate meta-analysis will then be used to pool studies. STATA software package v 12.0 (Stata Corporation, College Station, TX) and R (version 3.4.1; R Foundation for Statistical Computing, Vienna, Austria) software will be used for all statistical analyses. RESULTS: This study will provide a high-quality synthesis to examine the prevalence and associated factors of ocular trauma worldwide. Furthermore, current study will project disease estimates in the next 50 years. CONCLUSION: This systematic review and meta-analysis will provide first evidence to evaluate the burden of ocular trauma in the general population. ETHICS AND DISSEMINATION: This systematic review and meta-analysis of randomized controlled trials does not require ethical recognition, and the results of this paper will be published in an open access, internationally influential academic journal. TRIAL REGISTRATION NUMBER: CRD42020189166.

Adapting and validating a developmental assessment for chinese infants and toddlers: The ages & stages questionnaires: Inventory.

The Chinese government has announced the 2013 Guidelines for developing a national system for early detection of disability among children under 6 years of age. However, given limited resources, challenges exist with developmental measures required in the 2013 Guidelines. In order to meet the needs for a more accurate and cost-efficient measure for developmental assessment, the Ages & Stages Questionnaires: Inventory (ASQ:I) was translated into Simplified Chinese, and validated on a regional sample of 812 Chinese children ages from 1 to 25 months. Results indicated that the Chinese ASQ:I domain scores increased across children's age. When dividing the sample into seven age intervals, Cronbach's alpha in each interval ranged from 0.59 to 0.96 across five domains. When using the whole sample for analyses, item expected a posteriori/plausible value (EAP/PV) reliability was above 0.99 in all domains, test-retest reliability using intra-class correlation analyses ranged from 0.95 to 0.99, and the agreement with the concurrent measure ranged from 0.29 to 0.89. Domain scores on the ASQ:I correctly predicted 92-99% of participating children's disability status. Findings suggested that the Chinese ASQ:I has adequate psychometric properties and thus provides a promising alternative measure for screening and progress monitoring in young children in China. Implications for future research and implementation are discussed.

ADAPTING A PARENT-COMPLETED, SOCIOEMOTIONAL QUESTIONNAIRE IN CHINA: THE AGES & STAGES QUESTIONNAIRES: SOCIAL-EMOTIONAL.

The Ages & Stages Questionnaire: Social-Emotional (ASQ:SE; Squires, Bricker, & Twombly, 2002a), developed in the United States, was translated and adapted for use in China. Lack of valid and reliable instruments for identifying social and emotional delays in young children is a worldwide issue. Professionals in China have recently focused efforts on developing methods for early identification of social, emotional, and behavioral issues in the birth-to-5 population. Following the guidelines of the International Test Commission, the ASQ:SE was translated into Simplified Chinese (ASQ:SE-C) to collect a normative sample of 2,528 children across China. Data were analyzed to evaluate the psychometric properties of the ASQ:SE-C, using both classical test theory and item response theory, including generating cutoff points appropriate for the Chinese sample. A panel of Chinese experts was surveyed to assess face validity and estimated utility of the newly adapted tool. Discussions of research findings and implications for future studies are provided.

The Effect of Air Pollution on the Occurrence of Nonspecific Conjunctivitis.

Purpose. To investigate the short-term effect of air pollution on occurrence of nonspecific conjunctivitis. Methods. Data were collected from outpatient visits from cases with conjunctivitis over a period of one year. Regression analysis was performed to evaluate the relationship between the number of outpatient visits and the air quality and the lag effect of air quality on conjunctivitis occurrence. Results. The air quality index on the day of presentation (P = 0.023), one day before presentation (P = 0.049), and two days before presentation day (P = 0.050) had a positive relation with outpatient visits for conjunctivitis. The air quality index (P = 0.001) and outpatient visits number per day (P = 0.013) in autumn and winter (October to March) were significantly higher than those in spring (April) and summer (September). Conclusions. The air quality index within two days before presentation affected the probability of attending the outpatient clinic for nonspecific conjunctivitis. High number of cases can be expected in colder season.

Relationship Between Iodine Concentration in Maternal Colostrum and Neurobehavioral Development of Infants in Shanghai, China.

It is well known that iodine plays an important role in the process of early growth and development of most organs, especially the brain. However, iodine concentration in the colostrum and its association with the neurobehavioral development of infants remains unclear. Colostrums from 150 women were collected, and their iodine concentrations were measured. The median colostrum iodine level was 187.8 µg/L. The Bayley Scales of Infant and Toddler Development-III test was performed when the infants were about 18 months. The mean cognitive, language, and motor composite scores were 105.3 ± 9.8, 105.2 ± 11.1, and 104.6 ± 6.7, respectively. And the mean scores of the 5 subtests were 11.1 ± 2.0, 9.3 ± 2.0, 12.4 ± 2.3, 11.1 ± 1.2, and 10.4 ± 1.2, respectively. No statistically significant difference was observed in the cognition, language, or motor development of infants across different levels of colostrum iodine. After adjusting for a range of confounding factors, colostrum iodine concentration was a predictor of motor development, specifically gross motor development.

[Studies of the norm and psychometrical properties of the ages and stages questionnaires, third edition, with a Chinese national sample].

OBJECTIVE: To introduce the Ages and Stages Questionnaires, Third Edition (ASQ-3), to China, created ASQ-Chinese (ASQ-C) and carried out studies of its national norm and the psychometrical properties in the children aged 1-66 months in the mainland of China in collaboration with the author of the ASQ System and under the authorizations from its publisher on translation, researches, publication and distribution of the ASQ-3. METHOD: The ASQ-3 questionnaires were translated and adapted into a Simplified Chinese version, the ASQ-C, with six steps such as translation, back-translation and adaptation and so on to ensure consistency with the core of the original document and to have the cultural relevance in China.A stratified cluster sampling method was utilized to recruit children aged 1-66 months with respect to demographic characteristics such as the proportion of population in each administrative region and in urban and rural areas and so on that are representative of 2010 China census data.A sample size of over 200 was collected for each ASQ-C age interval.Children were excluded from the normative sample who (1) are from communities or villages at an elevation of 2 000 m or above and(or) where simplified Chinese is not the official language, or (2) had been diagnosed as having a developmental delay by any authoritative organizations.The national normative sample for the ASQ-C had a total sample size of 4 452, sample size within each age interval ranged from 218 to 227, including 2 230 male cases and 2 222 female cases, 2 236 urban cases and 2 216 rural cases.A convenience sample was recruited from the normative sample to examine inter-rater reliability and test-retest reliability in all six administrative regions.Researchers completed the ASQ-C on the same child with their parents for 162 children for inter-rater reliability(the size of each ASQ-C age interval was 5-9); parents of 168 children completed another age-appropriate ASQ-C for test-retest reliability during 10-15 days after they completed the normative ASQ-C(The size of each ASQ-C age interval is 6-10). Another convenience sample was recruited from the follow-up of low birth weight infants for the concurrent validity of the ASQ-C in comparison with the Beijing Gesell.Parents of 198 children completed age-appropriate ASQ-C and professional administered to the children with the Beijing Gesell.In the ASQ-C norm and test-retest reliability, parents completed the age-appropriate ASQ-C, independently or with needed assistance. In inter-rater reliability, researchers completed the same ASQ-C after parents. In validity test, after parents completing age-appropriate ASQ-C, professional tested children with the Beijing Gesell.Data were analyzed using SPSS version 13.0 software.The mean and standard deviation of the national normative sample were calculated, reliability and validity of the ASQ-C was examined. RESULT: The demographic characteristics of this Chinese sample match the 2010 China census data on gender, urban or rural location, and family income.All 20 intervals of the ASQ-C were standardized on 21 national normative samples.Cronbach's alpha coefficient for the whole measure was 0.8.The Pearson correlation coefficient between the ASQ-C total scores of the two raters was 0.8.The Pearson correlation coefficient between the ASQ-C total scores of the two times was 0.8 (all P<0.000 1). The sensitivity of ASQ-C was 87.50% and the specificity of ASQ-C was 84.48%.The percentage of the agreement between the ASQ-C and the Beijing Gesell was 84.74%. CONCLUSION: These findings indicate that the ASQ-C is a reliable and valid measure with a representative national sample aged 1-66 months.It can be used to screen and monitor the development of children in the mainland of China.

[Studies of the norm and psychometric properties of Ages and Stages Questionnaires in Shanghai children].

OBJECTIVE: To introduce the Ages and Stages Questionnaire (ASQ) to China, we created ASQ-Chinese (ASQ-C) and carried out studies of its norm and the psychometrical properties in Shanghai children aged 3-66 months in collaboration with the author of the ASQ with the permissions from the publisher. METHOD: The 19 ASQ intervals were translated into Chinese, to make the ASQ-C culturally relevant, and back translated into English. The project used a stratified cluster sampling method and recruited children aged 3 - 66 months with respect to demographic characteristics that were representative of Shanghai census data, and excluded the children whose mother tongue was not Chinese and/or diagnosed with disabilities by the authoritative hospitals in Shanghai. Parents/caregivers of the 8472 children either independently completed the age-appropriate ASQ-Cs or completed with help from the researchers for the normative samples. Among them, professionals completed the age-appropriate ASQ-C again for 519 children within six days after the parents/caregivers completed the ASQ-C for inter-rater reliability. In terms of test-retest reliability, 651 parents completed another age-appropriate questionnaires within a 10- to 23-day interval. For concurrent validity, BSIDII were administered with 255 children from 6, 12, 18, 24, and 30-month ASQ-C age intervals. The cutoffs of the ASQ-C and the BSIDII were all set at the two standard deviations below the means. The statistical analysis was carried out using SPSS 13.0. RESULT: The ASQ-Cs were independently completed by 85.25% of the parents/caregivers; the percentage of gender, family income and region of residence were similar to the Shanghai population census conducted in the recent years. Two standard deviations below the means were used as the cutoff scores of the ASQ-Cs across the age intervals. In terms of internal consistency of the ASQ-C, Cronbach standardized alpha was 0.77. The Pearson correlation coefficient between the ASQ-C total scores of the two testers was 0.84 (P < 0.0001). The Pearson correlation coefficient between the ASQ-C total scores of the two tests was 0.82 (P < 0.0001). The percentage of the agreement between the ASQ-C and the BSID II was 84.31%, the sensitivity of ASQ-C was 85.00%, and the specificity of ASQ-C was 84.26%. CONCLUSION: It is practicable that the ASQ-C can be completed by the parents/caregivers of Shanghai children. ASQ-C has solid psychometric properties and is worthy of further research and introduction to China.

[Cutoff scores of the Ages and Stages Questionnaire-Chinese for screening infants and toddlers].

OBJECTIVE: To study the validity and accuracy of differing cutoff scores of the Ages and Stages Questionnaires-Chinese (ASQ-C) for screening infants and toddlers in comparison with the gold standard, Bayley Scale of Infant Development, Second Edition (BSID II). METHOD: The 269 samples were enrolled from the normative children, aged 3 - 31 months, of the ASQ-C in Shanghai. The age-appropriate ASQ-Cs were completed by parents/caregivers and the BSIDIIwas administered by professionals. The cutoff scores of -2 standard deviation (s), -1.5 s, and -s for the ASQ-C were examined against BSID II with the cutoff scores set at -2 s as the standard of developmental delay, -s as the standard of suspected developmental delay and developmental delay respectively. Agreement between the classifications of the ASQ-C (i.e., typical, suspected, delay) was compared with the classification of the BSID II (typical, suspected, delay), sensitivity, specificity, Youden Index and area under ROC curve of ASQ-C were examined. The statistical analysis was carried out using SPSS 13.0. RESULT: When the cutoff score for BSID II was -2 s, the -2 s cutoff score for ASQ-C exhibited the following properties: the highest agreement of 83.64%, the sensitivity and specificity both above 80% being respectively 88.46% and 83.13%, the highest Youden Index of 0.72 and the largest area of 0.86 under ROC curve. The -1.5 s cutoff score for ASQ-C showed the following properties: 71.75% agreement, 100% sensitivity, 68.72% specificity, Youden Index = 0.69, the area under ROC curve = 0.84. The -s cutoff score for ASQ-C showed the following properties: the lowest agreement of 55.02%, 100% sensitivity, the lowest specificity of 50.21%, the lowest Youden Index of 0.50, and the smallest area of 0.75 under ROC curve. When the cutoff score for BSID II was set at -s, the -2 s for ASQ-C showed the following properties: the highest agreement of 85.87%, the lowest sensitivity of 68.57%, the highest specificity of 91.96%, Youden Index = 0.61, the smallest area = 0.77 under ROC curve. The -1.5 s for ASQ-C showed the following properties: the agreement of 80.67%, the sensitivity and specificity both above 70% being respectively 85.71% and 78.89%, the highest Youden Index of 0.65, the largest area of 0.82 under ROC. The -s cutoff score for ASQ-C showed the following properties: the lowest agreement of 68.40%, the highest sensitivity of 94.29%, the lowest specificity of 59.30%, the lowest Youden Index of 0.54, and the area under ROC curve = 0.80. When the cutoff score for BSID II was -1 to 2 s, the identifying percentages of the -2 s, -1.5 s and -s for the ASQ-C were 56.82%, 77.27% and 90.91%, respectively. CONCLUSION: For developmental delay identification, the -2 s cutoff score for ASQ-C produces the most robust validity and highest accuracy; for the identification of suspected developmental delay and developmental delay, the -1.5 s cutoff score for ASQ-C has the highest screening accuracy with appropriate sensitivity and specificity; for identifying the suspected developmental delay, the -s cutoff score for ASQ-C has the highest percentage of the identification. It is necessary to add 1 - 2 s to the ASQ-C's cutoff scores as the standard for screening suspected developmental delays.

[Establishing the norm of cognitive adaptive test/clinical linguistic and auditory milestone scale in the children from 4 to 36 months of age in Shanghai, China].

OBJECTIVE: To meet the need for instrument assessing the cognitive abilities of infants and young children as well as discriminating between global developmental delay and particular deficits in either language or problem-solving skills, we intended to introduce Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) into China. METHODS: CAT/CLAMS were administered to 1604 normative children aged 4-36 months (in 16 age groups, about 100 children per age group) in Shanghai during the period from December 2003 to June 2004. In the meantime, Gesell Developmental Diagnosis was applied for 100 of these children, respectively aged 4, 6, 12, 18 and 30 months (20 children per age group). Interclass correlation coefficients (ICC) were adopted to analyze data in terms of inter-rater reliability and re-test reliability of the scales of CAT/CLAMS. Cronbach alpha coefficients were calculated to assess the inter consistency of the scales. Pearson correlation coefficients(r) were adopted to analyze the concurrent validity of the scales. The normative percentile graphs of CAT/CLAMS in the children from 4 to 36 Months of age in Shanghai, China were adopted. RESULTS: Administrations of the CAT/CLAMS for each subject usually took 10-20 minutes. Individual scores (CLAMS, CAT, and CAT/CLAMS) increased with ages (Pearson correlation coefficients were 0.96, 0.98 and 0.98, respectively, P < 0.01 for all). ICCs (intraclass correlation coefficient) in terms of individual scores for the inter-rater reliability test and the re-test reliability test were respectively > or = 0.96 (P < 0.01) and > or = 0.95 (P < 0.01), all the Cronbach alpha coefficients were > or = 0.98; in 100 children of the 5 age groups, there was significantly positive correlation between CAT/CLAMS and Gesell Developmental Diagnosis in terms of language skill DQ and adaptive skill DQ, and Full Scale DQ (r = 0.517, 0.703, 0.613, respectively, P < 0.01 for all). Moreover, this significant positive correlation was observed in each of the 5 age groups (r = 0.455-0.827, P < 0.05). CONCLUSION: CAT/CLAMS is suitable for discriminating between global developmental delay and particular deficits in either language or problem-solving skills. It is a quick, reliable, and valid instrument, with refined and quantified results. It is a good tool for developmental surveillance and screening of infants and young children.