Health-related quality of life of children with Williams syndrome and caregivers in China.

Introduction: Williams syndrome (WS) is a rare genetic disorder that impacts multiple systems and may cause developmental delays. These medical and developmental issues impose a heavy burden on affected children and their families. However, there was no study on children's health-related quality of life (HRQoL) with WS and only two studies about family quality of life globally. Therefore, the primary purpose of this study was to assess the HRQoL of children with WS and their caregivers in China, and the secondary purpose was to identify the potential determinants of children's and caregivers' HRQoL. Methods: In total, 101 children and caregivers were included. We applied the proxy-reported PedsQL 4.0 Generic Core Module (PedsQL GCM) and PedsQL 3.0 Family Impact Module (FIM) to measure the HRQoL of children and caregivers. Additionally, we collected information on a comprehensive set of social demographic and clinical characteristics. Differences in HRQoL scores across subgroups were assessed by two-independent-samples t-tests, one-way ANOVA, and post hoc tests. We also calculated effect sizes to indicate clinical relevance. Multivariate linear regression models were applied to assess the potential determinants of HRQoL. Results: We found that the HRQoL of children with WS and their caregivers was dramatically worse than the norm average scores of the healthy controls of children published in previous studies. Paternal educational level, household income, and the perceived financial burden significantly influenced the HRQoL of both children and families (p-values < 0.05). Multivariate linear regression analysis showed that the perceived financial burden was independently associated with family quality of life (p-values < 0.05)., and the presence of sleeping problem was independently associated with children's HRQoL (p-value = 0.01). Conclusion: We call for attention from policymakers and other stakeholders on the health status and well-being of children with WS and their families. Supports are needed to relieve psychosocial distress and financial burden.

The Inhibition of Adipose-Derived Stem Cells on the Invasion of Keloid Fibroblasts.

Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, the molecular mechanisms have not been fully elucidated. Objectives: to explicitly demonstrate the relationship between adipose-derived stem cells alleviating keloids and alterations of Col-1, Col-3, CTGF, and P-4-HB. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into two groups, one co-cultured with adipose-derived stem cells and the other grown independently. We compared the wound-healing rates, fibroblast survival rates, apoptosis rates, mRNA expressions, and protein levels of Col-1, Col-3, CTGF, and P-4-HB between separated groups. Results: We found no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate at the baseline. With adipose-derived stem cells, wound-healing rate and survival rate of normal fibroblasts were promoted, whereas in keloid fibroblasts, they were reduced. The apoptosis rate of normal fibroblasts and keloid fibroblasts were restrained, with the restraint in keloid fibroblasts being more evident. The protein levels of Col-3, CTGF, and P-4-HB were lower in keloid fibroblasts co-cultured with adipose-derived stem cells than in normal fibroblasts under similar conditions. Conclusions: Adipose-derived stem cells strongly suppressed keloid fibroblasts' proliferative and invasive behavior. However, adipose-derived stem cells negatively regulated keloid fibroblast apoptosis. Adipose-derived stem cells can be a potential keloid therapy worth further investigation.

[Early motor development in children with Williams syndrome]. / Williams综合征儿童早期运动发育特征.

OBJECTIVES: To study the early motor development of children with William syndrome (WS). METHODS: The medical data of 59 children with WS (40 males and 19 females) aged 0-24 months from September 2018 to August 2021 were retrospectively analyzed. Based on the test results of the Peabody Developmental Motor Scale II, the motor development ability of the children of different ages was analyzed. RESULTS: There was no significant difference in age and motor quotient between boys and girls (P>0.05). For the age groups of <6 months, 6 to <12 months, 12 to <18 months, and 18 to 24 months, the gross-motor quotients were 94±5, 78±11, 71±8, and 63±8, respectively, and the fine-motor quotients were 94±5, 80±10, 74±9, and 65±9, respectively. Both the gross- and fine-motor quotients significantly decreased with age (P<0.05). For the above age groups, the rates of gross-motor abnormalities were 0%, 53%, 87%, and 93%, respectively, and the rates of fine-motor development abnormalities were 0%, 47%, 67%, and 93%, respectively. The rates of gross- and fine-motor development abnormalities increased significantly with age (P<0.05). CONCLUSIONS: Children with WS have no obvious motor delays within 6 months of age, but present with decreasing motor ability and an increasing incidence of motor delays with age. Therefore, it is necessary to follow up their motor abilities and provide early intervention to decrease the incidence of motor developmental delays.

Clinical phenotypes study of 231 children with Williams syndrome in China: A single-center retrospective study.

BACKGROUND: Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by microdeletions in 7q11.23. This study aims to characterize the clinical phenotypes of Chinese children with WS to help for the early diagnosis and intervention of this disease. METHODS: 231 children diagnosed with WS were retrospectively recruited to the study. Clinical data were analyzed to obtain the incidence of different clinical phenotypes. The occurrence of phenotypes and the influence of gender and age on the incidence of different phenotypes were analyzed. RESULTS: All WS exhibited facial dysmorphism (100.0%). The majority had neurodevelopmental disorder (91.8%), hoarseness (87.4%) and cardiovascular anomalies (85.7%). The incidence of short stature (46.9%), inguinal hernia (47.2%), hypercalciuria (29.10%), hypercalcemia (9.1%), subclinical hypothyroidism (26.4%) and hypothyroidism (7.4%) were relatively higher. Gender differences were found in supravalvular aortic stenosis (SVAS, p < .001), ventricular septal defect (VSD, p < .05), inguinal hernia (p < .001), superior pulmonary stenosis (SVPS, p < .05) and neurodevelopmental disorder (p < .05). The incidence of neurodevelopmental disorder in WS increased with age (p < .05) while cardiovascular anomalies (p < .001), short stature (p < .001), hypercalciuria (p < .001) and hypercalcemia (p < .01) decreased with age. CONCLUSIONS: Facial dysmorphism, neurodevelopmental disorder, hoarseness and cardiovascular anomalies were the most common phenotypes. Genetic testing should be suggested to confirm the diagnosis for children with the above abnormalities. Gender and age should be taken into account when making diagnosis and intervention.

Analysis of The Working Performance of Large Curvature Prestressed Concrete Box Girder Bridges.

Based on numerical shape functions and the structural stressing state theory, the mechanical properties of the curved prestressed concrete box girder (CPCBG) bridge model under different loading cases are presented. First, the generalized strain energy density (GSED) obtained from the measured strain data is used to represent the stressing state pattern of the structure; then, the stressing state of the concrete section is analyzed by plotting the strain and stress fields of the bridge model. The stressing state pattern and strain fields of the CPCBG are shown to reveal its mechanical properties. In addition, the measured concrete strain data are interpolated by the non-sample point interpolation (NPI) method. The strain and stress fields of the bridge model have been plotted to analyze the stressing state of the concrete cross-section. The internal forces in the concrete sections are calculated by using interpolated strains. Finally, the torsional effects are simulated by measuring the displacements to show the torsional behavior of the cross-section. The analysis and comparison of the internal force and strain fields reveal the common and different mechanical properties of the bridge model. The results of the analysis of the curved bridge model provide a reference for the future rational design of bridge projects.

Differential Regulation of Integrin α5 and ß4 in Normal and Psoriatic Epidermal Keratinocytes

Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and ß4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and ß4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and ß4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes' α5 and ß4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes' α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed ß4. Psoriatic keratinocytes' α5 was increased by IL-13/17A, decreased by IFN-γ; but ß4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and ß4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently

A Research on Developmental Characteristics of Children With Language Delay in Zhejiang Province, China.

Study Design: We used Sign-significant relations (S-S) to assess the developmental characteristics of 1- to 4-year-old children with language delays in Zhejiang Province and to provide scientific basis for early clinical detection and comprehensive intervention. Methods: A total of 1,113 children among the ages of 1 and 4 who complained of poor language skills were assessed in language competence using S-S. These children diagnosed with language delays were divided into six groups, with each group having an age difference of 6 months. The developmental characteristics of each group were described and analyzed. Results: (1) Children from the age of 18 to 36 months were most likely to be affected by language problems, while boys were more susceptible than girls in each group. (2) There was no significant difference in the proportion of children with poor communication attitude among the groups. (3) The older the group, the higher the proportion of basic learning ability abnormality. The cutoff age for qualitative leap in the proportion of basic learning abilities was 2 years old. (4) With the increase of age, the proportion of abnormal language comprehension in each group increased gradually. The cutoff age for qualitative leap in the proportion of language comprehension was 1.5 and 2 years old. Conclusion: Language delays usually occur in children around the age of two, and as the children get older, in addition to expression of language abilities, they are more likely to have abnormal language comprehensive abilities and abnormal basic learning abilities. Based on the clinical research, we must take seriously the early screenings for this age group and conduct intervention training as soon as possible.

Indirect Regulation and Equilibrium of p35 and p40 Subunits of Interleukin (IL)-12/23 by Ustekinumab in Psoriasis Treatment.

BACKGROUND Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms. MATERIAL AND METHODS Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12th and 24th weeks of treatment). RESULTS Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection. CONCLUSIONS We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein.

Engineering Properties of Engineered Cementitious Composite and Multi-Response Optimization Using PCA-Based Taguchi Method.

The engineered cementitious composite (ECC) mixtures were prepared with Portland cement, ground fly ash, silica sand, and polyvinyl alcohol (PVA) fibers. Accordingly, four mix design factors with five levels each were designed using the Taguchi method. The engineering properties of ECC (flow expansion, compressive strength, flexural strength, charge passed, and maximum freeze-thaw cycle) were evaluated, and the single-response optimizations were conducted separately. Unlike other studies assigning a relative weighting parameter to each response, the principal component analysis (PCA) was innovatively introduced to optimize the ECC's multiple responses so that the single principal performance was obtained from the most objective perspective. Furthermore, the weighting parameters for utility concept were determined by the PCA. Thereafter, an optimum mix formulation was estimated using the PCA-based Taguchi method and the updated utility concept, which provided the most desired balance of these engineering properties. Finally, the contribution of each mix design factor to the principal performance of ECC was examined, and the estimated mix formulation was verified via an additional experiment.

Investigation on the Failure Behavior of Engineered Cementitious Composites under Freeze-Thaw Cycles.

This paper investigates the freeze-thaw performance of engineered cementitious composites (ECC) reinforced with polyvinyl alcohol (PVA) fibers, by applying an innovative criterion for judging the specimen's working state mutation. The ECC materials are prepared into 25 mixtures using the Taguchi method. Then, the fundamental transverse frequency, the flexural performance and the internal strain variation of ECC specimens subjected to freeze-thaw cycles are measured. Unlike the existing studies, this investigation focuses on the failure behavior of ECC materials in the process of freeze-thaw. The Mann-Kendall (M-K) criterion is introduced to detect the ECC specimen's working state leap feature, leading to the updated definition of frost-induced failure concept. Furthermore, the three-level model for evaluating the freeze-thaw performance of ECC materials is established according to the revealed essential leap feature. Thus, the effect of each individual mix design factor on the frost-induced failure indices is perceived from the signal-to-noise (S/N) ratio analysis and the analysis of variance (ANOVA). Finally, a mix formulation estimated based on Taguchi method is recommended for its optimum resistance against frost-induced failure, which is verified by the confirmation experiment.

Stressing State Analysis of an Integral Abutment Curved Box-Girder Bridge Model.

This paper experimentally investigates the working behavior characteristics of an integral abutment curved box-girder (IACBG) bridge model based on the structural stressing state theory. First, the stressing state of the bridge model is represented by generalized strain energy density (GSED) values at each load Fj and characterized by the normalized GSED sum Ej,norm. Then, the Mann-Kendall (M-K) criterion is adopted to detect the stressing state mutations of the bridge model from Ej,norm-Fj curve in order to achieve the new definition of structural failure load. Correspondingly, the stressing state modes for the bridge model's sections and internal forces are reached in order to investigate their variation characteristics and the coordinated working behavior around the updated failure load. The unseen knowledge is revealed by studying working behavior characteristics of the bridge model. Therefore, the analytical results could provide a new structural analysis method, which updates the definition of the existing structural failure load and provides a reference for future design of the bridges.

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Analysis of plasma proteome from cases of the different traditional Chinese medicine syndromes in patients with chronic hepatitis B.

A proteomic analysis method, two dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF-MS), was used to explore the link between plasma proteome and the different syndromes of traditional Chinese medicine (TCM) in patients with chronic hepatitis B (CHB). In compared with the plasma proteomes from health donors, the alterations in protein expression from cases of the five TCM syndromes, including damp heat stasis in the middle-Jiao syndrome, liver Qi stagnation and spleen deficiency syndrome, spleen and kidney Yang deficiency syndrome, liver and kidney Yin deficiency syndrome, and blood stasis into collateral syndrome with CHB were identified (P<0.05). In the cases of the five TCM syndromes with CHB, immunoglobulin J-chains (IGJ) and C-reactive protein (CRP) were up-regulated, while haptoglobin (HPT), retinol binding protein (RBP) and vitronectin were down-regulated. To further confirm these results, four proteins, including CRP, IGJ, HPT and RBP, from more plasma samples were quantified by ELISA. The results showed that the changes of protein levels were consistent with those from the 2-DE experiment. Importantly, the upregulation tendency of IGJ level in plasma is related with the different TCM syndromes with CHB (P<0.05). Our results show that IGJ may serve as a novel potential biomarker for diagnosis of the different TCM syndromes in patients with CHB.