Enhancement of hyaline cartilage and subchondral bone regeneration in a rat osteochondral defect model through focused extracorporeal shockwave therapy.

Aims: To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-ß, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods: The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results: In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-ß, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion: ESWT promoted the effect of TGF-ß/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model.

Netographic narratives of user-generated travelogues on tourist destination image of Thailand.

The image of a tourist destination is considered a vital aspect of international travel experiences, yet research in this area remains limited. Adopting a combination of netography and qualitative research methodology, this study aims to contribute to the scientific knowledge of destination image development in Thailand by analysing online travelogues to evaluate how Chinese tourists interpret the idea of destination image. To achieve this goal, 146,641 words of Chinese internet comments containing the keyword "Thailand" from four major media sources and Chinese bloggers were gathered and analysed using netography methodology. The findings showed that there was a rise in public interest, in public forums, in the destination image of Thailand among Chinese outbound tourists. The study's results may provide important fundamental theoretical insights and inspire further investigation into the issue of destination image construction.

Sleep and internalizing problems in primary school children with attention-deficit hyperactivity disorder.

BACKGROUND: Internalizing and externalizing problems have received great attention, and children with ADHD exhibit high rates of comorbid internalizing and externalizing disorders. This study aimed to explore the relationship between sleep and internalizing problems in children with attention-deficit hyperactivity disorder (ADHD) and the probable mediating role of externalizing problems. METHODS: A total of 203 primary school children diagnosed with ADHD for the first time were recruited for this study. Children with ADHD were evaluated by Children's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ). Internalizing problems were represented by emotional symptoms and peer problems of SDQ, and externalizing problems were represented by conduct problems and hyperactivity-inattention problems of SDQ. Multi-step linear regression analysis was used to investigate the mediating effect of externalizing problems on the relationship between sleep and internalizing problems. RESULTS: Sleep in children with ADHD was associated with emotional problems in internalizing problems, and conduct problems in externalizing problems mediated the association between sleep and emotional problems. CONCLUSION: For children with ADHD, when it is difficult to identify internalizing problems, especially emotional problems, we can take sleep and externalizing problems as clues to improve our clinical ability to recognize and deal with emotional problems. IMPACT: 1. We first explored the possible mediating role of conduct problems between sleep and emotional problems in primary school children with ADHD. 2. When it is difficult to identify internalizing problems, especially emotional problems, we can take sleep and externalizing problems as clues to improve our clinical ability to recognize emotional problems for children with ADHD. 3. For children with ADHD with potential internalizing problems, especially emotional problems, interventions for their sleep and externalizing problems may be the possible methods to deal with.

Geometric lightguide for near-eye light field displays.

Most near-eye displays with one fixed focal plane suffer from the vergence-accommodation conflict and cause visual discomfort to users. In contrast, light field displays can provide natural and comfortable 3D visual sensation to users without the conflict. This paper presents a near-eye light field display consisting of a geometric lightguide and a light field generator, along with a collimator to ensure the light rays propagating in the lightguide are collimated. Unlike most lightguides, which reduce thickness by employing total internal reflection that can easily generate stray light, our lightguide directly propagates light rays without total internal reflection. The partially reflective mirrors of the lightguide expand the exit pupil to achieve an eyebox of 13m m(h o r i z o n t a l)×6.5m m(v e r t i c a l) with an eye relief of 18 mm. The collimator and the light field generator, both having effective focal lengths different in the horizontal and vertical directions, are designed to provide a 40-deg diagonal field of view. The working range of the light field generator, which is 30 cm to infinity, is verified qualitatively and quantitatively by experiments. We optimize the illuminance uniformity and analyze the illuminance variation across the eyebox. Further, we minimize the ghost artifact (referring to the split-up of light fields replicated by the partially reflective mirrors) by orienting the partially reflective mirrors at slightly different angles to enhance the image quality for short-range applications such as medical surgery.

Offspring's own serotonin transporter genotype, independently from the maternal one, increases anxiety- and depression-like behavior and alters neuroplasticity markers in rats.

INTRODUCTION: Developmental changes due to early life variations in the serotonin system affect stress-related behavior and neuroplasticity in adulthood. These outcomes can be caused both by offspring's own and maternal serotonergic genotype. We aimed to dissociate the contribution of the own genotype from the influences of mother genotype. METHODS: Sixty-six male homozygous (5-HTT-/-) and heterozygous (5-HTT+/-) serotonin transporter knockout and wild-type rats from constant 5-HTT genotype mothers crossed with varying 5-HTT genotype fathers were subjected to tests assessing anxiety- and depression-like behaviors. Additionally, we measured plasma corticosterone levels and mRNA levels of BDNF, GABA system and HPA-axis components in the prelimbic and infralimbic cortex. Finally, we assessed the effect of paternal 5-HTT genotype on these measurements in 5-HTT+/- offspring receiving their knockout allele from their mother or father. RESULTS: 5-HTT-/- offspring exhibited increased anxiety- and depression-like behavior in the elevated plus maze and sucrose preference test. Furthermore, Bdnf isoform VI expression was reduced in the prelimbic cortex. Bdnf isoform IV and GABA related gene expression was also altered but did not survive false discovery rate (FDR) correction. Finally, 5-HTT+/- offspring from 5-HTT-/- fathers displayed higher levels of anxiety- and depression-like behavior and changes in GABA, BDNF and HPA-axis related gene expression not surviving FDR correction. LIMITATIONS: Only male offspring was tested. CONCLUSIONS: Offspring's own 5-HTT genotype influences stress-related behaviors and Bdnf isoform VI expression, independently of maternal 5-HTT genotype. Paternal 5-HTT genotype separately influenced these outcomes. These findings advance our understanding of the 5-HTT genotype dependent susceptibility to stress-related disorders.

Analysis of mental health status and related factors in patients with acute cerebral infarction.

BACKGROUND: Acute cerebral infarction (ACI) is characterized by a high incidence of morbidity, disability, recurrence, death and heavy economic burden, and has become a disease of concern in global researchers. As ACI has serious effects on patients' physical status, life and economy, often causing anxiety, depression and other psychological problems, these problems can lead to the aggravation of physical symptoms; thus, it is very important to understand the factors affecting the mental health of these patients. AIM: To understand the elements that affect the mental health of patients who have suffered an ACI. METHODS: A questionnaire survey was conducted among patients with ACI admitted to three tertiary hospitals (Quanzhou First Hospital, Fuqing City Hospital Affiliated to Fujian Medical University, and the 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China) in Fujian Province from January 2022 to December 2022 using the convenience sampling method. ACI inpatients who met the inclusion criteria were selected. Informed consent was obtained from the patients before the investigation, and a face-to-face questionnaire survey was conducted using a unified scale. The questionnaire included a general situation questionnaire, Zung's self-rating depression scale and Zung's self-rating anxiety scale. All questionnaires were checked by two researchers and then the data were input and sorted using Excel software. The general situation of patients with ACI was analyzed by descriptive statistics, the influence of variables on mental health by the independent sample t test and variance analysis, and the influencing factors on psychological distress were analyzed by multiple stepwise regression. RESULTS: The average age of the 220 patients with ACI was 68.64 ± 10.74 years, including 142 males and 78 females. Most of the patients were between 60 and 74 years old, the majority had high school or technical secondary school education, most lived with their spouse, and most lived in cities. The majority of patients had a personal income of 3001 to 5000 RMB yuan per month. The new rural cooperative medical insurance system had the largest number of participants. Most stroke patients were cared for by their spouses and of these patients, 52.3% had previously smoked. Univariate analysis showed that gender, age, residence, course of disease, number of previous chronic diseases and smoking history were the main factors affecting the anxiety scores of patients with ACI. Age, living conditions, monthly income, course of disease and knowledge of disease were the primary variables influencing the depression score in patients with ACI. The findings of multivariate analysis revealed that the course of disease and gender were the most important factors influencing patients' anxiety scores, and the course of disease was also the most important factor influencing patients' depression scores. CONCLUSION: Long disease course and female patients with ACI were more likely to have psychological problems such as a high incidence of emotional disorders. These groups require more attention and counseling.

Towards improved screening of toxins for Parkinson's risk.

Parkinson's disease (PD) is a chronic, progressive and disabling neurodegenerative disorder. The prevalence of PD has risen considerably over the past decades. A growing body of evidence suggest that exposure to environmental toxins, including pesticides, solvents and heavy metals (collectively called toxins), is at least in part responsible for this rapid growth. It is worrying that the current screening procedures being applied internationally to test for possible neurotoxicity of specific compounds offer inadequate insights into the risk of developing PD in humans. Improved screening procedures are therefore urgently needed. Our review first substantiates current evidence on the relation between exposure to environmental toxins and the risk of developing PD. We subsequently propose to replace the current standard toxin screening by a well-controlled multi-tier toxin screening involving the following steps: in silico studies (tier 1) followed by in vitro tests (tier 2), aiming to prioritize agents with human relevant routes of exposure. More in depth studies can be undertaken in tier 3, with whole-organism (in)vertebrate models. Tier 4 has a dedicated focus on cell loss in the substantia nigra and on the presumed mechanisms of neurotoxicity in rodent models, which are required to confirm or refute the possible neurotoxicity of any individual compound. This improved screening procedure should not only evaluate new pesticides that seek access to the market, but also critically assess all pesticides that are being used today, acknowledging that none of these has ever been proven to be safe from a perspective of PD. Importantly, the improved screening procedures should not just assess the neurotoxic risk of isolated compounds, but should also specifically look at the cumulative risk conveyed by exposure to commonly used combinations of pesticides (cocktails). The worldwide implementation of such an improved screening procedure, would be an essential step for policy makers and governments to recognize PD-related environmental risk factors.

Activated Wake Systems in Narcolepsy Type 1.

OBJECTIVE: Narcolepsy type 1 (NT1) is assumed to be caused solely by a lack of hypocretin (orexin) neurotransmission. Recently, however, we found an 88% reduction in corticotropin-releasing hormone (CRH)-positive neurons in the paraventricular nucleus (PVN). We assessed the remaining CRH neurons in NT1 to determine whether they co-express vasopressin (AVP) to reflect upregulation. We also systematically assessed other wake-systems, since current NT1 treatments target histamine, dopamine, and norepinephrine pathways. METHODS: In postmortem tissue of people with NT1 and matched controls, we immunohistochemically stained and quantified neuronal populations expressing: CRH and AVP in the PVN, and CRH in the Barrington nucleus; the key neuronal histamine-synthesizing enzyme, histidine decarboxylase (HDC) in the hypothalamic tuberomammillary nucleus (TMN); the rate-limited-synthesizing enzyme, tyrosine hydroxylase (TH), for dopamine in the mid-brain and for norepinephrine in the locus coeruleus (LC). RESULTS: In NT1, there was: a 234% increase in the percentage of CRH cells co-expressing AVP, while there was an unchanged integrated optical density of CRH staining in the Barrington nucleus; a 36% increased number of histamine neurons expressing HDC, while the number of typical human TMN neuronal profiles was unchanged; a tendency toward an increased density of TH-positive neurons in the substantia nigra compacta; while the density of TH-positive LC neurons was unchanged. INTERPRETATION: Our findings suggest an upregulation of activity by histamine neurons and remaining CRH neurons in NT1. This may explain earlier reports of normal basal plasma cortisol levels but lower levels after dexamethasone suppression. Alternatively, CRH neurons co-expressing AVP neurons are less vulnerable. ANN NEUROL 2023;94:762-771.

The challenges of screen time in children with typical development and children with developmental disorders during COVID-19 pandemic.

Background: The significant lifestyle changes that occurred during the lockdown period associated with the COVID-19 pandemic may have had many potential adverse effects on children, in particular, sedentary screen exposure among children, including those with developmental disorders. We conducted a cross-sectional study to investigate and compare the screen time and outdoor activity time of children with typically development (TD) and those with developmental disorders during and before the emergence of COVID-19, and identified the risk factors related to screen time during the COVID-19 pandemic. Methods: A total of 496 children were surveyed via online questionnaires. Parents or/and children filled in the online questionnaire, including basic characteristics, screen time, outdoor activity time, and other related factors. The Statistical Product and Service Solutions software was used to analyze all data. Results: Children spent less time outdoors (t=14.774, P<0.001) and more time on electronic screens (t=-14.069, P<0.001) during the lockdown period of COVID-19, compared to the periods before COVID-19. Age (P=0.037), pre-COVID-19 screen time (P=0.005), screen time used for learning/education (P<0.001), screen time of siblings (P=0.007), and use of screen devices as electronic babysitters (P=0.005) were risk factors for screen time during the COVID-19 pandemic, while restrictive use of electronic devices by parents (P<0.05) was a protective factor. The screen time of children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) was significantly longer than children with TD before COVID-19 pandemic, but there is no statistical difference during the COVID-19 pandemic. Conclusions: During the COVID-19 pandemic, children's screen exposure time increased, and outdoor activities decreased significantly. This represents a significant challenge, and we should focus our efforts on managing children's screen time and promoting healthier lifestyles, including children with typical development, as well as those with developmental disorders.

Pipkin Type I and II femoral head fractures: internal fixation or excision?-from the hip arthroscopy perspective.

The treatment of patients with femoral head fractures with regard to fixation versus excision is controversial. This study aimed to compare the results of fixation and excision in hip arthroscopy-assisted surgery. This retrospective study included adult patients with femoral head fractures who were treated with hip arthroscopy surgery from March 2016 to April 2020, with a minimum follow-up of 24 months. The patients were divided into two groups: Group 1 (fixation group) and Group 2 (excision group). To compare the therapeutic effects between the two groups, clinical and radiographic outcomes, operative time, pain score, length of hospital stay after surgery and related complications were investigated. There were 13 (mean duration, 47.5 months; range, 24-72 months) and 8 (mean duration, 48.6 months; range, 26-74 months) patients in the fixation and excision groups, respectively. The excision group had better functional results than the fixation group in terms of the median modified Harris hip score (P = 0.009). No significant differences were observed in operative time, pain score or hospital stay after surgery between the two groups. Further, no osteonecrosis of the femoral head or traumatic arthritis occurred in either group. A piece of fracture fragment >2 cm can be considered for hip arthroscopy-assisted internal fixation, whereas the others can be removed. The excision group had better outcomes than the fixation group. Hence, hip arthroscopy-assisted internal fixation or excision of bony fragments led to satisfactory short-term clinical and radiological results for the treatment of Pipkin Type I and II femoral head fractures.

Isoalantolactone mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin.

Isoalantolactone (Iso) is a bioactive lactone isolated from the root of Inula helenium L, which has been reported to have many pharmacological effects. To investigate the role and mechanism of isoalantolactone in chronic myeloid leukemia (CML), we first investigated isoalantolactone's anti-proliferative effects on imatinib-sensitive and imatinib-resistant CML cells by CCK8. Flow cytometry was used to detect isoalantolactone-induced cell apoptosis. Survivin was overexpressed in KBM5 and KBM5T315I cells using the lentivirus vector pSIN-3×flag-PURO. In KBM5 and KBM5T315I cells, shRNA was used to knockdown survivin. Cellular Thermal Shift Assay (CETSA) was used to detect the interaction between isoalantolactone and survivin. The ubiquitin of survivin induced by isoalantolactone was detected through immunoprecipitation. Quantitative polymerase-chain reaction (Q-PCR) and western blotting were used to detect the levels of mRNA and protein. Isoalantolactone inhibits the proliferation and promotes apoptosis of imatinib-resistant CML cells. Although isoalantolactone inhibits the proteins of BCR-ABL and survivin, it cannot inhibit survivin and BCR-ABL mRNA levels. Simultaneously, it was shown that isoalantolactone can degrade survivin protein by increasing ubiquitination. It was demonstrated that isoalantolactone-induced survivin mediated downregulation of BCR-ABL protein. It was also revealed that isoalantolactone triggered BCR-ABL protein degradation via caspase-3. Altogether, isoalantolactone inhibits survivin through the ubiquitin proteasome pathway, and mediates BCR-ABL downregulation in a caspase-3 dependent manner. These data suggest that isoalantolactone is a natural compound, which can be used as a potential drug to treat TKI-resistant CML.

Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.

Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to Hcrt, Qrfp transcript is also lost in the lateral hypothalamus, while in mice where only the Hcrt gene is inactivated Qrfp is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved QRFP expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the HCRT gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT, CRH and Dynorphin (PDYN) gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that HCRT, PDYN, and CRH are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy.

The association of vitamin A, zinc and copper levels with clinical symptoms in children with autism spectrum disorders in Jilin Province, China.

BACKGROUND: This study evaluated vitamin A (VA), copper (Cu), and zinc (Zn) levels in the population with autism spectrum disorder (ASD) in Jilin Province, China. Furthermore, we examined their links to core symptoms and neurodevelopment, as well as gastrointestinal (GI) comorbidities and sleep disorders. METHODS: This study included 181 children with autism and 205 typically developing (TD) children. The participants had not taken vitamin/mineral supplements in the prior three months. High-performance liquid chromatography was used to measure serum VA levels. By using inductively coupled plasma-mass spectrometry, Zn and Cu concentrations in plasma were determined. Importantly, the Childhood Autism Rating Scale, the Social Responsiveness Scale, and the Autism Behavior Checklist were used to measure core ASD symptoms. However, the Griffith Mental Development Scales-Chinese were used to measure neurodevelopment. GI comorbidities and sleep abnormalities were assessed with the 6 Item-Gastrointestinal Severity Index and Children's Sleep Habits Questionnaire, respectively. Children with ASD with GI issues were grouped according to severity (low GI severity and high GI severity groups). RESULTS: (i) The difference in VA, Zn, Cu levels and the Zn/Cu ratio between ASD and TD children is small. But children with ASD had lower VA levels and Zn/Cu ratio, higher Cu levels than TD children. Cu levels in children with ASD were associated with the severity of core symptoms. (ii) Children with ASD were much more likely than their TD counterparts to suffer from GI comorbidities or sleep problems. Furthermore, it was observed that high GI severity was associated with lower levels of VA, whereas low GI severity was associated with higher levels of VA. (iii) The children with ASD who had both lower VA and lower Zn/Cu ratio had more severe scores on the Autism Behavior Checklist, but not on other measures. CONCLUSION: Children with ASD had lower VA and Zn/Cu ratio, and higher Cu levels. Cu levels in children with ASD were weakly correlated with one subscale on social or self-help. ASD children with lower VA levels may face more serious GI comorbidities. Children with ASD combined VA-Zn/Cu lower had more severe core symptoms. TRIAL REGISTRATION: Registration number: ChiCTR-OPC-17013502. Date of registration: 2017-11-23.

Spatial-temporal evolution and convergence analysis of agricultural green total factor productivity-evidence from the Yangtze River Delta Region of China.

Measuring regional differences in agricultural green total factor productivity (AGTFP) provides a basis for policy guidance on agricultural green development in the Yangtze River Delta (YRD) region. By constructing a two-period Malmquist-Luenberger index under the carbon emission constraint, we measure the AGTFP of cities in the YRD region from 2001 to 2019. Furthermore, adopting the Moran index method and the hot spot analysis method, this paper analyzes the global spatial correlation and local spatial correlation of AGTFP in this region. Moreover, we investigate its spatial convergence. The results show that the AGTFP of 41 cities in the YRD region is on an increasing trend; the growth of AGTFP in the eastern cities is mainly driven by green technical efficiency, while this growth in the southern cities is mainly stimulated by green technical efficiency and green technological progress. We also find a significant spatial correlation between cities' AGTFP in the YRD region from 2001 to 2019, but with certain fluctuations, showing a U-shaped trend of "strong-weak-strong". In addition, absolute ß convergence of the AGTFP exists in the YRD region, and this convergence speed is accelerated with the addition of spatial factors. This evidence provides support for implementing the regional integration development strategy and optimizing the regional agricultural spatial layout. Our findings offer implications for promoting the transfer of green agricultural technology to the southwest of the YRD region, strengthening the construction of agricultural economic belts and agricultural economic circles, and improving the efficiency of agricultural resource use.

Risk factors for developmental quotients in ASD children: A cross-sectional study.

Objective: To analyze the risk factors for developmental quotients (DQs) of children with autism spectrum disorder (ASD) and to better understand the effects of screen time on neurodevelopment in children with ASD. Methods: We retrospectively analyzed the data of 382 children with ASD, including demographic profiles; socioeconomic status; score on the Chinese parent-child interaction scale (CPCIS); screen time questionnaire; ASD symptom rating scales, including the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Autism Diagnostic Observation Schedule Second Edition (ADOS-2); and DQs using Griffiths Development Scales-Chinese Edition. Univariate analysis was carried out to analyze the factors related to the DQs of children with ASD, and then the linear regression model was used to identify the independent influencing factors of the DQs of children with ASD. Results: Vitamin D (ß = 0.180, p = 0.002), age (ß = -0.283, p = 0.000) and CARS score (ß = -0.347, p = 0.000) are risk factors related to DQ of locomotor in children with ASD. Vitamin D (ß = 0.108, p = 0.034), CARS score (ß = -0.503, p = 0.000), ADOS-2 severity score (ß = -0.109, p = 0.045) and CPCIS score (ß = 0.198, p = 0.000) are risk factors related to DQ of personal social skill in children with ASD. Vitamin D (ß = 0.130, p = 0.018), CARS score (ß = -0.469, p = 0.000), and CPCIS score (ß = 0.133, p = 0.022) are risk factors related to DQ of hearing-speech in children with ASD. Vitamin D (ß = 0.163, p = 0.003) and CARS score (ß = -0.471, p = 0.000) are risk factors related to DQ of eye-hand coordination in children with ASD. Age (ß = -0.140, p = 0.020), CARS score (ß = -0.342, p = 0.000), ADOS-2 severity score (ß = -0.133, p = 0.034) and CPCIS score (ß = 0.193, p = 0.002) are risk factors related to DQ of performance in children with ASD. Vitamin D (ß = 0.801, p = 0.000) and CPCIS score (ß = 0.394, p = 0.019) are risk factors related to DQ of practical reasoning in children with ASD. Conclusion: Vitamin D status, the severity of autistic symptoms and parent-child interaction are risk factors for developmental quotients in children with ASD. Screen exposure time is negatively associated with DQs in children with ASD but is not an independent risk factor for DQs.

A high performance liquid chromatography tandem mass spectrometry protocol for detection of neurotransmitters in the rat brain tissue.

The detection of neurotransmitters has extensively been applied to the study of the pathogenesis, diagnosis, and therapeutic effect of drugs on many neuropsychiatric diseases. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been employed to determine neurotransmitters levels due to its distinct advantages. However, neurotransmitter detection still presents some challenges. A rapid and sensitive HPLC-MS/MS protocol has been established in our lab, which can simultaneously detect 5 neurotransmitters with an easy pretreatment procedure. The protocol provides demanded reference value for the lab using an Agilent HPLC-MS/MS system with a triple quadrupole analyzer.

Novel de novo ZNF148 truncating variant causing autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability.

ZNF148 gene is a Krüppel-type transcription factor that has transcriptional regulatory function. Heterozygous variant in ZNF148 gene causes an intellectual disability syndrome characterized by global developmental delay, absence, or hypoplasia of corpus callosum, wide intracerebral ventricles, and dysmorphic facial features, while its associations with ASD and ADHD have not been reported. We report a new patient with intellectual disability, autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). The patient had a novel heterozygous truncating variant c.1818dupC (p.Lys607Glnfs*11) in the ZNF148 gene. This variation produces a ZNF148 truncated protein with a deletion of the C-terminal activation domain and may destabilize the protein by affecting the transcriptional activation function. Brain MRI shows normal brain development. Here, we identify a novel ZNF148 heterozygous truncating variant in a patient with distinct phenotypes of ASD and ADHD, which expands the genotype-phenotype spectrum of ZNF148, and indicates ZNF148 is also a potential target gene for ASD.

Analysis of scores of Symptom Checklist 90 (SCL-90) questionnaire of 182 parents of children with spinal muscular atrophy: a cross-sectional study.

Background: Spinal muscular atrophy (SMA) is a hereditary disorder characterized by progressive muscle weakness and atrophy in children. However, less attention is paid to psychiatric symptoms of SMA parents. Attention to the psychiatric symptoms of parents of SMA children can improve the comprehensiveness of family support for SMA children, which is beneficial to the rehabilitation of SMA children. Here, we conducted a survey on the psychiatric symptoms of SMA parents and analyzed its relevant factors, with an attempt to inform the psychological support for SMA parents. Methods: The Symptom Checklist 90 (SCL-90) and a self-designed basic information (such as parent's gender, household area, place of residence, education background, etc.) questionnaire (in electronic questionnaire) were distributed to parents of SMA children aged 0-18 in a charity WeChat group sponsored by the Meier Advocacy & Support Center for SMA during the period from August 1 to August 31, 2021. Parents completed the electronic questionnaires by mobile phone or computer voluntarily. A total of 188 questionnaires were obtained, of which 182 were valid. Comparisons were performed with the SCL-90 adult norms as the standards. The potential correlations between the general data of SMA parents and children and abnormal factors in the SCL-90 for SMA parents were analyzed. Results: The SCL-90 factors somatization (1.56±0.80, P=0.002), depression (1.78±0.98, P<0.001), anxiety (1.58±0.87, P=0.007), fear (1.39±0.74, P=0.003), and sleep and eating problems (1.67±0.87, P=0.014) of SMA parents were significantly higher than the national norms. Place of residence was correlated with sleep and eating problems (r=0.158, P=0.033). Increasing age [odds ratio (OR) =1.012, P=0.014] and continuous home-living status (OR =0.360, P=0.031) of SMA children increased the risk of depression in their parents, and the lack of rehabilitation management in SMA children increased the risk of anxiety of their parents (OR =0.409, P=0.038). Non-urban residence (OR =2.602, P=0.017) and poor physical health (OR =0.163, P=0.031) were the relevant factors for the increased risk of sleep and eating problems in SMA parents. Conclusions: SMA parents have a higher risk of developing psychiatric symptoms problems compared with the general population. Increasing age and the continuous home-living status of SMA children increase the risk of depression in their parents, and the lack of rehabilitation management increase the risk of anxiety in SMA parents.

Effect of three clinical therapies on cytokines modulation in the hip articular cartilage and bone improvement in rat early osteonecrosis of the femoral head.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) and adipose-derived mesenchymal stem cells (ADSCs) have been used clinically for the treatment of osteonecrosis of the femoral head (ONFH). The study elucidated that ESWT, ADSCs, and combination therapy modulated pro-inflammatory cytokines in the articular cartilage and subchondral bone of early rat ONFH. METHODS: ESWT and ADSCs were prepared and isolated for treatment. Micro-CT, pathological analysis, and immunohistochemistry were performed and analysed. RESULTS: After treatments, subchondral bone of ONFH was improved in trabecular bone volume (BV/TV) (p < 0.001), thickness (Tb.Th) (p < 0.01 and 0.001), and separation (Tb.Sp) (p < 0.001) and bone mineral density (BMD) (p < 0.001) using micro-CT analysis. The articular cartilage was protected and decreased apoptosis markers after all the treatments. The expression of IL33 (p < 0.001), IL5 (p < 0.001), IL6 (p < 0.001), and IL17A (p < 0.01) was significantly decreased in the ESWT, ADSCs, and Combination groups as compared with ONFH group. The IL33 receptor ST2 was significantly increased after treatment (p < 0.001) as compared with ONFH group. The Combination group (p < 0.01) decreased the expression of IL6 better than the ESWT and ADSCs groups. CONCLUSION: ESWT, ADSCs and combination therapy significantly protected articular cartilage and subchondral bone of early rat ONFH by modulating the expression of pro-inflammatory cytokines including, IL33 and its receptor ST2, IL5, IL6, and IL17A.

Feeding problems, age of introduction of complementary food and autism symptom in children with autism spectrum disorder.

In this cross-sectional study, 84 children with autism spectrum disorder (ASD) and 77 healthy subjects showing typical development (TD) were reviewed. Parents reviewed the age of introduction of complementary foods (CFs), completed a demographic, diet behavior questionnaire and the Autism Behavior Checklist (ABC). The results showed that the age of introduction of CFs was later in children with ASD than their TD counterparts. The age of introduction of CFs in ASD group was positively correlated with feeding problem. While the correlation was not observed in TD group. Children in the ASD group had higher total scores of the diet behavior questionnaire and all four subdomains (poor eating ability, mealtime eating behavior, food selectivity, and parental feeding behavior). ASD symptoms were clearly associated with feeding problems. The sensory subdomain score in ABC was positively correlated with poor eating ability, mealtime behavior and total score of the diet behavior questionnaire. The social self-care subdomain score was positively correlated with food selectivity. The interaction subdomain score was negative correlated with parental feeding behavior and total score of the diet behavior questionnaire. Further studies are required to establish the utility of delayed CFs introduction and/or early feeding problems as potential indicators of ASD.