Kewen Jiang

Background: Despite advancements in public health awareness in China, pediatric drowning remains a significant concern with no marked decline in incidence. This study is to explore the changes in the epidemiological characteristics of children drowning. Methods: We retrospectively analyzed the clinical data of 296 drowning children who received treatment from January 2010 to December 2021. Results: We found that 1–3-year-old male children have the highest incidence of drowning in the afternoon of summer, especially in natural water in rural areas, which are more dangerous than swimming pools. The pre hospital cardiopulmonary resuscitation (CPR) time and drowning time are significantly associated with the outcome of the patient. In children without clear drowning time, our study found that clinical indicators such as Glasgow Coma Scale (GCS) score, blood lactate level, blood pH value, and blood glucose have a certain association with the outcomes of the children. The occurrence of child drowning incidents did not show significant changes due to the COVID-19 pandemic or the national control measures. Conclusions: Pediatric drowning persists as a critical public health issue, with rural areas posing the greatest risk. Early rescue and high-quality basic life support are key to improving outcomes. Targeted prevention strategies should prioritize rural water safety and caregiver education, while clinical indicators may aid in assessment of outcomes when drowning history is unavailable.

Fyn‐related kinase (FRK), which belongs to the Src family of non‐receptor protein tyrosine kinases, functions during the cell cycle. Here, we report an autistic patient with an intragenic mutation of FRK and two other autism‐related genes. Circumventing the barrier of murine model studies, we generated the CRISPR/Cas9‐engineered frk ^−/− zebrafish. We found that frk ‐knockout led to early developmental abnormalities. Frk ^−/− fish exhibited autism‐like behavior, including impaired social communication, repetitive stereotypic behavior, altered anxiety level, and cognitive dysfunction in both larvae and adults, which could be rescued by the transgenic neuron‐specific re‐expression of frk . GO and KEGG analysis of RNA‐sequencing data found that the frk ‐knockout‐induced DEGs were mainly concentrated in processes and functions related to cell metabolism. PPI network analysis of the detected DEGs suggested that the cyp24a1/tp53 pathway may play a key role in frk ‐knockout‐induced autism. Furthermore, we found that the numbers of BrdU ⁺ cells were significantly increased in the frk ^−/− larval brains. Inhibition of Cyp24a1 or activation of tp53 reduced cell proliferation and partially ameliorated social impairments in frk ^−/− zebrafish. Overall, our work established an autism model of frk ‐knockout with an assessable behavior phenotype in zebrafish and provided key insights into cell proliferation and the influence of the cyp24a1/tp53 pathway‐regulated cell proliferation on frk ‐knockout‐induced autism‐like behaviors.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder associated with broad functional impairments in children. As a cri

Background: The digital therapy of attention-deficit/hyperactivity disorder (ADHD) based on a “self-adaptive multitasking training paradigm” has been developed to improve the cognitive functional impairments and attention deficits of children with ADHD. However, the efficacy and safety of such treatment for Chinese patients remain untested. Objective: This study aimed to preliminarily evaluate the actual intervention effects of a video game–like training software (ADHD-DTx) for children with ADHD aged 6-12 years as the first nationally certified digital therapeutics medical device for ADHD in China. We performed a single-arm, open-label efficacy and safety study. Methods: This is a single-arm, open-label, pre-post efficacy and safety study. A total of 97 participants were included in the analysis. Participants received digital therapy (ADHD-DTx) and basic behavioral parent training for 4 weeks (25 min/day, ≥5 times/week) without medication. The efficacy outcomes included the Test of Variables of Attention (TOVA), Swanson, Nolan, and Pelham Questionnaire, version 4 (SNAP-IV), Weiss Functional Impairment Rating Scale (WFIRS), and Conner’s Parent Symptom Questionnaire (PSQ). Safety-related events were monitored during and after the trial. Results: From day 0 (baseline) to day 28, the population TOVA Attention Performance Index exhibited statistically significant improvement (from mean –4.15, SE of the mean [SEM] 0.32 to mean –1.70, SEM 0.30; t94=–8.78; n=95; P<.001); the population total, inattention (AD), hyperactivity/impulsivity (HD), and oppositional defiant disorder (ODD) scores of SNAP-IV all significantly improved (total: from mean 1.33, SEM 0.05 to mean 1.09, SEM 0.05; t96=5.32; P<.001; AD: from mean 1.71, SEM 0.06 to mean 1.44, SEM 0.06; t96=4.44; P<.001; HD: from mean 1.38, SEM 0.07 to mean 1.05, SEM 0.06; t96=5.96; P<.001; ODD: mean 0.84, SEM 0.05 to mean 0.75, SEM 0.05; Z=2.47; P=.03; n=97); for WFIRS results, domains of “family” and “social activities” showed significant population improvement (family: from mean 0.75, SEM 0.05 to mean 0.65, SEM 0.04; Z=2.80; P=.01; social activities: from mean 0.56, SEM 0.05 to mean 0.45, SEM 0.05; Z=2.91; P=.01; n=97); for PSQ results, domains of “learning problem,” “psychosomatic problem,” “impulsivity-hyperactivity,” and “hyperactivity index” showed significant improvement (learning problem: from mean 1.72, SEM 0.06 to mean 1.57, SEM 0.06; Z=2.42; P=.03; psychosomatic problem: from mean 0.40, SEM 0.03 to mean 0.32, SEM 0.03; Z=2.66; P=.02; impulsivity-hyperactivity: from mean 0.94, SEM 0.06 to mean 0.80, SEM 0.06; Z=2.49; P=.03; hyperactivity index: from mean 1.06, SEM 0.05 to mean 0.92, SEM 0.05; Z=2.90; P=.01; n=97). No device-related adverse event or severe adverse event was observed or reported during or after the intervention. Conclusions: This study preliminarily suggested the significant improvements of ADHD symptoms and attention function after 4 weeks of ADHD-DTx digital therapy combining basic behavioral parent training with satisfying safety outcomes.

BACKGROUND The digital therapy of attention-deficit/hyperactivity disorder (ADHD) based on a “self-adaptive multitasking training paradigm” has been developed to improve the cognitive functional impairments and attention deficits of children with ADHD. However, the efficacy and safety of such treatment for Chinese patients remain untested. OBJECTIVE This study aimed to preliminarily evaluate the actual intervention effects of a video game–like training software (ADHD-DTx) for children with ADHD aged 6-12 years as the first nationally certified digital therapeutics medical device for ADHD in China. We performed a single-arm, open-label efficacy and safety study. METHODS This is a single-arm, open-label, pre-post efficacy and safety study. A total of 97 participants were included in the analysis. Participants received digital therapy (ADHD-DTx) and basic behavioral parent training for 4 weeks (25 min/day, ≥5 times/week) without medication. The efficacy outcomes included the Test of Variables of Attention (TOVA), Swanson, Nolan, and Pelham Questionnaire, version 4 (SNAP-IV), Weiss Functional Impairment Rating Scale (WFIRS), and Conner’s Parent Symptom Questionnaire (PSQ). Safety-related events were monitored during and after the trial. RESULTS From day 0 (baseline) to day 28, the population TOVA Attention Performance Index exhibited statistically significant improvement (from mean –4.15, SE of the mean [SEM] 0.32 to mean –1.70, SEM 0.30; t94=–8.78; n=95; P<.001); the population total, inattention (AD), hyperactivity/impulsivity (HD), and oppositional defiant disorder (ODD) scores of SNAP-IV all significantly improved (total: from mean 1.33, SEM 0.05 to mean 1.09, SEM 0.05; t96=5.32; P<.001; AD: from mean 1.71, SEM 0.06 to mean 1.44, SEM 0.06; t96=4.44; P<.001; HD: from mean 1.38, SEM 0.07 to mean 1.05, SEM 0.06; t96=5.96; P<.001; ODD: mean 0.84, SEM 0.05 to mean 0.75, SEM 0.05; Z=2.47; P=.03; n=97); for WFIRS results, domains of “family” and “social activities” showed significant population improvement (family: from mean 0.75, SEM 0.05 to mean 0.65, SEM 0.04; Z=2.80; P=.01; social activities: from mean 0.56, SEM 0.05 to mean 0.45, SEM 0.05; Z=2.91; P=.01; n=97); for PSQ results, domains of “learning problem,” “psychosomatic problem,” “impulsivity-hyperactivity,” and “hyperactivity index” showed significant improvement (learning problem: from mean 1.72, SEM 0.06 to mean 1.57, SEM 0.06; Z=2.42; P=.03; psychosomatic problem: from mean 0.40, SEM 0.03 to mean 0.32, SEM 0.03; Z=2.66; P=.02; impulsivity-hyperactivity: from mean 0.94, SEM 0.06 to mean 0.80, SEM 0.06; Z=2.49; P=.03; hyperactivity index: from mean 1.06, SEM 0.05 to mean 0.92, SEM 0.05; Z=2.90; P=.01; n=97). No device-related adverse event or severe adverse event was observed or reported during or after the intervention. CONCLUSIONS This study preliminarily suggested the significant improvements of ADHD symptoms and attention function after 4 weeks of ADHD-DTx digital therapy combining basic behavioral parent training with satisfying safety outcomes.

Original Article Identification and validation of immunohistochemical marker panels to predict the prognosis of muscle invasive bladder cancer Yidie Ying, Ziwei Wang, Yuxin Tan, Haotian Cao, Hongliang Gao, Zhensheng Zhang, Shuxiong Zeng, Chuanliang Xu

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, with many gender differences, including attention dimensions. However, the gender differences in eye movements of different attention dimensions and the affecting factors in children with ADHD are still elusive. We enrolled 311 ADHD children who were initially diagnosed and used the combination of computer cancellation test and eye tracking (ET) to examined the eye movement patterns in different attention dimensions and its correlating factors and gender differences in ADHD children. We found that male ADHD children have more severe attention arousal deficits, and careless explorations of the target than females. There are significant gender differences in eye movement in children with ADHD, which are corelated to factors of attention dimensions and the executive function. Moreover, the integration of ET with attention cancellation tests produced a high AUC (1.000) value for identifying ADHD, and a high AUC (0.899) value for identifying ADHD genders. The results indicate that ET during cancellation tests can improve the identification of ADHD, and can effectively identify ADHD genders, which will help improve the clinical diagnosis and intervention of ADHD in different genders.

Fyn-related kinase (FRK) belonging to the Src family of non-receptor protein tyrosine kinases functions during the cell cycle. Here, we reported an autism spectrum disorders (ASD) patient with intragenic mutation of FRK with two other ASD risk genes. Circumventing the barrier of murine model studies, we generated the CRISPR/Cas9-engineered frk^−/− zebrafish. We found that frk-knockout led to increased brain sizes. Frk^−/− fish exhibited an ASD-like behavior, including impaired social communication, altered anxiety level, and cognitive dysfunction in both larvae and adults, which could be rescued by the transgenic neuron-specific re-expression of frk. GO and KEGG analysis of RNA-sequencing data found that the frk-knockout-induced DEGs were mainly concentrated in processes and functions related to cell metabolisms. PPI network analysis of the detected DEGs suggested that the cyp24a1/tp53 pathway may play a key role in frk-knockout-induced ASD. Furthermore, we found that the numbers of BrdU⁺ cells were significantly increased in the frk^−/− larval brains. Cyp24a1-inhibition or tp53-activation, reduced cell proliferation and partially ameliorated social impairments in frk^−/− zebrafish. Overall, our work established an ASD model of frk-knockout with assessable behavior phenotype in zebrafish and provided key insights into cell proliferation and the influence of cyp24a1/tp53 pathway-regulated cell proliferation on frk-knockout-induced ASD-like behaviors.

Bilirubin neurotoxicity is a serious consequence of hyperbilirubinemia, which is the most common disease of the neonatal period. Clinically, bilirubin neurotoxicity can result in motor deficit, auditory dysfunction, cerebral palsy, seizure and neurodevelopmental diseases, amongst others. Bilirubin neurotoxicity is one of the major worldwide causes of neonatal brain injury, especially in poorer developing countries. However, the mechanisms of bilirubin neurotoxicity are still unclear. After the failure of attempts targeting neurons in many neurodegenerative disorders, neuroinflammation has become a significant target of research. Here, recent advances concerning neuroinflammation in bilirubin neurotoxicity are reported with a focus on the clinical characteristics of bilirubin neurotoxicity, including age-dependency, region-specificity and its yin-yang properties. Effects of neuroinflammation on blood brain interfaces and treatments targeting neuroinflammation in bilirubin neurotoxicity are also reviewed, which may promote the precision of future treatment of bilirubin neurotoxicity.