Global developmental delay (GDD) affects 1–3% of young children, yet conventional rehabilitation is limited by accessibility, standardization, and individualization. Digital therapeutics (DTx) powered by artificial intelligence (AI) offer a scalable, adaptive alternative, but robust randomized evidence in GDD remains scarce. We assessed whether adding AI‑enabled DTx cognitive training to conventional rehabilitation improves developmental and adaptive outcomes in children aged 2–5 years with GDD. We conducted a multicenter, parallel‑group randomized controlled trial at five centers in China. We randomly assigned 118 children (1:1) to 16 weeks of either (i) conventional rehabilitation plus AI‑based digital cognitive training (intervention group, IG) or (ii) conventional rehabilitation plus an extra session of conventional cognitive‑language training (control group, CG). The primary outcome was change in developmental age (C‑PEP‑3). Secondary outcomes included adaptive functioning (S‑M scale) and developmental quotient (GDS). Intention‑to‑treat analysis used multiple imputation. Between‑group differences in change scores were compared with the Mann‑Whitney U test. The IG showed greater improvement in developmental age of C‑PEP‑3 (median difference 3.00 months, 95% CI 2.10 to 4.00; P<.001; r=0.505). Adaptive functioning (S‑M total score) also improved more in the IG (median difference 7.00 points, 95% CI 5.00 to 9.00; P<.001; r=0.582), as did GDS adaptive behavior (median difference 4.20 points, 95% CI 2.10 to 6.30; P<.001; r=0.373). Domain‑level gains favored IG across cognitive, social, and self‑help domains. Adverse events were mild and similar between groups. No serious adverse events occurred. AI-enabled DTx cognitive training improved cognitive and adaptive outcomes beyond those achieved with conventional rehabilitation alone. The intervention was safe and may provide a scalable adjunct for early intervention in children with GDD. Chinese Clinical Trial Registry: ChiCTR2500098770 （https://www.chictr.org.cn）

Importance Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited. Objectives To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention. Design, Setting, and Participants This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets. Main Outcomes and Measures The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale. Results The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment. Conclusions and Relevance In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.

Objective:To explore the regulatory effect of miR-873-5p micro-RNA targeting voltage-dependent anion channel protein 1 (VDAC1) in neurons and its mechanism.Methods:Murine nerve cells were randomly divided in vitro into a control group, a model group, a mimetic negative carrier (miR-con) group and an miR-873-5p group. The epileptiform hippocampal nerve cell model was induced in all of the cells except those in the control group using magnesium-free medium. The control group was normally cultured, while the miR-con and miR-873-5p groups were transfected with miR control and miR-873-5p RNA respectively. Real-time fluorescent quantitative polymerase chain reactions were used to detect the expression of miR-873-5p and VDAC1 mRNA. Western blotting was employed to detect VDAC1, B-cell lymphoma/leukemia-2 protein (Bcl-2), Bcl-2 associated X protein (Bax) and cleared caspase-3 in the neurons. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) were measured using the DCFH-DA fluorescent probe, the thiobarbituric acid method and enzyme-linked immunosorbent assay respectively. Any apoptosis was detected using flow cytometry, while the targeting of miR-873-5p on VDAC1 was verified using the double fluorescence zymase reporter gene method.Results:Compared with the control group, a significant decrease in the average expression of miR-873-5p, Bcl-2 and in GSH and MDA levels was observed in the model group, but there was a significant increase in the average level of VDAC1, Bax, cleaved caspase-3 and ROS and in the rate of apoptosis. Compared with the miR-con group, a significant decrease in the average expression of Bax, cleaved caspase-3, ROS and in the apoptosis rate was observed in the miR-873-5p group, but there was a significant increase in the average level of Bcl-2, GSH and MDA. Moreover, it was verified that miR-873-5p reduced the expression of VDAC1.Conclusion:miR-873-5p protects damaged neurons by inhibiting their apoptosis through negatively regulating the target gene VDAC1 and the oxidative stress response.

OBJECTIVES:To investigate the expression and mechanism of the long non-coding RNA (lncRNA) HCG22 in oral squamous cell carcinoma (OSCC). METHODS:HCG22 levels were detected in the OSCC and adjacent tissues, OSCC cells, and normal oral keratinocytes. HCG22 expression in SCC-25 and HSC-3 cells was upregulated by transfection of the overexpressing plasmi dvector. Methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, and Transwell assay were employed to detect changes in cell proliferation, apoptosis, migration, and invasion ability, while Western blotting was used to detect the expression of epithelial-mesenchymal transformation-related proteins. The expression level of miR-650 in the cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and dual-luciferase reporter gene assay was applied to assess the targeting relationship between HCG22 and miR-650. RESULTS:Compared with that in adjacent tissues, the expression of HCG22 significantly decreased in OSCC tissues (P<0.05). Moreover, the prognostic survival of patients in the low-HCG22 expression group was significantly lower than that in the high-expression group (P<0.05). Compared with that in HOK cells, the expression of HCG22 was significantly lower in SCC-25, HN13, HSC-3, and CAL-27 cells (P<0.05). Upregulation of HCG22 expression could inhibit the proliferation, migration, invasion, and apoptosis of SCC-25 and HSC-3 cells, upregulatethe expression of E-cadherin, and downregulate the expression of N-cadherin and vimentin (P<0.05). miR-650 mimics could reduce the luciferase activity of HCG22 wild-type plasmid cells (P<0.05), and the expression of miR-650 in SCC-25 and HSC-3 cells decreased after upregulation of HCG22 expression (P<0.05). CONCLUSIONS:HCG22 is expressed at low levels in OSCC. Upregulation of the expression of this lncRNA can inhibit the proliferation, migration, invasion, and epithelial-mesenchymal transition of OSCC cells. The mechanism of action of HCG22 may be related to its targeted regulation of miR-650.

目的:检测miR-126在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达,分析其表达与患者临床病理特征及预后的关系,探讨其过表达对Tca8113细胞恶性生物学行为的影响.方法:选取2016年6月至2018年6月在郑州大学第一附属医院手术治疗的62例OSCC患者的癌及癌旁组织标本,以及人舌鳞癌细胞株Tca8113和人口腔角质细胞株HOK,用qPCR法检测癌组织及细胞中miR-126的表达,分析miR-126表达与患者临床病理特征和预后的关系.利用脂质体转染技术,将miR-126 mimics、miR-NC质粒分别转染进Tca8113细胞,分别采用MTT法、流式细胞术及Trasnwell小室法检测细胞增殖、凋亡、迁移及侵袭能力,WB法检测凋亡、迁移和侵袭相关蛋白的表达水平.结果:miR-126在OSCC组织和Tca8113细胞中的表达水平明显低于癌旁组织和HOK细胞(均P＜0.01).miR-126表达与OSCC患者的TNM分期、淋巴结转移相关联(均P＜0.05),miR-126高表达患者的总生存率显著高于低表达组(P＜0.05).转染miR-126 mimics后,Tca8113细胞的增殖、迁移及侵袭能力明显降低(P＜0.05或P＜0.01),凋亡率明显升高(P＜0.01);细胞中Bcl-2、N-cadherin和vimentin表达水平明显降低(均P＜0.01),Bax和E-cadherin表达水平明显升高(均P＜0.01).结论:miR-126在OSCC组织及Tca8113细胞中低表达,上调miR-126可抑制Tca8113细胞的增殖、迁移和侵袭能力,并促进细胞凋亡.

目的 介绍河南省脑瘫儿童登记及康复管理平台(HCPRRMS)建设过程,探讨区域性脑瘫登记管理及监测网络建设思路.方法 系统性地介绍HCPRRMS建设过程、登记内容及初步结果.结果 2014年开始自主开发HCPRRMS,2015年3月开始登记单中心住院脑瘫儿童相关信息,2018年底开始在河南省多家县市级医疗及康复机构推广应用,截止到2019年9月共23家儿童康复机构使用.共纳入1357例脑瘫儿童,登记内容包括性别、出生体质量、孕周、高危因素、脑瘫分型、粗大运动功能分级(GMFCS)以及并发症情况.其中,男性936例(68.98％);孕周小于37周501例(36.92％);出生体质量小于2500 g 443例(32.65％);出生时并发缺氧缺血性脑病者430例(31.69％);脑瘫类型中痉挛型最多,为1117例(86.74％);不同型别脑瘫儿童GMFCS分级有显著性差异(P<0.05);有头部MRI检查记录者1117例,其中侧脑室周围白质软化为主的白质损伤最多,为480例(42.97％);并发症方面,并发癫痫196例(14.44％),并发视觉障碍109例(8.03％),并发听觉障碍158例(11.64％),≥2岁769例中,并发语言-言语障碍424例(52.66％),≥4岁216例中,并发智力障碍82例(37.96％).结论 HCPRRMS有助于了解脑瘫儿童高危因素、临床和影像学特点及并发症情况.

OBJECTIVE:To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP.METHODS:A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA.RESULTS:The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05).CONCLUSIONS:There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.

Objective:To observe the clinical efficacy and side effects of injecting different doses of botulinum toxin type A (BTX-A) into children with spastic cerebral palsy (CP) and tiptoe deformity.Methods:A total of 107 children with tiptoe deformity resulting from CP were divided into group A ( n=35), group B ( n=36) and group C ( n=36) using a random number table. Group A received 3u/kg injections of BTX-A, group B received 4u/kg injections and group C received 5u/kg. The injections were guided by color Doppler ultrasound and followed by 4 courses of rehabilitation therapy. Before and 1, 3 and 6 months after the treatment, the modified Tardieu scale (MTS) was used to assess gastrocnemius spasms, while sections D and E of gross motor function scale 88 (GMFM-88) and the pediatric balance scale (PBS) were used to evaluate motor functioning and balance. Any side effects were also observed. Results:After the treatment, improvement was observed in all of the measurements, though there were no significant differences in the degree of improvement nor in the incidence of side effects among the three groups.Conclusions:There is no significant difference in clinical efficacy or side effects involved in using different doses of BTX-A to treat tiptoe deformity in children with spastic cerebral palsy. The recommended dosage is therefore 3u/kg.

Objective To investigate the clinical effect of kinesitherapy combined with rTMS and BOTOX-A in the treatment of cerebral palsy. Method 94 cases with cerebral palsy were randomly divided into two groups, 47 cases in each group. The two groups were all given kinesitherapy, the observation group was plus rTMS and BOTOX-A on this basis. The course of treatment was 3 months, and the patients were followed up for l year. The clinical effect, MAS scores and GMFM-88 scores of the two groups were compared. ADL scores of the two groups before treatment and after 1 year follow up were compared. Results Total effective rate of the observation group (89.4％) was higher than that of the control group (70.2％)(P＜0.05). MAS scores of the two groups after treatment were significantly lower than those before treatment (P ＜ 0.01),GMFM-88 scores were significantly higher than those before treatment (P ＜0.01),the observation group changed more significantly than the control group (P＜0.01). After 1 year follow up, the ADL scores of the two groups were all significantly increased (P＜0.01),the observation group improved more significantly than the control group (P＜0.01). Conclusion The application of kinesitherapy combined with rTMS and BOTOX-A in the treatment of cerebral palsy has significant curative effect, it can significantly alleviated the muscle spasm degree of both lower limbs, and improve the motor function and activity of daily living.

目的 探究A型肉毒毒素(BTX-A)局部注射联合康复训练对痉挛型脑性瘫痪(CP)患儿下肢运动功能及生活质量的影响.方法 98例痉挛型CP患儿随机分组,各49例.对照组仅采取康复训练治疗,观察组联合BTX-A局部注射治疗,比较两组治疗前后肌肉痉挛程度、下肢运动功能及治疗后生活质量.结果 观察组治疗6个月后肌肉痉挛程度较对照组降低,走跑跳功能评分、生活质量评分较对照组升高(P＜0.05).结论 联合应用A型肉毒毒素局部注射与康复训练治疗痉挛型脑性瘫痪患儿可明显提高其下肢运动功能及生活质量.

Objective To explore the effects of family rehabilitation training (FRT) on gross motor function (GMF) and activity of daily living of children with cerebral palsy (CP). Methods Ninety-six CP children were assigned to observation (n=55) and control group (n=41) according to patriarch's treatment will. Both groups received routine rehabilitation training and observation group was plus FRT on the basis of routine rehabilitation training. GMFs were measured with the Gross Motor Function Measure-88 (GMFM-88) and activities of daily living assessed with the Activity of Daily Living Scale (ADL) before and after training. Results After treatment the GMFM-88 and ADL score heightened more significantly compared with pretreatment in observation group (P<0.01),had no notably changes in control group (P>0.05),and were significantly higher in observation than in control group (P<0.05 or 0.01). Conclusion Family rehabilitation training could effectively improve gross motor function and activity of daily living of children with CP and deserves generalization and application.

目的:总结位点药物注射方法治疗120例精神发育迟缓患者的临床经验.方法:将120例精神发育迟缓患者分为治疗组60例和对照组60例,治疗组在给予常规康复治疗的基础上,给予位点药物注射,对照组仅给予常规康复治疗,观察治疗效果.结果:经过治疗,两组患者智力水平均有提高,治疗组患者智力水平提高更显著,两组差异有统计学意义(P＜0.05).结论:精神发育迟缓患者在常规康复治疗的基础上同时给予位点药物注射,能够提高其智力水平,改善社会适应能力,提高日常生活能力及生存质量.

Objective To study the effect of Chinese herbal fumigation and steaming in the treatment of infantile spastic cerebral palsy . Methods 66 cases of infantile spastic cerebral palsy patients in our hospital from March 2013 to November 2015 were selected as research objects.And they were randomly divided into observation group and control group , and each group had 33 cases.The control group was treated with conventional therapy .The observation group was treated with traditional Chinese medicine fumigation and steaming therapy based on the control group .The therapeutic effect of the two groups was compared .Results The total effective rate of the observation group was 90.91%, the total effective rate of the control group was 66.67%, and the difference was statistically significant (P<0.05).Conclusion Chinese medicine fumigation and steaming in the treatment of infantile spastic cerebral palsy has significant effect and a certain clinical value, and it is worth promoting and applying .

目的 分析研究穴位注射治疗精神发育迟缓伴语言障碍患儿的治疗效果.方法 抽取我院接收的80例精神发育迟缓伴语言障碍患儿作为研究对象,随机分为观察组与对照组,各40例,对照组采用常规康复治疗及语言训练,观察组加用穴位注射治疗,对比两组患儿疗效及治疗前后语言发育商评分.结果 观察组治疗总有效率85.0％,远高于对照组的52.5％,差异显著(P＜0.05);治疗前两组Gesell语言DQ评分相比,无显著差异(P＞0.05);治疗后,观察组各项指标评分明显高于对照组,差异显著(P＜0.05).结论 在对精神发育迟缓伴语言障碍患儿进行常规康复治疗及语言训练基础上加用穴位注射治疗效果显著,可有效改善患儿语言发育商评分,提高治疗效果.

目的：探讨综合性康复疗法对精神发育迟滞（mental retardation，MR）患儿精神集中力及生活能力的影响。方法选取郑州大学第三附属医院2013年1月至2014年6月收治的50例精神发育迟滞患儿为研究对象，均接受综合性康复治疗，比较治疗前后患儿智力和生活能力情况。结果治疗后言语智商（VIQ）、操作智商（PIQ）及总智商（FIQ）明显高于治疗前，差异均有统计学意义（P ＜0.05）。治疗后日常生活能力量表（ADL）评分明显高于治疗前，差异有统计学意义（P ＜0.05）。结论综合性康复治疗能明显提高 MR 患儿智商和生活能力，值得临床推广。

目的：探讨综合康复治疗对脑瘫儿童神经功能及运动能力恢复的影响。方法将郑州大学第三附属医院收治的88例脑瘫患儿按抽签法随机分为观察组与对照组，各44例，分别采取综合康复治疗与基础治疗。比较两组患儿治疗前后Ashworth痉挛评定量表及综合功能变化。结果治疗后观察组患儿的Ashworth痉挛评定0级明显高于对照组，Ⅲ、Ⅳ级明显低于对照组；在认知能力、语言能力、运动能力、社会适应性、自理动作评分均较对照组明显提升，差异均有统计学意义（均P＜0.05）。结论综合康复治疗脑瘫儿童效果明显，可明显改善神经功能、运动功能等综合功能。