Compared to the general population, there is a higher prevalence of epilepsy in individuals with cerebral palsy (CP). Epilepsy serves as an indicator of CP severity and has a significant impact on the early survival and future quality of life of children with CP. Therefore, it is crucial to investigate the shared mechanisms underlying CP and epilepsy. This study aims to summarize the comorbidity of CP and epilepsy from genetic factors, risk factors, and pathophysiological mechanisms, in order to provide a reference for further research.

Objective To analyze the needs and current situation of home-based exercise rehabilitation for people with disabilities,develop service plans for different types of disabilities,and assess its health benefits for people with severe dis-abilities. Methods Based on the World Health Organization(WHO)Global Action Plan on Physical Activity 2018-2030:More Ac-tive People for a Healthier World and WHO Guidelines on Physical Activity and Sedentary Behavior,functional and individualized home-based exercise rehabilitation plans for people with severe disabilities were developed.Begining from May,2023,a six-month intervention was conducted for 37 people with severe disabilities.They were assessed with International Physical Activity Questionnaire(IPAQ),WHO Disability Assessment Schedule 2.0(WHODAS 2.0),WHO Quality of Life(WHOQOL-BREF)before and after intervention. Results The time of low-intensity leisure physical activity of IPAQ increased after intervention,while the scores of do-mains of cognition,mobility,self-care,getting along,life activities and participation,and total score of WHO-DAS 2.0 decreased,and the scores of physical health,psychological health,independence,and environment di-mensions,and total score of WHOQOL-BREF increased. Conclusion The functioning-oriented and individualized home exercise rehabilitation program can improve the level of physical activity,enhance the level of activity and boost the quality of life for people with severe disabilities.

AIM:This study utilized CRISPR/Cas9 technology to create Retnlb floxp knock-in mice,followed by the application of the Cre-LoxP recombination system to generate intestinal epithelial-specific Retnlb gene knockout mice(Retnlb-CKO).This model was developed to investigate the pathogenic mechanisms of Retnlb in inflammatory bowel disease.METHODS:Female and male C57BL/6N mice,aged 8 weeks with the Retnlbflox/+genotype,were housed togeth-er for breeding.Offsprings were screened to identify those with the Retnlbflox/flox genotype.These mice were then crossed with Vil1-Cre transgenic mice,which express Cre recombinase specifically in intestinal epithelial cells,resulting in Retnlb-flox/+,Cre+mice.Subsequent crosses between Retnlbflox/+,Cre+mice and Retnlbflox/flox mice produced Retnlbflox/flox,Cre+mice(Retnlb-CKO).Six 8-week-old Retnlbflox/flox,Cre+mice and their littermate Retnlbflox/flox mice were selected for experiments.RT-qPCR and immunohistochemistry were used to assess Retnlb mRNA and protein levels in colonic epithelium.Phenotypic observa-tions included body length,weight,diet,and reproductive capability.Tissue-to-body weight ratios were calculated to ana-lyze growth and development.Intestinal barrier integrity and colonic expression of inflammatory factors were evaluated.RESULTS:The conditional gene knockout mouse model with specific deletion of Retnlb in intestinal epithelial cells was successfully established and validated through genetic identification,mRNA and protein analysis.Compared to Retnlbflox/flox mice,Retnlb-CKO mice exhibited no significant differences in body length,weight,diet,or reproductive capability.There were no differences in the ratios of heart,liver,spleen,lung,kidney,and colon weight to body weight,nor were there morphological differences in various tissues.However,the mRNA expression of tight junction proteins ZO-1,Occlu-din,and Claudin3 in colon tissues of Retnlb-CKO mice was significantly reduced(P<0.01).PAS staining and immunohis-tochemistry revealed a significant decrease in the number of goblet cells and lysozyme-positive cells in the colon tissues of Retnlb-CKO mice(P<0.01).HE staining showed no obvious pathological change in colon tissues of Retnlb-CKO mice.RT-qPCR further demonstrated a significant downregulation of pro-inflammatory factors NLRP3,interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α)in colon tissues(P<0.01),along with significant downregulation of inflamma-tion signaling pathway proteins TLR4,MyD88,and NF-κB(P<0.01).CONCLUSION:A conditional colon epithelial cell Retnlb gene knockout mouse model was successfully constructed and validated.The absence of Retnlb in colon cells led to impaired intestinal barrier function,decreased mRNA expression of pro-inflammatory factors in colon tissue,and downregulation of mRNA expression of inflammatory pathway proteins TLR4,MyD88,and NF-κB.

Objective:To analyze the application effect of health education based on real-life experience in the rehabilitation nursing of elderly patients with femoral neck fractures.Methods:Using the convenient sampling method, a total of 116 elderly patients with femoral neck fractures admitted to the First Affiliated Hospital of Zhengzhou University from August 2022 to June 2023 were selected as the research objects. The patients were divided into the control group and the observation group using the random number table method, with 58 cases in each group. Patients in the control group received routine health education, while patients in the observation group received health education based on real-life experiences in addition to the control group. The knowledge, attitude and practice of femoral neck fractures, self-care ability and limb function of the two groups before and after intervention, as well as the treatment compliance of the two groups were compared.Results:After intervention, the score of knowledge, attitude and practice level of femoral neck fractures in two groups were higher than those before intervention, and the scores of all dimensions in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05). After intervention, scores of Exercise of Self-Care Agency (ESCA) and Harris hip joint function of patients in both groups were improved and the scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05). The cognitive score of functional training, compliance score of functional training and compliance score of discharge follow-up in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Health education based on real-life experiences can effectively improve the knowledge, attitude and practice level, self-care ability and treatment compliance of elderly patients with femoral neck fractures. It can effectively promote the recovery of limb function in patients and is worthy of clinical application.

Objective To investigate the best evidence application of exercise prescription in patients with chronic heart failure in clinical practice and evaluate its effectiveness.Methods The best evidence of exercise prescription for patients with chronic heart failure was summarized,and the evidence-based practice plan was developed,and it was implemented in the cardiology department of a tertiary hospital in Zhejiang Province from August to October,2022.Nurses'exercise prescription knowledge-attitude-practice level,implementation rate of review indicators,the length of hospital stay,exercise endurance,daily living ability and grip strength of both groups before and after the intervention were compared.Results After the application of the best evidence,the score of knowledge dimension was(9.34±0.98)points;the score of attitude dimension was(63.29±1.37)points;the score of practice dimension was(25.49±1.51)points,which were statistically significant compared with the scores before the application of evidence(P<0.05).After the application of the best evidence,the implementation rate of 16 review indicators was higher than that before the application of evidence(P<0.001).The length of hospital stay in the evidence application group was shorter than that in the baseline examination group(Z=-2.610,P<0.001).After intervention,the exercise endurance,daily living ability and grip strength of patients in the evidence application group were improved compared with the baseline review group,and the difference was statistically significant(P<0.05).Conclusion After the application of the best evidence of exercise prescription in patients with chronic heart failure,it can improve the level of knowledge,attitude and practice of nurses on exercise prescription,standardize the compliance of nurses'exercise prescription,reduce the number of days in the hospital,and improve patients'exercise endurance,daily living ability and grip strength.

Objective:To explore the short-term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costo-osteochondral autograft.Methods:From August 2022 to July 2023, 7 patients with open digit joint defects had undergone emergency primary debridement and fracture fixation in the Department of Orthopaedics, 988th Hospital of the Joint Logistics Support Force of PLA. Patients with more phalangeal defects that could not be aligned were treated with antibiotic bone cement filling in the emergency surgery. In the second stage surgery, bone cement was removed and transfer of rib cartilage graft was performed to reconstruct the digit joint defect. According to a 1∶1 3D printed hand templates, rib cartilage grafts were crafted to the shape of digit joints, and then spliced together the digit joints and bone defects for fixation. Follow-up X-ray examinations were taken and assessment of the healing status of rib and fractures of phalangeal and metacarpophalangeal bones were carried out according to the Paley fracture healing score. At the outpatient follow-up, assessment of transferred joint movement and evaluation of upper limb function were conducted according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Visual Analogue Scale (VAS) pain scores were evaluated from the affected digits and donor sites.Results:After reconstructive surgery, all 7 patients had primary healing of the wounds of hand. One patient had fat liquefaction at the donor site, and the rest had primary donor site healing. One patient received further surgery for extensor tendon repair after rib cartilage grafting due to the digital extensor tendon injury. All 7 patients were included in postoperative follow-up for 6-11 months, with an average of 9 months. All patients had excellent fracture healing according to the Paley fracture healing score. At the final follow-up, the extension and flexion of the digit joints were found at 40°-80° (average 56.2°) for proximal interphalangeal joints (4 patients), and 10° in extension and 85° in flexion for metacarpophalangeal joint (1 patient). The range of motion of the thumb interphalangeal joint (2 patients) was 20°-35° (average 27.5°). Hand function was assessed according to Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and it was found that 3 patients were in excellent, 3 in good and 1 in fair.Conclusion:This study focused on the treatment of traumatic digit joint defects by transfer of individually crafted rib cartilages in reconstruction of the defected digit joint. It significantly improves the appearance and function of the defected digit joints, especially suitable for the irregular defects of phalangeal bones.

ObjectiveTo construct a research framework for systematic review of health and functional outcomes of whole body vibration training in children and adolescents with cerebral palsy based on the theory and method of World Health Organization Family of International Health Classifications (WHO-FICs), and to systematically review the major health conditions and physical functions, intervention programs of whole body vibration training, and health and functional outcomes of vibration intervention in children and adolescents with cerebral palsy. MethodsBased on the WHO-FICs method, the PICO architecture of systematic reviews was constructed, and the databases of CNKI, Wanfang Data, PubMed, Web of Science, EBSCO, and Embase were searched to collect randomized controlled trials about the health and functional effects of whole body vibration training on children and adolescents with cerebral palsy from the establishment to September 30th, 2022, and a systematic review was conducted. ResultsEight articles, seven in English and one in Chinese, from five countries, were included, mainly from journals in clinical rehabilitation, neurorehabilitation, physical medicine and rehabilitation, etc., published mainly after 2010, involving 227 participants (three to 12.3 years old). The quality of the articles was evaluated using the Physical Therapy Evidence Database scale with a mean score of six. The ICD-11 codes included 08 diseases of the nervous system, 8D20 spastic cerebral palsy, 8D20.1 spastic bilateral cerebral palsy, 8D20.10 spastic quadriplegia cerebral palsy and 8D2Z unspecified cerebral palsy. The primary functioning of cerebral palsy was characterized as muscle spasticity, abnormal skeletal development, joint deformities and muscle weakness, decrease of selective motor control and gait abnormalities; for the activity and participation, the functioning included walking difficulties, decrease of mobility and weight loading, and low levels of physical activities. The main intervention was whole body vibration, in postures of lying, squatting or standing, mainly standing, in the mode of vertical vibration. The frequency was 5 to 30 Hz, and the amplitude was below 9 mm, three to five times a week for eight weeks to six months. The intervention settings include medical institutions, schools and families; mainly for therapeutics and recovery. The health and health-related outcomes were mainly involved s7 structures related to movement, b710 mobility of joint functions, b730 muscle power functions, b735 muscle tone functions, b760 control of voluntary movement functions, d410 changing basic body position, d415 maintaining a body position, d450 walking, d455 moving around, and d420 transferring oneself; such as improvements of neuromusculoskeletal and joint functions, muscle spasm, static balance, muscle strength, and control of movement, the control of body posture and walking, range of activities and self-care. ConclusionWhole body vibration training is effective on cerebral palsy, mainly in standing position, 5 to 30 Hz, and amplitude below 9 mm; three to five times a week for eight weeks to six months. The outcomes of whole body vibration training are mainly reflected in the improvement of body-motor functions, and activity and participation.

ObjectiveTo analyze the content and psychological measurement indicators of the commonly used motor function assessment tools for children and adolescents, based on the theory and method of International Classification of Function, Disability and Health-Children and Youth Version (ICF-CY). MethodsBased on the ICF-CY classification framework and coding system, four commonly used functional evaluation tools for children and adolescents were selected, and their motor function measurement methods and psychological measurement indicators were analyzed by applying ICF coding rules and matching principles. ResultsFinally, nine English articles and two Chinese articles were included, from four countries including South Korea, Spain, China and Brazil. They were mainly published in the journals of clinical medicine, neuroscience, public health, rehabilitation science and other fields from 2011 to 2021. The age of the subjects was 0 to 16 years old involving 987 subjects; the health condition included spastic cerebral palsy, neurodevelopmental disorder, etc. Among the eleven articles included, six articles used Gross Motor Function Measure (GMFM-88), two articles used Fine Motor Function Measure Scale (FMFM), two articles used Peabody Developmental Motor Scales Second Edition (PDMS-2), and two articles used Pediatric Evaluation of Disability Inventory-Functional Skills Scale (PEDI-FSS), and three articles used Pediatric Evaluation of Disability Inventory (PEDI). The measurement methods were objective evaluation, subjective evaluation, and subjective observation, etc. The number of measurements was two to six. The measurement indicators of motor function mainly involved two levels. The first was the physical activity level, including gross movement, fine movement and motor control ability. The second was the functional level of activities, mainly including activities of daily living and functional independence. ConclusionBased on ICF-CY, the evaluation of children's motor function and activity and participation was mainly divided into two levels. At the body function level, the main evaluation indicators included b730, b760, b770, etc. At the level of activities and participation, the main evaluation indicators were d410, d440, d445, etc. GMFM-88 focuses on the evaluation of children's body movement and activity functions, such as sitting, standing, lying, walking and running, mainly involving b760, d410, d455, etc. FMFM focused on autonomous movement, motor motivation and motor coordination, and was mainly used to assess the functional status of upper limbs of children with cerebral palsy aged 0 to 3 years, mainly involving b760, d155, d440, etc. PDMS-2 payed more attention to evaluating the overall motor development level and motor function status of children and adolescents, mainly involving b750, b760, d415, etc. PEDI-FSS move partition focused on children's actual motor function performance in activities of daily living, and evaluated the application and practicability of children's motor function in activities of daily living, mainly involving b760, d410, d450, etc. In terms of measurement methods, the measurement of motor function mainly included objective evaluation and subjective evaluation; the measurement of activity function mainly included objective evaluation and subjective observation. These assessment tools have established norms varies with different age groups according to the movement development. Evaluators need accept professional training before using the above assessment tools to improve the reliability, validity and adaptability of the assessment.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.