Objective To clarify the concept of caregiver fatigue in an aging society and to provide references in the elderly people nursing.Methods Literature on caregiver fatigue was systematically retrieved from databases of China National Knowledge Infrastructure(CNKI),Wanfang Data,Chinese Biomedical Literature Database,PubMed,EMbase,Scopus,and Web of Science from the inception to June 15th 2024.Walker and Avant's framework for concept analysis was performed to analyse the retrieved literature.Results Forty-one papers were included in the study.Caregiver fatigue was identified to comprise of five defining attributes:simultaneous physical and psychological burden,subjective perception,changing over time,negative impact arising from caregiving,and negative impact on both caregivers and care recipients.Antecedents included three perspectives:caregiver-related,care-recipient-related and environmental,The consequences included an impact on both the caregiver and the person being cared for.Empirical assessment indicators of fatigue include the checklist individual strength(CIS)and the fatigue assessment instrument(FAI)and fatigue scale-14(FS-14,FS-14).Conclusion Walker and Avant's conceptual analysis identifies five attributes of caregiver fatigue.Nurses should pay attention to and evaluate the degree of caregiver fatigue from multiple perspectives,thereby effectively identifying and intervening in the fatigue as early as possible.

Objective:To investigate the neuroprotective effect of vanillin on experimental autoimmune encephalomyelitis(EAE)rats by regulating C-X-C motif chemokine ligand 12(CXCL12)/chemokine(C-X-C motif)receptor(CXCR4)signaling path-way.Methods:A total of 50 rats were injected with 400 μl guinea pig spinal cord and water in oil mixture of complete Freund's adju-vant to establish EAE rat model,and were divided into model group,low-dose vanillin group(50 mg/kg),medium-dose vanillin group(100 mg/kg),high-dose vanillin group(200 mg/kg)and positive drug group(5 mg/kg prednisone acetate),another 10 rats were only injected with the mixture of the same amount of normal saline and complete Freud adjuvant as control group,since the first day of mod-eling,all rats were given corresponding drugs by gavage for 16 consecutive days,and after modeling,rats in each group were scored for neurological function every day;HE and LFB staining were used to observe the pathology and demyelination of spinal cord in rats;levels of serum TNF-α,IL-1β and IL-6 were detected by ELISA;immunohistochemistry was used to detect expressions of CD68 and Iba-1 in spinal cord of rats;Western blot was used to detect expressions of CXCL12 and CXCR4 proteins in spinal cord of rats.Results:Compared with control group,rats in model group showed obvious infiltration of inflammatory cells,a large number of inflammatory cells gathered around the small blood vessels,and the structure of myelin sheath in spinal cord of rats was abnormal,accompanied by a large number of myelin sheath loss,the neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,spinal cord CD68 and Iba-1 proteins,CXCL12 and CXCR4 proteins expressions in-creased obviously(P<0.05);compared with model group,inflammatory cell infiltration and myelin sheath loss of rats in low,medium and high doses groups and positive drug group were obviously alleviated,neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,and expressions of CD68 and Iba-1 proteins in spinal cord decreased obviously(P<0.05),while expressions of CXCL12 and CXCR4 proteins in spinal cord further increased(P<0.05).Conclusion:Vanillin inhibits inflammatory response and alleviates nerve injury in EAE rats,and its mechanism may be related to acti-vation of CXCL12/CXCR4 signaling pathway.

Objective To explore the clinical value of mini-incision combined with balloon dilatation under the guidance of miniprobe echoendoscope in the treatment of refractory benign esophageal stenosis.Methods From October 2019 to October 2023,30 cases of esophageal early cancer with esophageal scar stenosis after endoscopic submucosal dissection(ESD)were selected and randomly divided into study group(miniprobe echoendoscope guided small incision+balloon dilatation,15 cases)and control group[esophageal radial incision(ERI),15 cases],EUS in the study group judged the hierarchical structure of esophageal wall before operation,and excluded those with esophageal cancer recurrence and submucosal invasive growth.According to miniprobe echoendoscope,the length of scar segment and the scope of scar ring lumen were defined,and the location and length of pre-incision were defined,and then balloon was used to expand step by step.The short-term postoperative complications,Stooler dysphagia scale score and restenosis rate of the two groups were observed,and the feasibility,safety and efficacy were evaluated.Results The incidence of short-term postoperative complications 6.7％in the study group was significantly lower than that 46.7％in the control group,the difference was statistically significant(P＜0.05),and the Stooler dysphagia scale score were(1.133±0.990)and(1.600±0.737)in the study group at 1 and 2 months after operation with significantly lower than those(2.067±1.033)and(2.467±0.915)in the control group,the differences were statistically significant(P＜0.05).Two months after operation,the restenosis rate was 13.3％,which was significantly lower than that 46.7％of the control group,the difference was statistically significant(P＜0.05),and the scar thickness under miniprobe echoendoscope(2.113±0.887)mm was significantly thinner than that(3.353±1.468)mm of the control group,the difference was statistically significant(P＜0.05).Conclusion Preoperative miniprobe echoendoscope evaluation,can accurately locate lesions,endoscopic mini-incision combined with balloon mechanical expansion are safe and effective,with less pain and fewer postoperative complication.

Objective:To investigate the neuroprotective effect of vanillin on experimental autoimmune encephalomyelitis(EAE)rats by regulating C-X-C motif chemokine ligand 12(CXCL12)/chemokine(C-X-C motif)receptor(CXCR4)signaling path-way.Methods:A total of 50 rats were injected with 400 μl guinea pig spinal cord and water in oil mixture of complete Freund's adju-vant to establish EAE rat model,and were divided into model group,low-dose vanillin group(50 mg/kg),medium-dose vanillin group(100 mg/kg),high-dose vanillin group(200 mg/kg)and positive drug group(5 mg/kg prednisone acetate),another 10 rats were only injected with the mixture of the same amount of normal saline and complete Freud adjuvant as control group,since the first day of mod-eling,all rats were given corresponding drugs by gavage for 16 consecutive days,and after modeling,rats in each group were scored for neurological function every day;HE and LFB staining were used to observe the pathology and demyelination of spinal cord in rats;levels of serum TNF-α,IL-1β and IL-6 were detected by ELISA;immunohistochemistry was used to detect expressions of CD68 and Iba-1 in spinal cord of rats;Western blot was used to detect expressions of CXCL12 and CXCR4 proteins in spinal cord of rats.Results:Compared with control group,rats in model group showed obvious infiltration of inflammatory cells,a large number of inflammatory cells gathered around the small blood vessels,and the structure of myelin sheath in spinal cord of rats was abnormal,accompanied by a large number of myelin sheath loss,the neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,spinal cord CD68 and Iba-1 proteins,CXCL12 and CXCR4 proteins expressions in-creased obviously(P<0.05);compared with model group,inflammatory cell infiltration and myelin sheath loss of rats in low,medium and high doses groups and positive drug group were obviously alleviated,neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,and expressions of CD68 and Iba-1 proteins in spinal cord decreased obviously(P<0.05),while expressions of CXCL12 and CXCR4 proteins in spinal cord further increased(P<0.05).Conclusion:Vanillin inhibits inflammatory response and alleviates nerve injury in EAE rats,and its mechanism may be related to acti-vation of CXCL12/CXCR4 signaling pathway.

Objective To explore the clinical value of mini-incision combined with balloon dilatation under the guidance of miniprobe echoendoscope in the treatment of refractory benign esophageal stenosis.Methods From October 2019 to October 2023,30 cases of esophageal early cancer with esophageal scar stenosis after endoscopic submucosal dissection(ESD)were selected and randomly divided into study group(miniprobe echoendoscope guided small incision+balloon dilatation,15 cases)and control group[esophageal radial incision(ERI),15 cases],EUS in the study group judged the hierarchical structure of esophageal wall before operation,and excluded those with esophageal cancer recurrence and submucosal invasive growth.According to miniprobe echoendoscope,the length of scar segment and the scope of scar ring lumen were defined,and the location and length of pre-incision were defined,and then balloon was used to expand step by step.The short-term postoperative complications,Stooler dysphagia scale score and restenosis rate of the two groups were observed,and the feasibility,safety and efficacy were evaluated.Results The incidence of short-term postoperative complications 6.7％in the study group was significantly lower than that 46.7％in the control group,the difference was statistically significant(P＜0.05),and the Stooler dysphagia scale score were(1.133±0.990)and(1.600±0.737)in the study group at 1 and 2 months after operation with significantly lower than those(2.067±1.033)and(2.467±0.915)in the control group,the differences were statistically significant(P＜0.05).Two months after operation,the restenosis rate was 13.3％,which was significantly lower than that 46.7％of the control group,the difference was statistically significant(P＜0.05),and the scar thickness under miniprobe echoendoscope(2.113±0.887)mm was significantly thinner than that(3.353±1.468)mm of the control group,the difference was statistically significant(P＜0.05).Conclusion Preoperative miniprobe echoendoscope evaluation,can accurately locate lesions,endoscopic mini-incision combined with balloon mechanical expansion are safe and effective,with less pain and fewer postoperative complication.

Objective To investigate the differences of language abilities between children with developmental delay(DD)and those with autism spectrum disorder(ASD)aged 3-6 years,and to provide references for clinical differential diagnosis and subsequent rehabilitation therapy.Methods In this study,61 cases of DD children and 61 cases of ASD chil-dren were selected.The language ability of children was assessed using the"Children's Language Ability Assessment Stand-ards and Methods",which evaluated grammar,comprehension,expression and communication abilities.Results Children with DD showed better comprehension and social skills but weaker grammar and expressive abilities.Children with ASD generally had lower levels in all language areas.There was no significant difference in the average language ability or expres-sive ability the two groups(P＞0.05),but the language comprehension ability and communication ability of the ASD group were significantly lower than those of the DD group(P＜0.05).The grammar ability of the ASD group was higher than that of the DD group(P＜0.05).Conclusion The levels of different language areas of children with DD and ASD children are significantly different.Language ability tests can assist in the differential diagnosis of DD and ASD children,and provide reference for language rehabilitation training.

Objective:To investigate the role of hypoxia-induced angiopoietin-like protein 4 (ANGPTL4) expression in experimental choroidal neovascularization (CNV).Methods:Twenty-seven SPF male C57BL/6J mice aged 6-8 weeks were selected.Eighteen of the mice were used to establish a laser-induced CNV model.On the 7th day after laser photocoagulation, success of the modeling was verified using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA). The retinal pigment epithelium (RPE)-choroid-sclera complex was extracted for protein analysis before modeling and on the 3rd and 7th days after modeling.The relative expression levels of ANGPTL4 and vascular endothelial growth factor (VEGF) at different time points were detected by Western blot.Additionally, frozen sections of mouse eyeballs on day 7 after modeling were prepared and the expression and cellular localization of ANGPTL4 were observed by immunofluorescence.RF/6A cells, derived from monkey choroidal retinal endothelial cells, were treated with 200 μmol/L cobalt chloride (CoCl 2) in the culture medium for 0, 3, 6, and 12 hours.RF/6A cells were also divided into a normal control group, a hypoxia group, and a hypoxia+ si-ANGPTL4 group, and cells were transfected with a plasmid containing si-ANGPTL4 sequence.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot, and the differences in tube formation among the groups were observed by tube formation assay.A total of 27 male C57BL/6J mice were randomly divided into CNV group, CNV+ si-NC group, and CNV+ si-ANGPTL4 group, with 9 mice in each group.In the CNV+ si-NC and CNV+ si-ANGPTL4 groups, si-NC and si-ANGPTL4 were respectively injected into the vitreous cavity after the CNV model was established.Fluorescence leakage in mice was observed by FFA, and the length, thickness and area of CNV was observed using OCTA and immunofluorescence staining of choroidal flat mounts.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot.All animal experiments were conducted in accordance with ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.The experimental protocol was approved by the Affiliated Hospital of Nantong University (No.S20220822-902). Results:Before modeling and on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 protein were 1.00±0.00, 1.58±0.05, and 1.90±0.04, respectively, and the relative expression levels of VEGF protein were 1.00±0.00, 1.31±0.05, and 1.84±0.04, respectively, with statistically significant overall differences ( F=528.934, 390.424, both P<0.05). Among them, on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 and VEGF proteins were significantly higher in CNV group than in the control group (all P<0.05). The tissues of each layer of the retina were clear in the control group, while neovascularization could be seen growing under the retinal neuroepithelial layer in the CNV group.Compared with the control group, ANGPTL4 expression was significantly increased and colocalized with vascular endothelial cells in the CNV group.After CoCl 2 treatment of RF/6A cells for 3, 6, and 12 hours, the relative expression levels of ANGPTL4 and VEGF proteins were higher than at 0 hour, with statistically significant differences (all P<0.05). Compared with the control group, the relative ANGPTL4 protein expression was increased in the hypoxia group and significantly decreased in the hypoxia+ si-ANGPTL4 group, showing statistically significant differences (both P<0.05). The number of tube formations in the control group, hypoxia group, and hypoxia+ si-ANGPTL4 group were 12.67±1.53, 19.64±1.56, and 17.01±1.04, respectively, with a statistically significant overall difference ( F=33.091, P<0.01). The number of tube formations increased in the hypoxia group and hypoxia+ si-ANGPTL4 group compared with the control group, and the number of tube formations decreased in the hypoxia+ si-ANGPTL4 group compared with the hypoxia group, with statistically significant differences (all P<0.05). Relative expression levels of ANGPTL4 and VEGF proteins were significantly lower in the CNV+ si-ANGPTL4 group than those in the CNV group (both P<0.05). The CNV area was significantly lower in the CNV+ si-ANGPTL4 group than in the CNV group and CNV+ si-NC group (both P<0.05). Conclusions:Hypoxia-induced ANGPTL4 promotes experimental CNV formation in vivo and in vitro.Inhibiting ANGPTL4 can reduce CNV formation and leakage.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.