AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

Objective:To explore the association between the gross motor development of children and Chi-nese developmental dyslexia.Methods:A total of 54 children were enrolled,indadit 27 children with Chinese DD and 27 age-gender-matched normal children.The Test of Gross Motor Development-Third Edition(TGMD-3),and the balance tests from the Movement Assessment Battery for Children(M-ABC)were used to evaluate the children's gross motor development level.Children's reading ability was evaluated by primary school students'literacy test question bank,one-minute reading task,and the Reading Test on Pupils.Results:The overall analysis of motortests showed that the grossmotor total score,locomotor score,object control score,and balance score in the DD group were significantly lower than those in the normal control group(P＜0.05).Logistic regression analysis revealed a negative association between balance scores,locomotor scores,object control scores,TGMD-3 total scores and indi-viduals with dyslexia(OR=3.08,1.35,1.16,1.13,Ps＜0.05).Conclusion:The delayed gross motor development of children is associated with the occurrence of Chinese developmental dyslexia.

AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

Objective:To explore the association between the gross motor development of children and Chi-nese developmental dyslexia.Methods:A total of 54 children were enrolled,indadit 27 children with Chinese DD and 27 age-gender-matched normal children.The Test of Gross Motor Development-Third Edition(TGMD-3),and the balance tests from the Movement Assessment Battery for Children(M-ABC)were used to evaluate the children's gross motor development level.Children's reading ability was evaluated by primary school students'literacy test question bank,one-minute reading task,and the Reading Test on Pupils.Results:The overall analysis of motortests showed that the grossmotor total score,locomotor score,object control score,and balance score in the DD group were significantly lower than those in the normal control group(P＜0.05).Logistic regression analysis revealed a negative association between balance scores,locomotor scores,object control scores,TGMD-3 total scores and indi-viduals with dyslexia(OR=3.08,1.35,1.16,1.13,Ps＜0.05).Conclusion:The delayed gross motor development of children is associated with the occurrence of Chinese developmental dyslexia.

Objective To explore the impact of exercise intervention on the reading abilities of chil-dren with Chinese developmental dyslexia(CDD).Methods Twenty-seven CDD children were recruited from patients of Peking University Sixth Hospital,and randomly divided into a CDD exercise interven-tion group of 14 and a CDD control group of 13.Another 14 age-matched normal children were select-ed into a normal control group.All groups kept daily physical activities in school,while the CDD ex-ercise intervention group additionally underwent 8-week individualized gross and fine motor interven-tion.The literacy,reading fluency and reading comprehension of all groups were evaluated by using"Elementary School Students'Literacy Test and Evaluation Scale",one-minute word reading and ele-mentary school students'reading ability assessment.Results Before the intervention,there were no sig-nificant differences between the exercise intervention and control groups in the literacy level,reading fluency,and reading comprehension(P>0.05),which were all significantly lower than the normal con-trol group(P<0.05).However,after the intervention,significant improvement was observed in the aver-age literacy level,reading fluency,and reading comprehension of the CDD exercise intervention group,and the literacy and reading fluency of the CDD control group,as well as the average literacy level and reading comprehension of the normal control group.Moreover,there were no significant differ-ences between the CDD exercise intervention and control groups in the average literacy level and read-ing fluency score(P>0.05),both significantly lower than the normal control group(P<0.05).Mean-while,the reading comprehension score of the CDD exercise intervention group was significantly higher than the CDD control group(P<0.05),but significantly lower than the normal control group(P<0.05).Conclusion Eight-week targeted gross and fine motor intervention can effectively improve reading abili-ty of DD children,especially their reading comprehension.

Objective:To summarize the best evidence for non-pharmacological interventions for postoperative pain in patients undergoing abdominal surgery, so as to provide reference for alleviating postoperative pain in patients.Methods:UpToDate, BMJ Best Practice, PubMed, Embase, Web of Science, Guidelines International Network and other databases and professional association websites were searched for guidelines, clinical decisions, evidence summaries, systematic reviews, expert consensus and randomized controlled trials on non-pharmacological interventions for postoperative pain in patients undergoing abdominal surgery. The search period was from the establishment of the databases to December 30, 2022.Results:A total of 17 articles were included, including three clinical decision-making, four guidelines, six systematic evaluations, two expert consensus, one randomized controlled trial and one quasi-randomized cotrolled trial. A total of 30 pieces of evidence were summarized from six aspects, such as basic principles of non-pharmacological intervention, evaluation and planning, physical intervention, psychological intervention, other forms of intervention, health education and follow-up.Conclusions:The best evidence for non-pharmacological intervention in postoperative pain in patients undergoing abdominal surgery can provide a basis for clinical medical staff to conduct non-pharmacological intervention.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

Objective: To investigate the relationship between fine motor skills and executive function in school aged boys with attention deficit hyperactivity disorder (ADHD) aged 6-10 years, so as to provide a reference for promoting executive function. Methods: From November 2022 to May 2021,65 boys with ADHD were recruited from a tertiary hospital in Beijing and a public elementary school in Beijing, and 65 boys with typical development according to age and sex were recruited as controls. Children s fine motor skills were assessed using the movement assessment battery for children, second version (MABC-2), and children s inhibitory control, working memory, and cognitive flexibility were assessed using the Stroop color word test (SCWT), Rey osterrich complex figure test (ROCFT) and trail making test (TMT), respectively. Independent samples t-tests were used to analyze the differences between the two groups, and Pearson correlation analysis and stratified regression analysis were used to explore the relationship between fine motor skills and executive functioning in boys with ADHD. Results: In the fine motor skills test, boys with ADHD scored significantly lower (8.68±3.62) than control boys (11.22±2.27)( t =4.80, P <0.05); in the executive function test, the results of SCWT, ROCFT, and TMT tests were significantly worse in boys with ADHD than in normal boys ( t =-4.53-4.42, P < 0.05). Correlation analysis showed that the fine motor skill scores of boys with ADHD were negatively correlated with the number of word sense errors ( r =-0.35) and color errors ( r =-0.42), and positively correlated with memory scores for delayed structure ( r =0.30) and detail ( r =0.25), which were negatively correlated with TMT-A ( r =-0.34),TMT-B reaction time ( r =-0.26), number of errors ( r =-0.43) ( P <0.05). Stratified regression analysis showed that fine motor skill scores of boys with ADHD were predictive of test results for inhibitory control, working memory and cognitive flexibility, with explanatory rates of 15%, 7%, and 19%, respectively. Conclusion Fine motor skills in boys with ADHD are correlated with executive functions, and fine motor skills could predict inhibitory control, working memory and cognitive flexibility to some extent. The development of fine motor skills in boy with ADHD could promote their executive functions.

Objective: To analyze epidemiological characteristics of campus bullying among primary and middle school students in central China to explore its relation with mental health problems, and to provide a reference for the campus bullying prevention. Methods: Stratified cluster sampling method was used to select primary and middle school 10 581 students from Anyang, Nanyang and Xinxiang cities of Henan Province, Middle School Students Mental Health Scale and the Self designed Scale of Adolescent Bullying Behavior were used to analyze the relationship between mental health problems with campus bullying behavior. Results: The total report rate of bullying penetrator was 12.5% among students in the three cities. Among primary and middle school students with mental health problems such as hostility, interpersonal stress, academic pressure and emotional imbalance, the detection rate of bullying behavior was 24.2%, 20.3%, 19.4% and 20.1%, respectively. The results of multivariate analysis showed that hostility symptoms ( OR =3.78, 95% CI =1.71-8.32), interpersonal stress ( OR =3.50, 95% CI = 1.62 -7.57), academic pressure ( OR = 1.62 , 95% CI =1.21-2.16) and emotional imbalance ( OR =2.80, 95% CI =1.41-5.56) showed a significant impact on campus bullying ( P <0.05). Conclusion Mental health problems of primary and middle school students are closely related to the occurrence of bullying behavior. It is necessary to pay attention to the mental health education of bullies and intervene bullying behaviors from the source.

Objective: To analyze the epidemiological characteristics of coronavirus disease 2019 (COVID-19) local infections in Zhejiang Province during the period between March and May, 2022, so as to provide the evidence for COVID-19 control. Methods: The individual investigation data and field epidemiological investigation data of local COVID-19 cases in Zhejiang Province from March to May 2022 were extracted from the National Diseases Prevention and Control Information System of China. The temporal, spatial and population distribution, identification and booster vaccination of local COVID-19 cases were analyzed using a descriptive epidemiological method. Factors affecting the severity of clinical symptoms were identified among local COVID-19 cases using a multivariable logistic regression model. Results: A total of 289 local COVID-19 epidemics occurred in Zhejiang Province from March to May 2022, and all infections were caused by the Omicron variant. A total of 1 598 local COVID-19 infections were reported, including 672 confirmed cases (42.05%) and 926 asymptomatic cases (57.95%), and the 672 confirmed case included 614 mild cases (91.37%), 58 normal cases (8.63%), while no severe, critically ill or dead cases were reported. The mean duration of COVID-zero community, mean duration of COVID-19 epidemics and mean length to COVID-19 peak calculated according to 7 epidemics with 50 and more cases were (6.14±1.07), (13.43±4.39), (3.00±1.63) d, respectively. COVID-19 infection was predominantly detected in centralized quarantine sites (1 105 cases, 69.15%), and 843 cases completed booster immunization of COVID-19 vaccines (52.75%). Multivariable logistic regression analysis showed that age (with ages of 60 years and older as the reference, age of 6 to 17 years, OR=0.111, 95%CI: 0.024-0.508; age of 18 to 44 years, OR=0.341, 95%CI: 0.163-0.713) and booster COVID-19 vaccination (OR=0.219, 95%CI: 0.117-0.410) were protective factors for developing more severe clinical symptoms following COVID-19 infections. Conclusions All local COVID-19 infections were caused by Omicron variant in Zhejiang Province during the period between March and May 2022, and all cases had mild clinical symptoms. Preschool children, middle-aged and elderly residents and individuals that did not complete booster COVID-19 vaccination may had relatively more severe clinical symptoms following COVID-19 infections.