Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

Objective The aim of this study was to explore the natural history of Alzheimer's disease(AD)based on the multi-state Markov model and to provide methodological reference for the chronic diseases.Methods Based on the American public database ADNI,we constructed a three states Markov model to estimate the transition intensity,transition probability,influencing factors and sojourn time of different states.Survival curves and goodness of fit was obtained.Results Gender,age,FAQ,MMSE,CDRSB,ADAS13 and TMT-B-Time were important influencing factors in the natural history of AD.The mean sojourn time of NC and MCI was 7.502 and 11.621 years,respectively.Model fit can be accepted.Conclusion Multi-state Markov model has a good application value for the outcome prediction of multi-state chronic diseases such as AD.

Objective The shared random-effect model(SREM)was applied to study the reversion of mild cognitive impairment(MCI)to normal cognition(NC),to compare the predictive performance of different longitudinal cognitive markers for the reversion,and to evaluate the covariate effects of predictors.Methods The SREM model consisted of two sub-models:the longitudinal sub-model adopted linear mixed model to describe different longitudinal cognitive markers trajectories;and the survival sub-model used proportional risk model to fit the survival process.Goodness of fit was based on the log-likelihood value,and information criterion.AUC(area under the curve)was used to evaluate the predictive performance of different longitudinal cognitive markers,including MMSE,CDRSB,FAQ,ADAS11,ADAS13 and ADASQ4.Results There were 72(8.54%)of 843 patients with MCI reversed to NC at the end of follow-up.The log-likelihood value of the SREM model based on spline-PH-GH parameter distribution was the largest,and AIC and BIC were the smallest;the SREM model based on CDRSB score as longitudinal cognitive marker had the best fitting performance,with high AUC values at different times ranging from 0.797 to 0.852,and the lowest prediction error,ranging from 0.0427 to 0.0429.Age,gender,education level,marital status and APOEε4 gene affected the cognitive function and daily activity function.Six different longitudinal cognitive markers influenced the reversion.Conclusion CDR score was the best predictor of cognitive function and the reversion in MCI patients.Cognitive function and daily activity function can be used as dynamic monitoring indicators of MCI reversion.

Objective To explore the dynamics of carers'caregiving dilemmas during different stages of disease progression in patients with diabetic foot ulcers,and to provide a basis for giving precise intervention strategies.Methods Based on the theory of Timing It Right,the phenomenological study was adopted.A purposive sampling method was used to select carers of patients with diabetic foot ulcers who were hospitalised in the Wound Repair Unit of a tertiary hospital in Beijing from March 2023 to February 2024 to conduct semi-structured interviews,and the data were analysed using the Colaizzi 7-step analysis method.Results Combined with the theory of Timing It Right,5 stages of diabetic foot ulcer development were formed,and 5 themes were extracted(①diagnostic period:mixed emotions,facing the dilemma of being unable to do anything;②therapeutic period:lack of knowledge of the disease,and the difficulties of bedside care;③recovery period:contradictions of the desire for rapid healing and the lack of caregiving ability;④transition period:poor patient adherence,and the hope for professional support;⑤adaptation period:the accumulation of negative emotions,and the persistence of caregiving difficulties),and 12 sub-themes.Conclusion At different stages of disease development in patients with diabetic foot ulcers,the caregiving dilemma of caregivers changes dynamically,and healthcare professionals should provide professional,personalised,and high-quality professional support according to their caregiving experience and needs at different stages to improve their quality of care and promote patients'recovery.

Objective The joint latent class model(JLCM)was applied to study the reversion of mild cognitive impairment(MCI)to normal cognition(NC),providing a methodology reference for the longitudinal study of chronic diseases.Methods The JLCM model consisted of three sub-models:the latent class sub-model adopted multi-class logistic regression to estimate the latent classes;the longitudinal process sub-model adopted linear mixed model to describe the longitudinal cognitive measurement;and the survival process sub-model adopted proportional risk model to fit the cognitive process.Goodness of fit was based on information criterion,posterior classification,comparison between predicted value and observed value and conditional independence assumption.Results The MCI population was divided into two latent classes based on the JLCM model,including 783(92.88%)and 60(7.12%),respectively.The latent class sub-model showed that gender,marital status,APOE4 and FAQ had statistical significance for the determination of latent classes.The longitudinal process sub-model showed male(β=-0.685,95%CI:-1.144,-0.226),being single(β=0.743,95%CI:0.200,1.286),not carrying APOE4(β=-1.201,95%CI:-1.636,-0.766)and without functional impairment(β=-1.868,95%CI:-2.095,-1.641)had higher MMSE scores.The survival process sub-model showed that high education level(HR=1.264,95%CI:1.134,1.395),being single(HR=1.593,95%CI:1.286,1.899)and not carrying APOE4(HR=0.453,95%CI:0.043,0.862)were protective factors for reversion to NC in MCI patients.Conclusion JLCM model has good application value in the study of chronic diseases such as cognitive impairment.

Objective:To observe the effects of acupuncture on the expression of circRNA_011989 and circRNA_009775 in the hippocampal tissue of cerebral ischemia/reperfusion injury(CIRI)rats.Methods:CIRI model rats were prepared by the thread bolus method and treated by means of acupuncture(AC).The Garcia score was used to assess the neurological function.TTC staining was used to detect the volume ratio of cerebral infarction.The target prediction website was used to predict the miRNAs and corresponding mRNAs bound by circRNA_011989 and circRNA_009775,and Cytoscape was used to construct the circRNA-miRNA-mRNA co-expression network.The expression of circRNA_011989,circRNA_009775,miR-466b-5p,miR-3065-3p,Rims1,and Slc30a3 in the hippocampal region of the ische-mic side was detected by real time RT-PCR.Results:Compared with CIRI group,Garcia score of rats in CIRI+AC group was significantly increased(P＜0.01),and the infarct volume decreased.The expressions of circRNA_011989,circRNA_009775,Rims1,and Slc30a3 in right hippocampus were up-regulated(P＜0.05,P＜0.01),but the miR-466b-5p and miR-3065-3p were down-regulated(P＜0.05).Conclusion:Acupuncture may significantly ameliorate the neurological deficit symptoms in CIRI rats by upregulating the expression of circRNA_011989 and circRNA_009775,and the specific mechanism may be related to the activation of circRNA_011989/miR-466b-5p/Rim.s1 and circRNA_009775/miR-3065-3p/Slc30a3 axis related.

【Objective】 To investigate the transfusion ratio of plasma to RBC suspension during DIC caused by sever postpartum hemorrhage, so as to improve the clinical blood transfusion protocol. 【Methods】 A total of 82 parturients, who gave birth in our obstetrics department from January 2008 to December 2019 and treated successfully for DIC due to sever postpartum hemorrhage, were selected for the study. According to the plasma/RBC suspension ratio range (from 0.4 to 2.0) during DIC rescue, the included population was divided into four groups according to the ratio interval of 0.4: Group 1: 0.4~0.8 (13 people, median 0.7), Group 2 : 0.8~1.2(30 people, median 1.0), Group 3: 1.2~1.6(30 people, median 1.3), and Group 4: 1.6~2.0 (9 people, median 1.8). The general conditions, way of delivery, number of uterine artery perfusion embolization and surgical operations performed in the 4 groups were recorded. Once spontaneous postpartum hemorrhage occurred, blood cell analysis and coagulation function examinations were carried out every 1 to 2 hours until the condition was stable. The 24-hour blood loss, transfusion units of RBC suspension, fresh frozen plasma(FFP), platelet apheresis and fibrinogen during DIC and throughout the rescue of 4 groups were recorded and compared. Locally Weighted Regression (Lowess) method was applied to analyze the nonlinear association between the plasma/RBC suspension ratio and the duration of DIC, according to the duration of DIC in 4 groups. 【Results】 1) The shortest duration of DIC (326.15 min) was observed in DIC patients transfused with a plasma/ red blood cell suspension ratio=1.8. The duration of DIC (min) in the four groups were 505.21±259.53, 435.67±307.18, 420.93±259.43, and 247.86±215.77, respectively (P<0.05). 2) The coagulation indexes PT(s), INR, APTT(s) and Fib(g/L) gradually recovered between 2.9~13.9 h after transfusion in all four groups, especially in group 4 (median plasma/RBC suspension ratio of 1.8), whose changes were most pronounced in PT, INR, and Fib at 4.3 h, 2.9 h, and 5 h, respectively (P<0.05). 【Conclusion】 Fresh frozen plasma should be given as early as possible during blood transfusion treatment of DIC rescue. The increase of the ratio of plasma/RBC suspension is beneficial to the early recovery of DIC, and the optimal ratio of plasma to RBC suspension is 1.8.

Objective To study the clinical and genetic characteristics of congenital hyperinsulinism (CHI).Method From November 2016 to November 2018,a cohort of 21 patients with CHI were retrospectively reviewed in our hospital.The second generation sequencing was performed on Ion torrent platform to identify the genetic etiology of this disease.Result The average birth weight was 3 748 g.Overall,11 of the 21 patients (52.4％) were large for gestational age (＞ Pg0),and 90.5％ (19/21) onset within 3 days after birth.Seizures occurred in 7 cases (33.3％).Diazine was effective in alleviation in 6 patients,octreotide was effective in 8 patients,and diazine and octreotide were ineffective in 7 patients.11 patients underwent 18-fluoro-l-dopa PET-CT scan,indicating focal islet cell proliferation in 8 patients and diffuse islet cell proliferation in 3 patients.8 focal cases accepted the partial pancreatectomy (7 cases who failed to respond to drug therapy,1 case who received octreotide had significant liver damage),and all of these 8 cases were confirmed with focal islet cell proliferation by postoperative pathology.7 cases had normal glucose level after surgery,while 1 case developed insulin-dependent diabetes.Patients of 3 cases with diffuse islet cell proliferation had no consent for surgery.Gene mutations were identified in 61.9％ (13/21) of patients (12 cases of ABCC8 gene and 1 case of KCNJ11 gene).15 sequence changes were identified (14 in ABCC8 and 1 in KCNJ11).3 new ABCC8 gene mutations (exon13:c.1822C ＞ T,p.Q608X;exon22:c.2691delC,p.W898Gfs*5;exon33:c.4039C ＞T,p.Q1347X),and 1 new KCNJJ11 gene mutation (exon1:c.629T ＞ A,p.H315Y) were firstly reported.Conclusion Partial pancreatectomy is an effective treatment for those CHI not responsive to drug,however,with an attendant risk of developing diabetes.Mutations of ABCC8 gene and KCNJJ11 gene are the main pathogenic genes of CHI.Patients with different gene mutations may have different responses to drug treatment.Therefore,it is necessary to improve gene testing in clinical practice to guide treatment and prognosis.3 new ABCC8 gene mutations and 1 new KCNJJ11 gene mutation were first reported,which expand the spectra of gene mutation.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Objective To evaluate the levels of total serum bilirubin(TSB),amplitude integrated electroencephalogram(aEEG) monitoring and brainstem auditory evoked potential(BAEP) individually and in combination for the early diagnosis of neonatal acute bilirubin encephalopathy by receiver operating charac-teristic( ROC) curve. Methods Clinical data was retrospectively analyzed. A total of 152 infants were diag-nosed with hyperbilirubinemia,including 119 cases of non-bilirubin encephalopathy group and 33 cases of bil-irubin encephalopathy group. The detection results of peak serum bilirubin,aEEG,BAEP combined with the three methods were determined with ROC curve analysis. Results The areas under ROC curve of TSB lev-el,aEEG,BAEP and in combination were 0. 900,0. 738,0. 767,0. 925,respectively,the corresponding sensi-tivity(specificity) in the cut-off point were 90. 91%(78. 15%),87. 88%(59. 66%),65. 52%(87. 91%), 93. 10%(82. 42%),respectively. It showed that the area under ROC curve of the maximum,the comprehen-sive assessment in diagnostic sensitivity and specificity of the combination of three methods were better than any single detection method by ROC curve. Conclusion The methods of TSB level,aEEG and BAEP play an important role in the diagnosis of neonatal bilirubin encephalopathy,and combination with the three meth-ods can improve the accuracy of diagnosis.