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 explore the expression of checkpoint kinase 2 (CHEK2) in clear cell renal cell carcinoma (ccRCC), its association with the clinicopathological features and prognosis, and to predict its relevant molecular signaling pathways and biological functions. 【Methods】 The gene expression data, phenotype data, and corresponding survival information of ccRCC patients were downloaded from TCGA database. The optimal cutoff value of CHEK2 was determined with the "survminer" package. The patients were divided into low and high expression groups, and the association between CHEK2 expression and clinicopathological features was analyzed. The correlation between CHEK2 expression and ccRCC prognosis was evaluated with univariate and multivariate Cox proportional hazard models. The changes of cell signaling pathways involved in different CHEK2 expression levels were explored with gene set variation analysis (GSVA). The correlation between CHEK2 and immune cell infiltration as well as immune checkpoint molecular expression was analyzed. 【Results】 CHEK2 expression was significantly higher in ccRCC tissues than in normal tissues (P<0.01). Higher level of CHEK2 was significantly associated with higher T stage of ccRCC (P<0.01). Kaplan-Meier analysis showed overall survival (OS) of patients with high CHEK2 expression were notably decreased (P<0.001). Univariate and multivariate analyses revealed CHEK2 expression as an independent risk factor of survival (HR=1.950, 95%CI: 1.490-2.570, P<0.001; HR=1.588, 95%CI: 1.185-2.127, P=0.002). GSVA showed that CHEK2 was involved in the following pathways: proximal tubule bicarbonate reclamation, propanoate metabolism, limonene and pinene degradation, fatty acid metabolism, primary immunodeficiency, systemic lupus erythematosus, p53 signaling pathway, homologous recombination, DNA replication and mismatch repair. Correlation analysis suggested that CHEK2 was associated with increased infiltration of multiple immune cells in ccRCC and upregulation of various immune checkpoint molecules. 【Conclusion】 The high level of CHEK2 in ccRCC is an independent predicting factor for poor prognosis. It is probably involved in regulating related events of tumor immune infiltration and may become a new target for ccRCC therapy.

Objective To observe the electromyography characteristics of children's handwriting with attention deficit hyperactivity disorder(ADHD),and explore its electrophysiological mechanism,so as to provide an objective basis for developing non-pharmacological treatment for such children.Methods Between September 2021 and April 2022,29 ADHD children were recruited from an ordinary public primary school and the psychiatric clinic of a class-3 grade-A hospital in Beijing.Among them,25 were boys and 4 were girls,with an average age of 8.21±1.78 years.Meanwhile,23 male and 5 fe-male healthy counterparts were selected with the age gap no more than 6 months.The Delsys wireless surface EMG system was used to collect the electromyographic signals of the abductor pollicis breve,the first dorsal interosseous muscle,the flexor radial carpi motor and the extensor finger muscles dur-ing their writing tasks such as tracing trajectories,writing Arabic numerals 0-9,26 small and capital English letters,Chinese characters one to ten and"Yong".The percentage of the averaged electromyog-raphy(AEMG)of a muscle in the sum value of all measured muscles,and the coefficient of differ-ence were selected to evaluate the muscle contribution rate and the consistency of exertion,respective-ly.Moreover,the independent sample t-test was employed to compare the two different groups with the significance set at α=0.05.Results There was a significant difference in the muscle contribution of abductor pollicis breve and first dorsal interosseous muscles when writing Arabic numerals and that of abductor pollicis breve muscles when writing Chinese characters between ADHD children(27.29%,25.58%and 27.53%)and their healthy counterparts(42.87%,19.96%and 37.13%)(P<0.05).Most muscle differentiation coefficients of ADHD children were higher than 100%,with that of the domi-nant hand radial wrist flexor muscle reaching 270%in the trajectory tracing task.Conclusion Accord-ing to the characteristics of EMG signals,school-age ADHD children show an immature writing pat-tern,including poor stability of writing-related muscles,insufficient control of small finger muscle groups,poor control of hand coordination,and insufficient muscle inhibition of non-dominant hand.It is recommended to conduct the electromyoelectric assessment of handwriting movements in ADHD chil-dren,so as to carry out targeted intervention at an early stage.

Objectives:To investigate the relationships between CYP2C9 and VKORC1 polymorphism and the steady-state dose of warfarin in Chinese Han patients with nonvalvular atrial fibrillation.Methods:A total 544 Chinese Han patients with atrial fibrillation who received warfarin anticoagulant therapy in Department of Cardiology of Beijing Hospital, Tongren Hospital, Xuanwu Hospital, Anzhen Hospital and Tiantan Hospital were enrolled from January 2016 to may 2019. The genotype and allele frequency in exon 1, 2, 3, 7 of CYP2C9 gene and 1639 site of VKORC1 gene were analyzed; and the general information, warfarin steady-state dose and concomitant medication of patients were recorded.Results:There were four genotypes CYP2C9:CYP2C9*1*1 (93.57%, 509/544), CYP2C9*1 *2 (0.18%, 1/544), CYP2C9*1 *3 (5.88%, 32/544) and CYP2C9*1 *60 (0.37%, 2/544); while VKORC1 had three genotypes: AA (82.72%, 450/544), GA (15.99%, 87/544) and GG (1.29%, 7/544). After reaching the anticoagulation index (INR 2.0-3.0), the steady-state dose of warfarin was the highest in patients with CYP2C9 *1/*1 and VKORC1 GA/GG genotypes, reaching (3.70±1.34) mg/d. The lowest steady-state dose of warfarin was (2.17±0.29)mg/d in patients with both new mutations ( F=22.09, P<0.001). Multiple linear regression analysis showed that body surface area, use of amiodarone, CYP2C9 and VKORC1 genotypes were the independent influencing factors of warfarin steady-state dose ( t=4.44, -2.90, -6.96, 2.14; P<0.05) and the steady-state dose prediction model of warfarin was established. Conclusion:Body weight, height, body surface area, gender, smoking, and combination of amiodarone may significantly affect the steady-state dose of warfarin in patients. CYP2C9 and VKORC1 mutant genotypes were significantly related to the steady-state dose of warfarin. The prediction model based on genetic factors and other influencing factors may effectively predict the steady-state dose of warfarin in Han patients with atrial fibrillation.

Background: Previous studies showed controversial findings for correlation of periodontal disease and cognitive deficits. Methods: We searched systematically for studies pertaining to correlation of periodontal disease and cognitive deficits published between August 1980 and December 2019 on Web of Science and PubMed. We combined the data extracted from the included studies to determine the correlation between periodontal disease and cognitive deficits. Results: Our analysis indicated a higher risk of cognitive deficits in those with moderate to severe periodontal disease when compared to those with mild or no periodontal disease (odds ratio (OR) = 1.38 (95% confidence intervals (CI): 1.28-1.48). Subgroup analysis showed significant correlations in only case-control and cohort studies (case-control studies: OR = 1.49 (95% CI: 1.24-1.80); cohort studies: relative risk (RR) = 1.33 (95% CI: 1.22-1.45)). Subgroup analysis also indicated that moderate to severe periodontal disease was correlated to increased dementia and Alzheimer disease risks, whereas no significant correlation was found between periodontal disease and mild cognitive impairment (dementia: OR/RRs = 1.32 (95% CI: 1.22-1.44); Alzheimer disease: OR/RRs = 1.51 (95% CI: 1.20-1.90); Mild cognitive impairment: OR/RRs = 1.31 (95% CI: 0.89-1.94)). Furthermore, subgroup analysis showed significant correlations between cognitive deficits and tooth loss, periodontitis, whereas no significant correlation was found between deep periodontal pockets and cognitive deficits (tooth loss: OR/RRs = 1.57 (95% CI: 1.39- 1.77); periodontitis: OR/RRs = 1.43 (95% CI: 1.03-2.00); deep periodontal pockets: OR/RRs = 1.24 (95% CI: 0.77-2.00)). Conclusions: This review suggests a significant correlation between periodontal disease and cognitive deficits. Interventional studies for periodontal disease may be beneficial for patients with cognitive deficits

Objective:To verify the accuracy of the International Warfarin Pharmacogenetics Consortium(IWPC)model, identify the effects of genetic and clinical factors on steady-state doses of Warfarin, and establish a Warfarin dose prediction model for the Han-Chinese population aged 75 years and over under the guidance of pharmacogenetics.Methods:A total of 544 Han-Chinese patients receiving Warfarin therapy for atrial fibrillation were divided into two groups: those aged 75 years and over(n=164)and those aged below 75 years(n=380). Data for the whole population and the two age groups were each substituted into the IWPC prediction model for accuracy verification.Demographic and clinical characteristics of 164 patients aged 75 years and over were recorded, and the genotypes of CYP2 C9 and VKORC1- G1639 A were detected by polymerase chain reaction.A new pharmacogenetic-guided dosing algorithm for the elderly was obtained by stepwise multiple linear regression.The accuracy of the new model was compared with that of the IWPC model. Results:The predictive accuracy of IWPC for steady-state dosing of warfarin was 35.47% in all subjects, 33.75% in 164 subjects aged below 75 years, and only 28.70% in subjects aged 75 years and over, respectively.In 164 subjects aged 75 years and over, three genotypes of *1/*1, *1/*3 and *1/*2 were detected in CYP2 C9 polymorphism, and the CYP2 C9*1/*1 genotype was the most common one, with a frequency of 87.80%(144/164), followed by the CYP2 C9*1/*3 genotype, at 11.59%(19/164). GG, GA and AA genotypes were detected in VKORC1 polymorphism, among which the AA genotype accounted for 82.32%(135/164)and the GG genotype accounted for only 1.83%(3/164). The steady state dose for Warfarin in patients with the wild-type CYP2 C9*1/*1 was higher than in those with the heterozygote CYP2 C9*1/*3 and *1/*2(3.18±0.86 mg/d vs.2.27±0.51 mg/d, t=5.637, P<0.05). Patients with a mutant homozygotic AA genotype of VKORC1 required lower maintenance doses than those with the heterozygotic GA and GG genotypes(2.96±0.66 mg/d vs. 3.59±1.43 mg/d, t=-2.092, P<0.05). The steady-state dose for Warfarin in subjects carrying CYP2 C9 (*1/*2 or *3)and VKORC1 (GA and GG)was(2.00±0.63)mg/d, lower than in those carrying other genotype combinations( P<0.05). We established a new Warfarin dosing algorithm for elderly subjects aged 75 years and over containing height, creatinine, amiodarone usage, CYP2 C9 and VKORC1 mutants, and the accuracy of the new model was 56.0%, which could explain 56.0% of individual variability, and the accuracy was higher than that of the IWPC algorithm(56.0% vs. 45.8%, P<0.05). Conclusions:Polymorphisms of CYP2 C9 and VKORC1 clearly affect the steady-state dose for Warfarin in the elderly Han-Chinese population aged 75 years and over.A combination of pharmacogenomics with clinical factors can better guide warfarin medication in Han-Chinese people aged 75 years and over.

Objective:To investigate the differential expression of miRNAs during white adipose tissue(WAT)browning in mice under different stimulation conditions, and to analyze the potential regulatory mechanisms.Methods:Mouse models of subcutaneous WAT(sWAT)browning were established by different methods: cold-induced browning and intraperitoneal injection of CL316-243.HE staining and analysis of thermogenesis-related gene expression were used to validate the browning models.miRNAs expression profiles in different conditions were described by RNA-sequencing(RNA-seq)and miRNAs with similar expression patterns in the two groups were detected via screening.Target genes of miRNAs were predicted by bioinformatics, and their expression levels were verified by quantitative real-time PCR(qRT-PCR).Results:Both cold-induced browning and intraperitoneal injection of CL316-243 were able to activate the browning of sWAT, and the miRNA expression profile of sWAT showed significant differences before and after induction.After screening differentially expressed miRNAs, the expression of Mir-30E-3p was increased and the expression of Mir-181A-5p was decreased under different browning-inducing conditions in WAT.The prediction and validation of target genes revealed that cyclin-dependent kinase 6(Cdk6)and sirtuin 1(Sirt1)were potential targets regulated by miR-30e-3p and miR-181a-5p in the browning of sWAT, respectively.Conclusions:There are significant differences in miRNA expression during the browning of sWAT in mice induced by cold stimulation and CL316-243 injection.MiR-30e-3p and miR-181a-5p may be involved in the regulation of the sWAT browning process through target genes Cdk6 and Sirt1, respectively.

Objective: To explore the effect of hypoxia inducible factor 1α (HIF-1α) gene silencing in rat bone marrow mesenchymal stem cells (BMMSCs) under mechanical distraction on the expression of bone sialoprotein (BSP) and osterix and to provide a new idea for repairing bone defects with BMMSCs. Methods : The shRNA sequence was designed according to the rat HIF-1α gene, and the pGMLV-SC1RNAi lentiviral vector was cloned after PCR amplification. After screening positive clones and identifying competent transformed cells by sequencing, 293T cells were packaged and titered, rat BMMSCs were transfected and cultured in vitro. Clones with stably silenced HIF-1α expression were screened by inverted fluorescence microscopy. The RNAi response experiment was divided into four groups: the blank control group, the HIF-1α shRNA group, the negative control group, and the response group. Western blot was used to detect the expression of HIF-1α protein in the four groups to verify the response of the target genes and exclude off-target effects. A Flexcell FX-5000T cell stress loading system was used to intervene in the mechanical stretch of the cells. qRT-PCR and Western blot were used to detect the expression of BSP and osterix in the blank control group, HIF-1α shRNA group, and negative control group. Results: The HIF-1α shRNA lentiviral vector was successfully constructed. The results of the RNAi response showed no significant difference in the expression of HIF-1α between the response and the blank control group (P > 0.05). The recombinant lentivirus could effectively silence HIF-1α in BMMSCs. After mechanical distraction of the BMMSCs, compared with the blank and negative control groups, the HIF-1α shRNA group showed significantly increased mRNA and protein expression of the bone-related factors BSP and osterix (P < 0.05); there was no significant difference in the mRNA and protein expression of BSP or osterix between the blank and negative control groups (P > 0.05). Conclusion Silencing HIF-1α in BMMSCs under mechanical distraction can promote the expression of BSP and osterix.

OBJECTIVEThis study aimed to investigate the mechanism of cyclic stretch that promotesthe osteogenic differentiation of human periodontal ligament cells (hPDLCs) through the mediation of extracellular-signal-regulated kinase 1/2 (ERK1/2).

METHODShPDLCs were isolated through the explant method and cultured in vitro. hPDLCs were mechanically stimulated by a multi-channel cell-stress-loading system for 1, 3, 6, 12, and 24 h. The magnitude of stretch was 10% deformation, and the frequency was 0.5 Hz. Nonloaded cells were used as control group. ERK1/2 activation was blocked by U0126, a specific ERK1/2 pathway inhibitor. Additionally, hPDLCs were transfected with adenoviral vector encoding dominant negative ERK1/2 (DN-ERK1/2) to continuouslyinhibit ERK1/2 activation. The mRNA and protein levels of target geneswere detected through real-time polymerase chain reaction and Western blot.

RESULTSCyclic stretching promoted the expression of ERK1/2, osteocalcin (OCN) mRNA, and bone sialoprotein (BSP) mRNA. The expression of runt-related transcription factor (Runx) 2 protein and mRNA also increased at 3 and 6 h of cyclic stretching. The inhibition of ERK1/2 by U0126 and DN-ERK1/2 suppressed the expressionof Runx2 mRNA, OCN mRNA, BSP mRNA, Runx 2 protein, and p-ERK1/2 protein relative to that in stretched cells without the ERK1/2 inhibitor.

CONCLUSIONSERK1/2 is a critical molecule in the mediation ofthe osteogenic differentiation of hPDLCs under mechanical stimulation. ERK1/2 activation induced the elevation of Runx2 protein levels, which may be involved in the stretch-induced expressions of OCN and BSP.

Objective: To understand the prevalence of facility-based HIV testing and its associated factors among men who have sex with men (MSM) in Beijing city. Methods: An application-based cross-sectional survey was employed to understand HIV site test situation and associated factors. The survey was carried out from May 14^th to 21^st, 2016. Users of a smart phone application for gay dating were recruited and those eligible for this survey were investigated with an online self-administered questionnaire. Information of demographics, sexual behaviors, facility-based HIV testing history and recreational drug abuses were collected. The multivariate logistic regression was used to make comparison among different groups and assess associated factors. Results: A total of 7 494 participants were enrolled in the survey with mean age of (28.81 ± 7.38) years, 87.14% (6 530/7 494) sought sexual partners through internet. The proportion of facility-based HIV testing in 1 year was 42.55% (3 189/7 494), MSM who were 25-29 years had higher proportion of facility-based HIV testing in 1 year, the proportion was 45.56%(1 104/2 423). Among MSM who could insist in using condom during anal sex (50.46% (1 539/3 050)), the proportion of HIV site testing in 1 year was higher. The MSM who reported seeking healthcare for symptoms of a sexually transmitted infections (STIs) in the past year or ever using recreational drug had higher proportion of facility-based HIV testing, the proportions were 56.81% (409/720) and 52.00% (1 340/4 917), respectively. Compared with alone cohabitation, cohabitating was associated with decreased odds of HIV facility-based testing in past 1 year(odds ratio (OR)= 0.79, P<0.001). Compared with homosexual sexual orientation, bisexual sexual orientation was associated with decreased odds of facility-based HIV testing (OR=0.83, P=0.004). With the increasing of number of male anal sex partners, the odds of HIV facility-based testing was increasing (OR=1.31, P<0.001) But with the decreasing of the frequency of condom using with male anal sex partners, the odds of facility-based HIV testing was decreasing (OR=0.85, P=0.014). Using recreational drugs (OR=1.36, P<0.001) and seeking healthcare for symptoms of a STI in the past 1 year (OR=1.73, P<0.001) were associated with decreased odds of HIV site testing. Conclusion MSM in Beijing had lower proportion of facility-based HIV testing in past 1 year. Multiple anal sex partners, using recreational drugs, seeking healthcare for symptoms of a STI in the past year, cohabitating, bisexual sexual orientation, and lower frequency of condom using with male anal sex partners were associated with the odds of HIV facility-based testing in past 1 year.