ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

Objective:To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase ( PAH) gene among patients with PAH deficiency. Methods:Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed.Results:Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor three PAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and three PAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on the PAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion:When the c. 158G>A variant and other pathogenic variants are arranged in cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.

Purpose/Significance To quantitatively analyze and evaluate 26 health informatization construction policies issued at the national level,so as to provide basis for improving related policies.Method/Process Based on the policy modeling consistency(PMC)index model,a health informatization construction policy evaluation index system is constructed,which includes 9 first-level indicators and 36 second-level indicators.Appling it to the evaluation of various policy texts,and the health informatization construction policies are analyzed in a holistic and concrete way.Result/Conclusion The overall score of the health informatization construction policies is ex-cellent.2 policies are at the perfect level,80.6％of policies are at the excellent level,and there are no bad level policy texts.However,the driving force of the policy and the balance of policy recipients need to be further improved.

Objective:To assess the effects of intervention measures on the quality control of health examination institutions in Dalian City.Methods:This cross-sectional study encompassed a comprehensive evaluation of 40 physical examination institutions in Dalian City. Interrupted time series analysis was employed to examine the changes in level and slope of processing rates for significant abnormal health examination results, chief inspection physician qualification rates, and completion rates of basic health examination items before (January 2020 to July 2021) and after (August 2021 to July 2022) intervention. An interrupted time series analysis diagram was generated.Results:After the implementation of intervention measures, the processing rate of significant abnormal results in public physical examination institutions reached 93.52%, while the qualification rate of chief inspection physicians was as high as 98.86%. And completion rate of basic health examination items was 93.86%. The rates of handling important abnormal results in health check-ups at private healthcare institutions before intervention, 1 month after intervention, and long-term intervention showed an upward trend of 1.374%, 0.229%, and 0.664%, respectively ( t=8.61, 12.21, and 108.61, all P<0.05). The qualification rate of chief inspection physicians in public physical examination institutions exhibited an increase of 0.227% and 0.155% before and after the intervention respectively ( t=6.74 and 617.67, all P<0.05). The completion rates of basic health check-up items in public healthcare institutions showed an upward trend before intervention, 1 month after intervention, and long-term intervention, with a rate of 0.446%, 0.067%, and 0.745%, respectively ( t=24.95, 3.25, 138.80, all P<0.05). Conclusions:The implementation of quality control intervention measures for health check-ups has significantly improved the quality control of health examination institutions in Dalian City.

The most common subtype of lung cancer is non-small cell lung cancer (NSCLC), which has a poor prognosis and seriously threatens the health of human beings. The multidisciplinary comprehensive treatment model has gradually become the mainstream of NSCLC treatment. Traditional Chinese medicine (TCM) can be used effectively either as an adjunctive therapy or alone throughout the NSCLC therapy, which has a significant impact on survival, quality of life, and reduction of toxicity. Therefore, this paper reviewed the theoretical basis, the latest clinical application, and combined treatment mechanisms in order to explore the advantage stage of TCM treatment and the synergistic therapeutic mechanisms.

Objective: To explore the effect of miniscrew-assisted rapid palatal expansion (MARPE) on mandible position in the treatment of adult skeletal Class Ⅰ malocclusion with maxillary transverse deficiency. Methods: In this retrospective study, 20 cases of adult skeletal Class Ⅰ malocclusion with maxillary transverse deficiency treated with MARPE in our hospital from July 2019 to March 2022 were selected as research objects. CBCT data of three time points before treatment (T0), immediately after expansion (T1) and six months after retention (T2) were collected. The head position was standardized and calibrated by Dolphin software, and then mandible landmarks (left and right Condylion, left and right Gonion, Menton) were positioned. The linear distance changes of each landmark relative to the reference plane of coronal plane, axial plane and sagittal plane were measured, which represented the sagittal, vertical and horizontal displacement of mandible respectively. Repeated measurement ANOVA and LSD multiple comparison were used to evaluate the position change of each landmark. Results : The Menton and right Gonion rotated clockwise at T1, and relapsed to the initial position at T2. No lateral displacement of Menton was found. Conclusion When MARPE is used to treat skeletal Class Ⅰ malocclusion with maxillary transverse deficiency, it causes a transient clockwise rotation of the mandiblar. The mandible does not show sagittal, vertical and horizontal position changes in long-term evaluation.

Cohort study is one of the important research methods in analytical epidemiology because of its clear time sequence relationship, which is better than other observational studies in demonstrating causal association. However, screening diagnosis or other methods are often used to exclude the individuals with outcome events during the enrollment process of the subjects in cohort studies. The accuracy of screening diagnosis and the effectiveness of exclusion will affect the accuracy of the baseline status assessment of the subjects included in the study, which may lead to the causal time sequence reversal of exposure-outcome in the estimation of causal effect. Landmark analysis can be used to control reverse causality by excluding subjects with potentially unknown expose-outcome timing. In this paper, we describe the basic principles and analytical steps of landmark analysis, and use data from the Chinese Longitudinal Healthy Longevity Survey to explore the relationship between physical activity and frailty, and introduce the specific application of landmark analysis for the purpose of facilitating its application and inferring causal effects more accurately in cohort studies.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

ObjectiveTo explore the sensory processing characteristics of preschool children with autism spectrum disorder （ASD）， and to provide a theoretical basis for early screening and intervention training of ASD. MethodsA total of 215 preschool children with ASD and170 typically developed （TD） children were investigated with a basic situation questionnaire and sensory processing measure （SPM）. The two groups were stratified according to age and gender， and the differences of scores in sensory domains were compared to analyze the sensory processing characteristics of preschool children with ASD. ResultsThe scores of social participation， vision， hearing， touch， taste and smell， body awareness， balance and motion， planning and ideas， and total sensory system in children with ASD were all higher than those in children with TD （all P<0.01）. The highest degree of abnormality was found in hearing and the lowest degree in taste and smell in children with ASD. The results of Spearman correlation analysis showed that in the 4-year-old and 5-year-old children with ASD， the scores of vision （r_s=-0.200， P= 0.033） and hearing （r_s=-0.194， P=0.040） decreased with age. There was no correlation between the scores of other developmental quotients and age （all P>0.05）. Boys and girls with ASD had higher scores in all developmental quotients than TD children （P<0.01）. However， there was no significant gender difference in any developmental quotients of ASD children （all P>0.05）. ConclusionSensory processing abnormalities are common in preschool children with ASD， which are different from those of TD children in multiple sensory domains. Sensory processing abnormalities may be used as an indicator for early screening of ASD， and it is necessary to conduct corresponding intervention training for sensory processing abnormalities in children with ASD.

Objective:To study the efficacy and drug-related adverse reactions of long-term appli-cation of biological anti-rheumatic drugs (bDMARDs) to patients with ankylosing spondylitis (AS), and provide reference for clinical diagnosis and treatment.Methods:We retrospectively analyzed the clinical data of AS patients who were followed-up for more than 5 years in the Department of Rheumatology and Immunology of Peking University Shenzhen Hospital. The patients treated with bDMARDs alone or combined with traditional antirheumatic drugs were included as the treatment group, while those who did not receive biological or non-biological antirheumatic therapy were included as the control group. The data collected included clinical sym-ptoms, inflammatory biomarkers, imaging results, drug applications and drug-related adverse reactions, etc. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by Mann-Whitney U test. Paired test was used for statistical processing before and after treatment. Results:We collected the data of 114 eligible patients, including 64 in the treatment group and 50 in the control group. There were no significant differences in baseline data between the 2 groups, including mean follow-up time, course of disease, age, sex ratio, HLA-B27 positive rate, morning stiffness duration, night pain, peripheral arthritis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging. After 5 years, patients in the treatment group had shorter morning stiffness [(3±7) min vs (26±37) min, t=4.827, P<0.01], lower nighttime pain rates [(3/64, 4.8%) vs (29/50,58.0%), χ2=38.329, P<0.01], lower ESR level [(14±14) mm/1 h vs (20±18) mm/1 h, t=2.102, P=0.038], lower CRP level [(7±8) mg/L vs (14±19) mg/L, t=2.431, P=0.017], and lower progression rate of sacroiliac arthritis [(18/64, 28.1%) vs (35/50, 70.0%), χ2=19.786, P<0.01], than the control group. The main drug-related adverse reactions in the treatment groupincluded reversible leucopenia, elevated transaminase level, redness and swelling at the injection site. Conclusion:Biologics treatment for more than 3 consecutive years can effectively control the clinical symptoms of most AS patients, reduce inflammatory indicators and delay the imaging progression of the sacroiliac joint. Without treatment, the imaging progress of the sacroiliac joint in AS patients could be 70% after 5 years.