Objective To construct an enhancer-based prognostic risk prediction model for non-small cell lung cancer (NSCLC) by integrating DNA methylome data and transcriptome data. Methods The weighted gene co-expression network analysis (WGCNA) was used to identify NSCLC related genes from the differentially methylated positions (DMPs) of enhancers. Based on the transcriptome data,the prognostic risk prediction model was constructed using LASSO-Cox regression algorithm. Results Through the analysis on DNA methylome data of NSCLC,19784 DMPs were obtained and their distribution patterns were characterized,including 6089 DMPs of enhancers. WGCNA analysis screened 79 highly correlated DMPs of enhancer with NSCLC from the 6089 DMPs. After analyzing the target genes of 79 DMPs with LASSO-Cox regression based on the transcriptome data,10 genes were used to construct a prognostic risk prediction model. The prognostic risk prediction model was evaluated by calculating the areas under the curve (AUC) of 3-,5-,and 10-year time-dependent receiver operating characteristic (ROC) curves in training set and validation set;and the results showed that the 3-,5-,and 10-year AUC in training set and validation set were all higher than 0.7. Finally,a nomogram was constructed to predict the 3-,5-,and 10-year survival probabilities of NSCLC. Conclusion This study provides new insights into the role of enhancers in NSCLC and has the potential to improve the prognosis by guiding personalized treatment decisions.

Objective To construct an enhancer-based prognostic risk prediction model for non-small cell lung cancer (NSCLC) by integrating DNA methylome data and transcriptome data. Methods The weighted gene co-expression network analysis (WGCNA) was used to identify NSCLC related genes from the differentially methylated positions (DMPs) of enhancers. Based on the transcriptome data,the prognostic risk prediction model was constructed using LASSO-Cox regression algorithm. Results Through the analysis on DNA methylome data of NSCLC,19784 DMPs were obtained and their distribution patterns were characterized,including 6089 DMPs of enhancers. WGCNA analysis screened 79 highly correlated DMPs of enhancer with NSCLC from the 6089 DMPs. After analyzing the target genes of 79 DMPs with LASSO-Cox regression based on the transcriptome data,10 genes were used to construct a prognostic risk prediction model. The prognostic risk prediction model was evaluated by calculating the areas under the curve (AUC) of 3-,5-,and 10-year time-dependent receiver operating characteristic (ROC) curves in training set and validation set;and the results showed that the 3-,5-,and 10-year AUC in training set and validation set were all higher than 0.7. Finally,a nomogram was constructed to predict the 3-,5-,and 10-year survival probabilities of NSCLC. Conclusion This study provides new insights into the role of enhancers in NSCLC and has the potential to improve the prognosis by guiding personalized treatment decisions.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

To investigate the clinical role of T-cell transcription factor (TBX21) and adenylate cyclase 9 antibody (ADCY9) gene polymorphisms in the development of childhood asthma. METHODS: Two hundred Han Chinese wheezing children aged 5 years and younger in Henan region from July 2016 to January 2017 were selected as the study group, and another 100 Han Chinese healthy children aged 5 years and younger in the same period were selected as the control group. Oral mucosal exfoliated cells were collected from both groups, and the genotypes of TBX21 gene rs2240017 polymorphic locus and ADCY9 gene rs2230739 polymorphic locus were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) technique, and the risk level of asthma was assessed based on the test results. The children in the low-risk and high-risk groups were compared in terms of serum immunoglobulin E (IgE) levels, API positivity rate and allergic disease incidence, and the correlation between the risk level of asthma-related genetic polymorphisms and serum IgE levels, API and allergic disease incidence was analyzed. All children were followed up until 6 years of age to confirm the diagnosis of asthma, and the incidence of asthma was compared between the low-risk and high-risk groups. Children with asthma were treated with inhaled glucocorticoids and leukotriene receptor antagonists for 3 months, and the control of asthma and the impairment of lung function were compared between the low-risk and high-risk groups. RESULTS: The genotype detection results of rs2240017 polymorphic locus of TBX21 gene and rs2230739 polymorphic locus of ADCY9 gene in the study group compared with those in the control group were statistically significant (P<0.001). The percentages of CC, CT, and TT genotypes of rs2240017 polymorphic locus of TBX21 gene were 19.50%, 56.00%, and 24.50%, respectively, and the percentages of CC, CG, and GG genotypes of rs2230739 polymorphic locus of ADCY9 gene were 86.00%, 10.00%, and 4.00%, respectively, in 200 children with wheezing; serum IgE level, API positivity rate and allergic disease incidence were higher in the high-risk group than in the low-risk group (P< 0.001, <0.001, 0.021, respectively). The degree of risk of asthma-related gene polymorphisms in children with wheezing was positively correlated with serum IgE levels, API positivity, and the incidence of allergic diseases (P<0.001); the incidence of asthma (81.48%) and impaired lung function (74.07%) were higher in the high-risk group than in the low-risk group (4.90%, 3.50%) (P<0.001). There was no statistically significant difference between the asthma control rate of children with asthma in the high-risk group (79.55%) compared with the asthma control rate of children with asthma in the low-risk group (100.00%) (P=0.433). CONCLUSION: Gene polymorphisms at rs2240017 locus of TBX21 gene and rs2230739 locus of ADCY9 gene are closely associated with asthma development and impaired lung function in children with wheezing.

Objective: To study the relationship between motor coordination, social communication impairment, and restricted/repetitive behaviors (RRBs) in children with autism spectrum disorder (ASD). Methods: A total of 123 ASD children aged 2-12 were recruited from rehabilitation service institutions for autistic children in Guangzhou, including 105 boys and 18 girls. The Developmental Coordination Disorder Questionnaire, Social Communication Questionnaire, and Restrictive Behavior Scale Revised were collected to measure motor coordination, social communication skills and RRBs, respectively. Multiple linear regression was used to explore the association between motor coordination and core symptoms. Results: In children aged 2-5 years old, those without motor coordination deficits scored lower in social interaction (7.73±4.00) than others (9.76±2.90)( Z=-2.29, P <0.05). In children aged 6-12 years old, those without motor coordination deficits scored lower in restricted, repetitive, and stereotyped patterns of behavior (4.22±1.93), repetitive sensory-motor behaviors (3.91±2.63), and insistence on sameness (13.52±10.59) than those with motor coordination deficits (6.11±1.54, 14.00±8.49, 31.33±15.05)( Z=-2.48, -3.83, -3.28, P <0.01)。Multiple linear regression analysis showed that fine motor/handwriting and control during movement were negatively correlated with the severity of social communication impairment and RRBs respectively among children aged 2-5 and 6-12( β=-0.85--0.03, -2.98--0.17, P <0.05). Conclusion Among autistic children, those with motor deficits suffered from more severe core symptoms. Motor assessment should be included in the ASD screening, diagnosis and management. Motor intervention should also be promoted in the rehabilitation in order to improve the prognosis and life quality.

Objective: To investigate the association between parenting style and sleep problems among school aged children with autism spectrum disorder (ASD). Methods: A total of 98 children with ASD aged 6-10 years old and 98 age and gender matched typically developing (TD) children from mainstream schools were recruited. Parenting style and sleep problems were measured via Parent Behavior Inventory (PBI) and Children s Sleep Habits Questionnaire(CSHQ), respectively. The symptom severity and intelligence level were also evaluated. Generalized linear model was used to analyze the relationship between parenting style and sleep problems. Results: There was no statistically significant difference in the parenting style of the two groups of children( P > 0.05 ); weekend sleep time of children with ASD was significantly shorter than that of the TD group [(9.1±0.7)(9.5±0.8)h, P < 0.01 ], and the score of sleep onset delay was significantly higher than that of the TD group[(1.8±0.7)(1.5±0.7), P <0.01]. However, there was no statistically significant difference in the incidence of total sleep problems and various problems between the two groups of children( P >0.05). The parental support/engagement of children with ASD was negatively associated with the total score of sleep problems( β=-2.68, 95%CI =-4.88--0.47), bedtime resistance ( β=-1.65, 95%CI =-2.54--0.77) and sleep anxiety( β=-1.01, 95%CI =-1.70--0.32). The parental hostility/coercion was positively correlated with score of daytime sleepiness( β=1.41, 95%CI =0.53-2.29)( P <0.05). Conclusion Parenting style of support/engagement is associated with lower sleep problems in children with ASD, while hostile/coercion is associated with higher sleep problems. It should be improve parental style to reduce the sleep problems in children with ASD.

Objective: To investigate the associations between early life exposure to particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5 ) and the risk of autism spectrum disorder (ASD) among school aged children. Methods: A total of 165 children with ASD and 165 age and gender matched typical development (TD) children were recruited. Children s basic information were obtained via questionnaires, and the severity of ASD symptoms was assessed with Social Responsiveness Scale (SRS). Early life PM 2.5 exposure (preconception, entire pregnancy, and the first two years after birth) were extracted from the Tracking Air Pollution in China (TAP) datasets. Conditional Logistic regression and generalized linear model were used to evaluate the associations of early life exposure to PM 2.5 with the risk and the ASD severity symptoms, respectively. Results: The PM 2.5 exposure of ASD group during preconception[(55.08±9.34)μg/m 3], entire pregnancy[(50.44±8.71)μg/m 3], the first year after birth [(45.04± 8.25 )μg/m 3] and the second year after birth [(40.19±7.12)μg/m 3] were significant higher than those in TD children [(47.66± 7.63 , 44.19±7.16, 38.95±6.07, 35.76±5.65)μg/m 3]( t =7.94, 7.13, 7.70, 6.32, P <0.05). After adjusting for potential confounding, each increase of 1 μg/m 3 in PM 2.5 was associated with higher risk of ASD during preconception ( OR=1.21, 95%CI =1.13-1.29), entire pregnancy( OR=1.18, 95%CI =1.11-1.26), the first year after birth ( OR=1.30, 95%CI =1.18-1.43) and the second year after birth ( OR=1.29, 95%CI =1.17-1.42). No similar results were observed regarding the analyses of SRS total and sub scale scores( P >0.05). Conclusion Early life exposure to PM 2.5 is relate to the risk of ASD, these findings indicated that more attention should be paid to ambient PM pollution in the early life prevention and control of ASD.

BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cellbased administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intraarticular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

Objectives Comparative analysis on epidemiological characteristics of measles in Minhang District before and after Large scale supplementary immunization activities of measles containing vaccine(MCV) in 2010. Methods Measles incidence data of MCV-SIA in 2010 and the first five years before 2010 (from January 1, 2005 to December 31, 2009), the next five years (from January 1, 2011 to December 31, 2015) and the second five years (from January 1, 2016 to December 31, 2020) after were collected. Descriptive epidemiological method was used for comparative analysis. Results The incidence rate of measles in Minhang District, Shanghai after MCV-SIA in 2010 showed a significant downward trend, The average annual incidence (per 100 0000) in the first 5 years before 2010 was 155.96, SIA was 30.08,The next five years was 29.52, The second five years was 2.84,There was statistical difference in the annual incidence rate between the four groups.（χ²=3165.821，P<0.01）. The annual incidence rate between registered residence and non registered residence population were not statistically different after second SIA years after the SIA（χ²=1.646，P=0.223）The proportion of 8-month-old children under the age of MCV decreased from 15.46% in the first five years of MCV-sia to 5.88%,In the second five years after MCV-sia, the proportion of 10-14 age group increased from 7.81% to 13.83%, The susceptible population of measles before MCV-SIA was less than 8 month old and under the age of MCV initial immunization, no migrant workers with no history of immunization and adults with registered residence. Once there is a source of infection, it is easy to cause the spread of the epidemic. After MCV-SIA, foreign students in international schools and nonworking population became the focus of measles. Of the 95 cases in which measles virus genotypes were available in the next five years, 2 (2.11%) were A genotype, and 93 (97.89%)were the indigenous H1 genotype ; Of the 7 cases in which measles virus genotypes were available in the second five years,7 (100%)were the indigenous H1 genotype . Conclusions After MCV-SIA, the comprehensive measles prevention and control measures can effectively control the incidence and prevalence of measles in Minhang District. But circulation of the indigenous H1 genotype was not interrupted, the work of normalization measures to eliminate measles also needs to cooperate with many departments to strengthen the prevention and control measures of measles in foreign schools and the nonworking population.

Objective: To investigate the relationship between classroom lighting and poor vision of primary and middle school students of poor vision with classroom natural light selecting and artificial lighting, so as to provide reference and basis for the prevention and control of eyesight of primary and middle school students. Methods: A total of 1 734 students from 45 classrooms in 7 primary and secondary schools (2 in primary school, 2 in junior high school, and 1 in vocational school) in Baiyun District, Guangzhou were selected by stratified cluster sampling method for research. The classroom lighting environment was monitored by the illuminometer, the naked eye vision of students was detected by 5 m standard logarithmic vision light box, and the basic information and myopia-related behaviors of students were investigated by questionnaire. And the correlation between poor vision of primary and middle school students and classroom lighting was analyzed. Results: The poor vision rate of primary and middle school students in Baiyun District of Guangzhou was 74.2%(1 286), the girls’ rate(79.7%) was higher than boys’(69.4%), the rate of senior high school students(63.4%) was higher than that of middle school students(81.1%), the rate of vocational school students(82.8%) was higher that of primary school students(60.2%), the rate of resident students(78.5%) was higher than that of non-resident students(69.6%). The results of multivariate analysis after controlling for confangulation factors showed that average illumination on the blackboard, and uneven illumination on the desk were associated with higher risk of poor vision[OR(OR95%CI)=1.51(1.01-2.25), 1.42(1.02-1.98),P<0.05)]. Conclusion Poor eyesight of primary and middle school students in Baiyun District of Guangzhou city is serious, especially that of female students, senior high school students and resident students. There is a significant correlation between classroom lighting and poor vision in primary and middle school students. The blackboard and desk lighting are associated with higher risk of poor vision in primary and middle school students.