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ObjectiveTo analyze the effects of tooth brushing frequency on blood indicators among adolescents and to preliminarily explore the effects of tooth brushing frequency on general health.MethodsUsing convenience sampling method, the study included the students of class 2021 of Jining No. 7 Middle School and student athletes from the Jining Sports Training Center. Univariate and multivariate linear regression analyses were used to investigate the correlation between tooth brushing frequency and blood indicators such as eosinophil percentage (EOS%), eosinophil count (EOS#), basophil percentage (BAS%), basophil count (BAS#), superoxide dismutase (SOD), insulin-like growth factor 1 (IGF-1) and uric acid (UA).ResultsA total of 305 students were included (167 from Jining No. 7 Middle School, 138 from Jining Sports Training Centre), with 192 (62.95%) males and 113 (37.05%) females. They were divided into three groups based on daily teeth brushing frequency: ≤1 time (40.33%, 123/305), 2 times (53.77%, 164/305), and ≥3 times (5.90%, 18/305).Univariate linear regression analysis showed that brushing twice daily was negatively correlated with EOS%, EOS#, BAS%, and BAS#(all β > 0, all P < 0.05), and positively correlated with SOD and IGF-1(both β < 0, P=0.028, P=0.007). Brushing three or more times daily was negatively correlated with UA[β(95% CI): -0.16(-0.27~0.04), P=0.008]. Multivariate linear regression analysis showed that brushing twice daily was negatively correlated with BAS%(β < 0, P=0.042) and positively correlated with SOD and IGF-1(both β > 0, P=0.036, P=0.012), while brushing three or more times daily was negatively correlated with UA(β < 0, P=0.026). Subgroup analysis revealed that in male adolescents, brushing twice daily was positively correlated with IGF-1(β > 0, P=0.044), and in female adolescents, brushing three or more times daily was negatively correlated with UA(β < 0, P=0.014).ConclusionThe adolescent tooth brushing frequency correlates with several blood indicators affecting general health, suggesting that there may be a potential association between oral health and general health.

Large bone tissue defects present a significant clinical challenge due to the lack of stem cells and an osteogenic microenvironment, leading to fibrotic healing and impaired bone regeneration. Microsphere-based cell-on three-dimensional (3D) culture systems show great promise for constructing osteogenic microtissues. However, the underlying mechanisms require further investigation. In this study, we propose a simple, scalable framework for highly efficient osteogenic microtissue construction, utilizing gelatin methacryloyl (GelMA) microspheres and dental pulp stem cells (DPSCs). The GelMA microspheres provide an extensive, scalable 3D framework for the autonomous adhesion, migration, and proliferation of DPSCs. Within the enormous 3D space created by the microspheres, DPSCs anchor to the microspheres and neighboring cells, inducing intrinsic tensile stress and simulating a mechanical force akin to "rock climbing training". Transcriptomic sequencing results reveal that the 3D spatial and mechanical microenvironment modulates biological processes involved in cell adhesion, extracellular matrix organization, and the positive regulation of cell migration. Further investigations demonstrate that triggering the FAK/YAP pathway mediate mechanical driven differentiation of DPSCs into the osteoblastic lineage in the excellent osteogenic microtissues. Moreover, this simple scalable 3D framework strategy is expected to enable the efficient and large-scale preparation of stem cell-based microtissues.

Oral health is closely related to systemic health. Common chronic oral diseases, periodontitis and periapical inflammation for example, not only affect the health of oral soft and hard tissues including the alveolar bone and gums, but may also cause changes in systemic conditions such as chronic low-grade inflammation, elevated oxidative stress levels, and dysbiosis of the microbiota. These changes in systemic health can exacerbate the progression of obesity. Therefore, through proactive oral health interventions such as maintaining good oral hygiene habits, modifying dietary structures, and undergoing oral examinations, it is possible to effectively prevent and alleviate inflammatory oral diseases, and actively intervene in obesity. This article delves into the impact of inflammatory oral diseases on obesity and their underlying mechanisms, defines the concept of 'oral proactive healthcare', and systematically summarizes their preventive and therapeutic effects on inflammatory oral diseases, thereby demonstrating the potential of improving obesity through proactive oral health strategies.

AIM:To build a facial image database and to explore the diagnostic efficacy and influencing factors of the artificial intelligence-based facial recognition (AI-FR) system for multiple endocrine and metabolic syndromes.METHODS:Individuals with multiple endocrine and metabolic syndromes and healthy controls were included from public literature and databases. In this facial image database, facial images and clinical data were collected for each participant and dFRI (disease facial recognition intensity) was calculated to quantify facial complexity of each syndrome. AI-FR diagnosis models were trained for each disease using three algorithms: support vector machine (SVM), principal component analysis k-nearest neighbor (PCA-KNN), and adaptive boosting (AdaBoost). Diagnostic performance was evaluated. Optimal efficacy was achieved as the best index among the three models. Effect factors of AI-FR diagnosis were explored with regression analysis.RESULTS:462 cases of 10 endocrine and metabolic syndromes and 2310 controls were included into the facial image database. The AI-FR diagnostic models showed diagnostic accuracies of 0.827-0.920 with SVM, 0.766-0.890 with PCA-KNN, and 0.818-0.935 with AdaBoost. Higher dFRI was associated with higher optimal area under the curve (AUC) (P = 0.035). No significant correlation was observed between the sample size of the training set and diagnostic performance.CONCLUSIONS:A multi-ethnic, multi-regional, and multi-disease facial database for 10 endocrine and metabolic syndromes was built. AI-FR models displayed ideal diagnostic performance. dFRI proved associated with the diagnostic performance, suggesting inherent facial features might contribute to the performance of AI-FR models.

Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder with considerable clinical heterogeneity. To further characterize the syndrome's heterogeneity, we applied latent class analysis (LCA) on reported cases to identify phenotypic subtypes. By searching PubMed, Embase, China National Knowledge Infrastructure and Wanfang databases from inception to February 2024, we enrolled 97 cases with nonsense, frameshift or missense variants in the AHDC1 gene. LCA was based on the following 6 phenotypes with moderate occurrence and low missingness: ataxia, seizure, autism, sleep apnea, short stature and scoliosis. After excluding cases with missing data on all LCA variables or with unmatched phenotype-genotype information, a total of 85 cases were selected for LCA. Models with 1-5 classes were compared based on Akaike Information Criterion, Bayesian Information Criterion, Sample-Size Adjusted BIC and entropy. We used multinomial logistic regression (MLR) analyses to investigate the phenotype-genotype association and potential predictors for class membership. LCA revealed 3 distinct classes labeled as Ataxia subtype (n = 11 [12.9%]), Sleep apnea & short stature subtype (n = 23 [27.1%]) and Neuropsychological subtype (n = 51 [60.0%]). The commonest Neuropsychological subtype was characterized by high estimated probabilities of seizure, ataxia and autism. By adjusting for sex, age and variant type, MLR showed no significant association between phenotypic subtype and variant position. Age and variant type were identified as predictors of class membership. The findings of this review offer novel insights for different presentations of XGS. It is possible to deliver targeted monitoring and treatment for each subtype in the early stage.

BACKGROUND:The treatment of craniopharyngiomas (CPs) poses challenges due to their proximity to critical neural structures, the risk of serious complications, and the impairment of quality of life after treatment. However, long-term prognostic data are still scarce. Therefore, the purpose of this retrospective study is to evaluate the long-term outcomes of patients with CPs after treatment. MATERIAL AND METHOD:Our center retrospectively collected data on 83 children and adolescents who underwent craniopharyngioma surgery between 2001 and 2020. The medical records and radiological examination results of the patient were reviewed. RESULTS:Outcomes were analysed for 80/83 patients who completed follow-up: 50 males (62.5%) and 30 females (37.5%), the median age at the time of diagnosis 8.4 (5.3-12.2) years. The median follow-up time was 136 (61-280) months. The 5-, 10- and 15-year overall survival (OS) rates were 100%, 98.3%, and 94.6%, respectively. Accordingly, the disease-specific survival (DSS) rates were 100%, 98.3% and 94.6%, respectively. Overall progression-free survival (PFS) rates after 5, 10 and 15 years of follow-up in the entire group were 85.4%, 72.2% and 70.1%, respectively. Multivariate analysis found that surgical resection grade was only associated with PFS outcomes [ HR = 0.031 (95% CI: 0.006, 0.163), P < 0.001], without improving OS or DSS. After undergoing recombinant human growth hormone (rhGH) replacement therapy, the total cholesterol (TC) level decreased by 0.90 mmol/L compared to baseline (P = 0.002), and the low-density lipoprotein cholesterol (LDL-C) level decreased by 0.73 mmol/L compared to baseline (P = 0.010). For liver function, compared with baseline data, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) showed a downward trend, but did not reach a statistically significant level (P > 0.05). CONCLUSION:Surgical treatment of CPs provides good long-time OS and DSS, even though combined with radiotherapy in only selected cases. Gross total resection (GTR) is individual positive prognostic factor. rhGH replacement could improve CPs lipid profile.

ObjectiveTo evaluate the correlation between ultrasound ossification ratio(OR) and exercise intensity among adolescents.MethodsThis cross-sectional study used stratified sampling to select adolescents aged 11-15 years from a sports school and some ordinary middle schools in Shandong Province in June 2023. The participants were divided into two groups: competitive sports group (high exercise intensity), and general sports group (moderate exercise intensity), based on their exercise intensity. Ultrasound images of long bones from nine body regions (including 3 upper limb bones and 6 lower limb bones) were collected for both groups. Two sonographers interpreted the images and calculated the ultrasound OR values (the ratio of ossification center length to epiphyseal length on the standard ultrasound section). The intraclass correlation coefficient (ICC) was used to assess the consistency of image interpretation between the observers. Differences in ultrasound OR values between the two groups were compared, and multivariate Logistic regression analysis was performed to assess the correlation between ultrasound OR values and exercise intensity.ResultsA total of 252 adolescents who met the inclusion and exclusion criteria were included, with 154 in the competitive sports group (97 males and 57 females) and 98 in the general sports group (52 males and 46 females). The median height and average daily exercise duration were significantly higher in the competitive sports group than in the general sports group (all P < 0.001). The overall ICC for the interpretation of ultrasound OR values of long bones at 9 sites in 50 adolescents by the two sonographers was 0.930 (range: 0.853-0.964), indicating excellent inter-observer consistency. The medial femoral ultrasound OR values were higher in the competitive sports group than in the general sports group for both males and females (males: 0.87±0.07 vs. 0.84±0.04, P=0.025; females: 0.90±0.06 vs.0.85±0.14, P=0.027). Additionally, the differences in ultrasound OR values between the groups were observed in the lateral femoral and fibular bones in males and the radial bone in females (all P < 0.05). Multivariate Logistic regression analysis showed that the reciprocal of the medial femoral ultrasound OR value was correlated with exercise intensity (OR=0.046, 95% CI: 0.012-0.145, P=0.043), indicating that a decrease of 0.1 in the reciprocal of the medial femoral ultrasound OR value (equivalent to an increase of approximately 0.05-0.10 in the ultrasound OR value) was associated with a 2.17-fold increase in the likelihood of high-intensity exercise.ConclusionsThe medial femoral ultrasound OR value was correlated with exercise intensity among adolescents. This indicator may serve as an objective imaging parameter for assessing whether adolescent exercise meets recommended standards.

Phenotypic drug discovery (PDD), which involves harnessing biological systems directly to uncover effective drugs, has undergone a resurgence in recent years. The rapid advancement of artificial intelligence (AI) over the past few years presents numerous opportunities for augmenting phenotypic drug screening on microfluidic platforms, leveraging its predictive capabilities, data analysis, efficient data processing, etc. Microfluidics coupled with AI is poised to revolutionize the landscape of phenotypic drug discovery. By integrating advanced microfluidic platforms with AI algorithms, researchers can rapidly screen large libraries of compounds, identify novel drug candidates, and elucidate complex biological pathways with unprecedented speed and efficiency. This review provides an overview of recent advances and challenges in AI-based microfluidics and their applications in drug discovery. We discuss the synergistic combination of microfluidic systems for high-throughput screening and AI-driven analysis for phenotype characterization, drug-target interactions, and predictive modeling. In addition, we highlight the potential of AI-powered microfluidics to achieve an automated drug screening system. Overall, AI-powered microfluidics represents a promising approach to shaping the future of phenotypic drug discovery by enabling rapid, cost-effective, and accurate identification of therapeutically relevant compounds.

OBJECTIVE:Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs.MATERIALS AND METHODS:The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.RESULTS:According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level.CONCLUSION:In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

Background: Sodium fluctuation is independently associated with clinical deterioration. We developed and validated a prognostic index based on sodium fluctuation for risk stratification and in-hospital monitoring. Methods: This study included 33,323 adult patients hospitalized at a tertiary care hospital in 2014. The first 28,279 hospitalizations were analyzed to develop the model and then the validity of the model was tested using data from 5044 subsequent hospitalizations. We predict in-hospital mortality using age, comorbidity, range of sodium fluctuation, and duration of sodium fluctuation, abbreviated as CARDS. Results: In-hospital mortality was similar in the derivation (0.6%) and validation (0.4%) cohorts. In the derivation cohort, four independent risk factors for mortality were identified using logistic regression: age (66–75, 2 points; >75, 3 points); Charlson comorbidity index (>2, 5 points); range of sodium fluctuation (7–10, 4 points; >10, 10 points); and duration of fluctuation (≤3, 3 points). The AUC was 0.907 (95% CI: 0.885–0.928) in the derivation cohort and 0.932 (95% CI: 0.895–0.970) in the validation cohort. In the derivation cohort, in-hospital mortality was 0.106% in the low-risk group (0–7 points), 1.076% in the intermediate-risk group (8–14 points), and 8.463% in the high-risk group (15–21 points). In the validation cohort, in-hospital mortality was 0.049% in the low-risk group, 1.064% in the intermediate-risk group, and 8.403% in the high-risk group. Conclusions: These results suggest that patients at low, intermediate, and high risk for in-hospital mortality may be identified by CARDS mainly based on sodium fluctuation.

Purpose : To report a case series of four patients with isolated growth hormone deficiency (IGHD) type I from two Chinese pedigrees and to elucidate phenotype-genotype correlation of IGHD type I and II with GH1 gene alterations in the literature. Methods: Whole exome sequencing (WES) were performed and a literature review was conducted. Results : Four patients presented with extreme growth retardation (height -4.74 to -6.50 SDS) and undetectable peak growth hormone (GH) during GH stimulating test. WES revealed a novel homozygous nonsense mutation, c.316delC (p.L106Cfs*35), in GH1 gene in the the first pedigree. Deletions of exon 1-5 in GH1 gene were identified in the second pedigree. Ideal catch-up growth after GH treatment was achieved. 94 patients with IGHD type I and 240 patients with IGHD type IIwere included in literature review. Patients with IGHD type I exhibited younger age (3.2 vs 6.0 years, P<0.001), more severe growth retardation (median height -6.50 vs -3.84 SDS, P<0.001), lower peak GH levels (0.05 vs 1.70 ng/ml, P<0.001) and a higher dosage of GH (0.22 vs 0.17 mg/kg/week, P=0.012) compared to patients with IGHD type II. Gross deletions constituted 72.3% of IGHD type I cases, while splicing mutations and missense mutations comprised 54.2% and 45.0% of IGHD type II cases. Height SDS after GH treatment in IGHD type II and in patients with mutations affecting splicing was negatively associated with age at diagnosis. Conclusion : IGHD type I is a rare inherited disease. Earlydiagnosis and initiating treatment may lead to a better prognosis.

Objective To analyze the clinical characteristics and genotype of a patient with congenital systemic lip-odystrophy(CGL)type 1 associated with exudative xanthoma caused by AGPAT2 gene mutation,and to provide ev-idence for clinical and genetic diagnosis of the disease.Methods Clinical data of the patient such as medical histo-ry,physical examination and laboratory examination were collected.Peripheral venous blood was collected for whole exome sequencing analysis and Sanger sequencing verification,and treatment was provided to patients according to the changes of condition.Results The clinical manifestations of the patient were subcutaneous fat reduction,fatty liver,spleen enlargement,kidney enlargement,high blood sugar and lipids,severe insulin resistance,scattered yellow rash on limbs,which was confirmed as xanthoma.The results of whole exon sequencing showed that the AGPAT2 gene of the patient had a heterozygous nonsense mutation of c.202C＞T:p.R68∗and c.646A＞T:p.K216∗,and the former was the pathogenic mutation site.Follow-up therapy covers improvement of lifestyle,low-fat diet and regular exercise.The rashes subsided after active lipid-lowering therapy.Conclusions Apart from typical lipody-strophy,the patient was accompanied by exanthemous xanthoma.No CGL1 patient with exanthemous xanthoma has been reported in the domestic literature database up to now,and the genetic test results showed that there was a c.202C＞T heterozygous mutation of AGPAT2 gene.This gene site has not been reported in the literature,and its functional verification needs to be further studied.

Context:The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients.Objective:To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement.Methods:Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy.Results:Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (-0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement.Conclusion:The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.

BACKGROUND:The relationship between maternal thyroid function and pregnancy outcomes remains controversial and the safe range of TSH is still unclear in women planning pregnancy. METHODS:This population-based cohort study enrolled Chinese women who became pregnant in 30 provinces from 2010 to 2012 from the National Free Preconception Checkups Project. The maternal TSH level within 6 months before pregnancy and different pregnancy outcomes were collected and analyzed using restricted cubic spline regression model for dose-response relationship and potential optimal cutoff values. Logistic regression was used to reveal the relationship between different TSH groups and the risk of adverse outcomes. RESULTS:Among 175 112 women, a J-shaped association was revealed between TSH and large for gestational age (LGA; P < 0.001). When TSH was lower than 1.27 or 0.91 mIU/L, lower TSH was associated with higher odds ratio of low birth weight (LBW; P = 0.003) or preterm delivery (P < 0.001). There was no significant association of preconception TSH with SGA, macrosomia, fetal anomalies, stillbirth, natural or induced abortion, and cesarean delivery. The range of TSH for odds ratio lower than 1.0 was within 0.91 to 1.82 mIU/L in dose-response association. Compared with TSH 0.91 to 1.82 mIU/L, TSH low (< 0.40 mIU/L and 0.40-0.90 mIU/L) and high (1.83-2.49 mIU/L, 2.50-3.99 mIU/L, and >4.00 mIU/L) were associated with higher risk of preterm delivery and LGA. There was no significant association between TSH groups and the risk of LBW except for TSH < 0.40 mIU/L. CONCLUSION:Preconception TSH was associated with preterm delivery, LGA, and LBW. Preconception TSH had a bidirectional effect on LGA, indicating a potential mechanism regarding influence of TSH on birth weight. TSH within 0.91 to 1.82 mIU/L was the potential safe range for preconception women.

目的 观察循证干预对2型糖尿病并发下肢血管病变患者生活质量的效果.方法 收集2018年11月至2020年11月中国医学科学院北京协和医院收治的108例2型糖尿病并发下肢血管病变患者的临床资料.根据干预方法不同将患者分为对照组和观察组,每组54例.对照组患者采取常规干预措施,观察组患者在常规干预基础上采取循证干预措施,比较两组患者入院时及出院时的血糖水平,包括空腹血糖(FBG)和餐后2 h血糖(2 h PG);双下肢供血情况及生活质量[糖尿病生存质量特异性量表(DSQL)评分].结果 两组患者入院时的血糖水平、踝肱指数(ABI)和趾肱指数(TBI)比较,差异均无统计学意义(P>0.05);观察组患者出院时的FBG、2 h PG均低于对照组患者,ABI、TBI均高于对照组患者,差异均有统计学意义(P<0.05).两组患者入院时的DSQL评分比较,差异无统计学意义(P>0.05);观察组患者出院时的DSQL评分低于对照组患者,差异有统计学意义(P=0.001).结论 对2型糖尿病并发下肢血管病变患者应用循证干预可降低其血糖水平,改善双下肢供血情况,提高患者的生活质量,值得推广.

Diseases not only manifest as internal structural and functional abnormalities, but also have facial characteristics and appearance deformities. Specific facial phenotypes are potential diagnostic markers, especially for endocrine and metabolic syndromes, genetic disorders, facial neuromuscular diseases, etc. The technology of facial recognition (FR) has been developed for more than a half century, but research in automated identification applied in clinical medicine has exploded only in the last decade. Artificial-intelligence-based FR has been found to have superior performance in diagnosis of diseases. This interdisciplinary field is promising for the optimization of the screening and diagnosis process and assisting in clinical evaluation and decision-making. However, only a few instances have been translated to practical use, and there is need of an overview for integration and future perspectives. This review mainly focuses on the leading edge of technology and applications in varieties of disease, and discusses implications for further exploration.

BackgroundFine particulate matter (PM2.5), one of the most common air pollutants worldwide, has been associated with many adverse birth outcomes in some studies. Pre-pregnancy body mass index (BMI) is an important indicator of maternal obesity that may also contribute to a wide range of birthweight outcomes. Both PM2.5 and maternal obesity have been found associated with issues on neonatal birthweight respectively, and more attentions and interests are focusing on their combined effect on pregnancy outcomes.PurposeTo explore the modifying effect of pre-pregnancy BMI on the association between gestational PM2.5 and birthweight; to investigate the interactive effect between gestational PM2.5 and pre-pregnancy BMI on birthweight among pregnant women during three trimesters and the whole pregnancy.MethodsThis nationwide cohort study used the National Free Preconception Health Examination Project (NFPHEP) data collected from January 1, 2010, to December 31, 2012. A total population of 248,501 Chinese women from 220 counties registered this project. Pre-pregnancy BMI as a common anthropometric examination was collected during preconception investigation, and gestational PM2.5 was derived from a hindcast model for historical PM2.5 estimation from satellite-retrieved aerosol optic depth. Subgroup analysis was conducted to explore a potential modifying effect on the association between PM2.5 and birthweight during pregnancy by four pre-pregnancy BMI subgroups. Interaction analysis by introducing product terms to multivariable linear regression was also used to examine whether there was an interactive relationship between PM2.5 and pre-pregnancy BMI.ResultsTotally, 193,461 participants were included in our study. The average concentration of PM2.5 was 75.33 μg/m3. Higher exposure of PM2.5 during the entire pregnancy was associated with higher birthweight (17.15 g per 10 μg/m3; 95% CI:16.15, 18.17). Each 10 μg/m3 increase in PM2.5 during the first, second, and third trimesters was associated with increases in birthweight by 14.93 g (95%CI: 13.96, 15.89), 13.75 g (95% CI: 12.81, 14.69), and 8.79 g (95% CI: 8.09, 9.49), respectively. Higher pre-pregnancy BMI per kg/m2 was associated with an increase of birthweight by 7.012 g (95% CI: 6.121, 7.902). Product terms between PM2.5 and pre-pregnancy BMI were significant for the first, second trimesters, and the entire duration of pregnancy.ConclusionsOur results found both gestational PM2.5 exposure and pre-pregnancy BMI respectively correlated with the increase of birthweight. A negative interaction between pre-pregnancy BMI and gestational PM2.5 was discovered in term of birthweight gain. Avoidance of high-dose exposure to PM2.5 during the early and middle stages of pregnancy and pre-pregnancy overweight/obesity may help prevent high birthweight.

Abstract Objectives This study aimed to compare the efficacy, safety and metabolic effects of once-weekly pegylated human growth hormone (PEG-rhGH) with daily rhGH in patients with growth hormone deficiency (GHD). Design 48 patients enrolled in this 12-month single-center, open-label, prospective, randomized controlled trial is allocated to PEG-rhGH 0.12 mg/kg/w and 0.20 mg/kg/w treatment. Besides, the control group allocated 23 patients treated with daily rhGH 0.28 mg/kg/w matched with sex, age, and baseline IGF-1 levels. The primary endpoint included height velocity (HV) and IGF-1 increase at the end of treatment. Other parameters associated with growth, metabolism and safety were also monitored. Results In terms of HV increase, the efficacy of PEG-rhGH dosed at 0.12 mg/kg/w and 0.20 mg/kg/w was comparable to that of daily rhGH dosed at 0.28 mg/kg/w after 3, 6 and 12 treatment (p>0.05). IGF-1 concentration and IGF-1 SDS were both elevated significantly at 3, 6 and 12 months (p=0.000) into normal range following PEG-rhGH treatment. BMI SDS elevated after PEG-rhGH treatment for 3, 6 and 12 months (p=0.000). HbA1c elevated after 3 and 12 months (p=0.009) and METS-IR elevated after 6 months (p=0.019) compared with baseline. The differences of other metabolic indexes (such as blood glucose, blood lipid, etc.) have no statistical significance (p>0.05). No severe adverse event was observed among the three groups. Conclusions The efficacy and safety were promising and comparable between once-weekly PEG-rhGH and daily rhGH injection within 12 months. The negative influence on glucose homeostasis needed attention and monitoring.