Background Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder in children, often diagnosed during school age. The etiology of ADHD remains unclear; however, existing studies suggest that environmental factors, such as exposure to triclosan (TCS), may be associated with the occurrence of ADHD-like symptoms in offspring. Nevertheless, relevant research in China remains limited. Objective To investigate the impact of early pregnancy TCS exposure on ADHD-like symptoms in 7-year-old children. Methods This study was based on the Shanghai Birth Cohort (SBC) and included 662 mother-child pairs. TCS concentrations in early pregnancy urine samples were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Demographic information was collected via questionnaires and medical record abstraction. ADHD-like symptoms in 7-year-old children were first assessed using the Strengths and Difficulties Questionnaire (SDQ). Further differentiation of ADHD-like symptom subtypes (inattentive and hyperactive/impulsive) was conducted using the SNAP-IV, a clinically validated ADHD screening tool. Negative binomial regression models were applied to evaluate the associations between prenatal TCS exposure and hyperactive behavior (SDQ assessment) as well as ADHD-like symptom subtypes (SNAP-IV assessment) in 7-year-old children. Results The positive rate of TCS in early pregnancy urine samples was 91.39%, with median concentrations of 0.69 μg·L⁻¹ and 0.63 μg·g⁻¹ before and after the creatinine adjustment, respectively. The modeling results indicated that prenatal TCS exposure was associated with an increased risk of hyperactive symptoms (SDQ assessment) in 7-year-old children (RR=1.04, 95%CI: 1.02, 1.06); the stratified analyses by children sex revealed similar effects for both boys (RR=1.04, 95%CI: 1.02, 1.07) and girls (RR=1.04, 95%CI: 1.01, 1.07). Further analysis of ADHD-like symptom subtypes showed that prenatal TCS exposure increased the risk of inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.05); the sex-stratified analyses indicated associations between TCS exposure and inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.07) as well as hyperactive/impulsive symptoms (RR=1.04, 95%CI: 1.01, 1.08) in girls. Conclusion Prenatal TCS exposure is associated with an increased risk of ADHD-like symptoms in 7-year-old children, primarily contributing to the risk of the inattention subtype. The impact is more pronounced in girls.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

【Objective】 To explore the correlation between different feeding styles of caregivers and diet quality of children with nutritional problems, in order to provide reference for making effective feeding guidance and intervention strategy. 【Methods】 From January 2022 to August 2023, 2- to 6-year-old children who had been enrolled in kindergartens or nurseries and their caregivers from the combined outpatient department of Child Healthcare and Nutrition in Shanghai Children′s Hospital were selected into this study.The amount of dinner served and consumed was obtained through the three-day dinner intake survey, and the Chinese Healthy Eating Index (CHEI) was calculated.Feeding styles were divided into four groups through the Caregiver Feeding Style Questionnaire.Pearson correlation analysis was used to determine the correlation between served and consumed CHEI score.Chi-square test, t-test and ANOVA were used to compare the differences in CHEI score for dinner consumed in children with different feeding styles. 【Results】 1) Totally 133 parent-child pairs were included in this study.There were 68 boys (51.1%) and 65 girls (48.9%), with an average age of (4.6±0.6) years.2) CHEI scores for dinner served was highly correlated with that for dinner consumed (r=0.90, P<0.05).There was statistically significant difference between the CHEI score for dinner served and consumed by authoritative and authoritarian feeding styles (t=2.538, 1.732, P<0.05).3) After adjusting body shape, children in the authoritative feeding style actually completed a significantly higher diet quality CHEI score than those in the authoritarian feeding style (P<0.05).4)Authoritative and indulgent feeding styles had statistical differences in the distribution of children′s body size (χ²=13.587, P=0.035). 【Conclusions】 Parents with authoritarian feeding style and indulgent feeding style have worse control over their children′s dietary completion.Children with authoritative feeding style have higher dietary quality than those with authoritarian feeding style.Children with indulgent feeding style may have a higher proportion of non-low weight than those with authoritative feeding style.Although feeding style could not reverse the outcome of body shape deviation in children with disease, it may have some positive effects.

Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Objective:The efficacy of using a single electrical or magnetic stimulation for treating pelvic floor dysfunction is limited.This study aims to investigate the efficacy of radiofrequency combined with magnetic stimulation treatment for mild to moderate pelvic organ prolapse. Methods:Patients who completed the treatment in the Third Xiangya Hospital,Central South University were screened,and were divided into 2 groups based on different treatment plans.There were 28 patients who completed magnetic stimulation therapy(the magnetic stimulation therapy group)and 21 patients who completed radiofrequency combined with magnetic stimulation therapy(the combined treatment group).The pelvic organ prolapse quantitation(POP-Q),pelvic floor muscle strength,and pelvic floor ultrasound results were analyzed to assess the efficacy before and after the treatment in both groups,and the POP-Q results of 3 months after the treatment were used to evaluate the maintenance effect of the treatment mode. Results:The POP-Q evaluation results of Aa,Ap,and C points after the treatment in both groups were better than those before the treatment,with statistical significance(all P＜0.05).The Aa point POP-Q result of the combined treatment group was better than that of the magnetic stimulation therapy group,with statistical significance(P＜0.05).Pelvic floor ultrasound evaluation showed that the bladder neck position during the valsalva maneuver in the combined treatment group was higher than that in the magnetic stimulation treatment group,with statistical significance(P＜0.05).The persistence effect of the combined treatment group was long better than that of the magnetic stimulation treatment group,with significant statistical significance(P＜0.01). Conclusion:The combined treatment is more effective and has a longer lasting effect than single magnetic stimulation treatment.

Objective:To explore whether a longitudinal integrated clerkship (LIC) model is more conducive to medical students' post competency and satisfaction with clerkships compared with the traditional block rotation clerkship.Methods:We selected 72 students who participated in graduating clerkships at The First Affiliated Hospital of Harbin Medical University from June 2018 to June 2019. They were equally divided into experimental group and control group to adopt LIC and traditional block rotation clerkship models, respectively. After completing the clerkships, the two groups were evaluated for post competency through objective testing of theoretical medical knowledge and basic clinical skills and rating of the other five competence items by the students themselves and their teachers. At the same time, a questionnaire was delivered to both groups for the degree of satisfaction with clerkships. The t-test and chi-squared test were performed using SPSS 23.0. Results:The objective tests and students' self-evaluation showed that the experimental group had significantly higher scores of theoretical medical knowledge [(8.02±1.11) vs. (7.50±0.97)], basic clinical skills [(7.63±0.90) vs. (6.93±0.73)], medical professional responsibility [(7.74±0.56) vs. (7.31±0.78)], clinical communication [(8.10±1.06) vs. (7.22±0.60)], team work [(7.84±0.62) vs. (7.11±0.69)], literature searching [(6.25±0.60) vs. (4.78±0.84)], and scientific research ability [(4.26±0.88) vs. (2.46±1.20)] compared with the control group (all P<0.05). The experimental group had significantly higher teacher-rated scores of medical professional responsibility [(8.03±0.74) vs. (6.59±0.70)], clinical communication [(7.95±0.73) vs. (6.87±0.67)], team work [(7.96±0.75) vs. (6.95±0.69)], literature searching [(4.84±0.84) vs. (3.30±0.69)], and scientific research ability [(4.53±1.03) vs. (2.70±1.05)] than the control group (all P<0.01). The scores of satisfaction were all higher in the experimental group than in the control group in terms of course arrangement satisfaction [(7.17±0.91) vs. 6.56±0.84)], teacher-student interaction satisfaction [(7.08±0.69) vs. (6.28±0.82)], self-improvement satisfaction [(7.28±0.45) vs. (6.36±0.49)], and clinical work smoothness [(7.72±0.82) vs. (6.81±0.71); all P<0.01]. Conclusion:Compared with the traditional block rotation model, the LIC model is more helpful for improving the post competency of medical students. LIC is a new clinical clerkship model that can potentially replace the traditional block rotation clerkship.

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil < 205.2 μmol/L) and group B (TBil ≥205.2 μmol/L). the two groups were compared in terms of clinical features and 28-day, 90-day, 1-year, and 3-year survival. The t -test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze survival rate, and the log-rank test was used for comparison. Results There were significant differences between the two groups in age( t =3.188, P =0.001) male sex( χ 2 =33.833, P < 0.001), liver failure classification( χ 2 =39.987, P < 0.001), white blood cell count( Z =6.586, P < 0.001), hemoglobin( Z =4.272, P < 0.001), platelet count( Z =3.680, P < 0.001), creatinine( Z =4.505, P < 0.001), total cholesterol( Z =8.644, P < 0.001), Na( Z =2.335, P =0.020), albumin( Z =2.592, P =0.010), HBV DNA( Z =3.703, P < 0.001), Model for End-Stage Liver Disease score( Z =11.828, P < 0.001), and MELD-Na score( Z =8.410, P < 0.001). At baseline, there were significant differences in the incidence rates of ascites and gastrointestinal bleeding between the two groups ( χ 2 =12.036、4.342, P < 0.05). Infection was the most common new-onset complication within 28 days, followed by hepatic encephalopathy, and there was a significant difference in the incidence rate of infection between the two groups ( χ 2 =5.294, P < 0.05). The 28-day transplant-free mortality rate was 21.2% in group A and 29.5% in group B( HR =1.473[95% CI : 1.151~1.886], P =0.005), which was consistent with the clinical feature of a high short-term mortality rate (> 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.

To compare different illness severity scores in predicting mortality risk of extremely low birth weight infants (ELBWI). From January 1st, 2019 to January 1st, 2020, all ELBWI admitted in the Children's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital and the First Affiliated Hospital of Nanjing Medical University were included in the study. ELBWI with admission age ≥1 h, gestational age ≥37 weeks and incomplete data required for scoring were excluded. The clinical data were collected, neonatal critical illness score (NCIS), score for neonatal acute physiology version Ⅱ (SNAP-Ⅱ), simplified version of the score for neonatal acute physiology perinatal extension (SNAPPE-Ⅱ), clinical risk index for babies (CRIB) and CRIB-Ⅱ were calculated. The scores of the fatal group and the survival group were compared, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above illness severity scores for the mortality risk of ELBWI. Pearson correlation analysis was used to analyze the correlation between illness scores and birth weight, illness scores and gestational age. A total of 192 ELBWI were finally included, of whom 114 cases survived (survival group) and 78 cases died (fatal group). There were significant differences in birth weight, gestational age and Apgar scores between fatal group and survival group (all <0.01). There were significant differences in NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ between fatal group and survival group (all <0.01). The CRIB had a relatively higher predictive value for the mortality risk. Its area under the ROC curve (AUC) was 0.787, the sensitivity was 0.678, the specificity was 0.804, and the Youden index was 0.482. The scores of NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ were significantly correlated with birth weight and gestational age (all <0.05). The correlation coefficients of CRIB-Ⅱ and CRIB with birth weight and gestational age were relatively large, and the correlations coefficients of NCIS with birth weight and gestational age were the smallest (0.191 and 0.244, respectively). Among these five illness severity scores, CRIB has better predictive value for the mortality risk in ELBWI. NCIS, which is widely used in China, has relatively lower sensitivity and specificity, and needs to be further revised.
Birth Weight ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Newborn, Diseases/mortality* ; Predictive Value of Tests ; Risk Assessment/methods* ; Severity of Illness Index

ObjectiveTo investigate the value of remote consultation of heart sound acquisition in screening and referral of neonates with congenital heart diseases （CHD） in primary hospitals. MethodsA total of 4 030 neonates with non-critical diseases were selected. They were born in Shanghai Pudong New Area Maternal and Child Health Hospital from November 5， 2019 to March 31， 2021. After birth， routine cardiac auscultation was performed and remote consultation of heart sound collection were performed at the same time in combination with percutaneous oxygen saturation measurement to screen CHD. The children with any positive screening index were advised to verify the diagnosis by cardiac ultrasound examination in Shanghai Children's Medical Center. The diagnostic value of different screening methods was compared. ResultsA total of 110 cases were detected positive by routine screening. Among them， 16 cases were lost to follow-up， and 46 cases were confirmed by cardiac ultrasound examination， with a positive diagnosis rate of 48.94% （46/94）. A total of 51 cases were detected positive by routine screening and remote consultation of heart sound collection simultaneously. Among them， 42 cases were confirmed by cardiac ultrasound examination， with a positive diagnosis rate of 82.35% （42/51）. The difference between the two positive diagnosis rates was statistically significant （P<0.001）. ConclusionRemote consultation of heart sound acquisition on the basis of routine neonatal CHD screening can effectively improve the positive diagnosis rate of CHD screening in primary hospitals， and reduce unnecessary referrals. This method is simple and feasible. It has practical value in primary hospitals that lack professional technicians for the diagnosis and treatment of CHD.