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.

ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L^-1 and 0.305 μg·L^-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.

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 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】 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.

The retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity reported in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASDs). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. In this work, we reveal that neural activity in the retrosplenial agranular cortex (RSA), a subregion of the retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. This up-down phase of RSA neurons is crucial for normal social behaviors. Parvalbumin-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to the RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input rescued the social behavior defects in an ASD mouse model. This work suggests a neural mechanism for the salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.
Animals ; Social Behavior ; CA1 Region, Hippocampal/physiology* ; Mice ; Male ; Autism Spectrum Disorder/physiopathology* ; Mice, Inbred C57BL ; GABAergic Neurons/drug effects* ; Neural Inhibition/drug effects* ; Parvalbumins/metabolism* ; Neural Pathways/physiology* ; Cerebral Cortex/physiology*

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.