Objective: To understand the allocation and use of safety seats for preschool children and explore its related factors, so as to provide a scientific reference for promoting the usage of safety seats. Methods: A stratified random cluster sampling method was used to select 3 143 parents of preschool children aged 3 to 6 from six kindergartens in Shunyi District, Beijing from January 3 to 10, 2022. An online questionnaire survey was conducted to collect and evaluate the equipment and use of child safety seats in different characteristics of preschool children, as well as their scores of health beliefs. Multiple factor Logistic regression analysis was used to investigated the related factors of safety seat configuration and use. Results: The equipping rate and usage rate of safety seats for preschool children were 66.56% and 58.45%, respectively. The proportion of equipped and used safety seats for preschool children in core families (69.52%, 62.23%) were higher than that in large families (64.35%, 55.62%), only child families ( 72.39 %, 64.87%) were higher than non only child families (61.49%, 52.86%), and urban families (71.63%, 63.04%) were higher than rural families (52.31%, 45.51%) ( χ 2=9.23, 13.86; 41.72, 46.44; 101.96 ,76.97,all P <0.05) . As the educational level of parents ( χ 2 trend =154.23,98.76) and annual income of the family ( χ 2 trend =155.78,127.69) rised, the reporting rates of the equipped and used child safety seats in the family also increased(all P <0.05 ). There were statistically significant differences in the scores of different dimensions of health beliefs for the provision ( t =-20.22-18.16) and use ( t =24.32-24.17) of safety seats for preschool children(all P <0.05). After adjusting for child sex, child age, family annual income, parental education level, family type, whether the child was an only child, and place of residence，multivariate Logistic regression analysis showed that preschool children with higher perceived susceptibility score( OR =1.11, 1.08), higher self efficacy score( OR =1.23, 1.33), and higher suggestive factors score( OR =1.08, 1.12) were more likely to have and use safety seats in their families, while preschool children with higher perceived impairments score( OR =0.82, 0.80) were less likely to have and use safety seats in their families (all P <0.05). Conclusions The installation rate of child safety seats needs to be improved, and there is also a certain gap in their use after installation. Parents of preschool children should improve susceptibility and self efficacy to safety seat equipment and use, and perceptual barriers should be reduced.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Objective: To understand the current status and related factors of oral health behavior in preschool children, so as to provide scientific basis for improving parents oral health care abilities. Methods: From March 5 to 12, 2024, using a stratified cluster sampling method, an online questionnaire survey was conducted among parents of 1 381 preschool children aged 3-6 from 6 selected kindergartens of a district in Beijing. A structural equation model (SEM) was constructed based on the Theory of Planned Behavior framework to analyze the factors associated with preschool children s oral health behaviors. Results: The rates of parental assistance in brushing teeth, regular oral examination, and postprandial rinsing were 44.4%, 18.6% and 23.6%, respectively. Attitude, subjective norms were positively correlated with oral health behavior intention ( r =0.61, 0.55); attitude, perceived behavioral control, and behavioral intention were positively correlated with oral health behavior ( r =0.14, 0.13, 0.16) (all P < 0.01 ). The results of the SEM showed that attitude and subjective norms had a significant direct effect on oral health behavior intention ( β = 0.42 , 0.40), and the direct effect of perceived behavioral control on oral health behavior was statistically significant ( β =0.42) (all P <0.01). Conclusions The overall level of oral health behavior among preschool children needs to be improved. Perceived behavioral control is the most direct positive related factor of oral health behavior. In the future, intervention measures should focus on perceived behavioral control as the entry point and provide systematic intervention guidance in combination with planned behavior theory.

Objective To investigate the effect of programmed death receptor-1(PD-1)/pro-grammed death receptor-ligand-1(PD-L1)inhibitor combined with chemotherapy on gastrointestinal function and inflammatory markers in peripheral blood of patients with advanced gastric cancer(AGC).Methods The clinical data of 128 AGC patients treated in our hospital from February 2022 to August 2023 were retrospectively analyzed,and they were divided into control group(64 cases re-ceived conventional chemotherapy)and study group(64 cases received PD-1/PD-L1 inhibitor treat-ment+conventional chemotherapy)according to different treatment schemes.The short-term curative effect,gastrointestinal function level and inflammatory markers in peripheral blood before and after three cycles of treatment were recorded between the two groups,and the adverse reactions of the two groups were counted.Results The objective response rate(ORR)and disease control rate(DCR)in the study group were higher than those in the control group(P＜0.05).After three cycles of treatment,the levels of vasoactive intestinal peptide(VIP)and somatostatin(SS)decreased in both groups,while the levels of gastrin(GAS),motilin(MTL),and cholecystokinin(CCK)increased com-pared with those before treatment.The VIP and SS levels in the study group were lower than those in the control group,while the GAS,MTL,and CCK levels were higher(P＜0.05).After three cy-cles of treatment,the neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)decreased,and the lymphocyte-to-monocyte ratio(LMR)level increased in both groups compared with those before treatment.The NLR and PLR levels in the study group were lower than those in the control group,while the LMR level was higher(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the study group and the control group(P＞0.05).Conclusion PD-1/PD-L1 inhibitors combined with chemotherapy for AGC can improve short-term efficacy,enhance gastrointestinal function,reduce NLR and PLR levels in peripheral blood,increase LMR levels in peripheral blood,and do not increase adverse reactions.The combi-nation therapy is relatively safe.

Objective To investigate the molecular mechanism of aprepitant(Apr)reversing 5-Fluorouracil(5-FU)resistance in colorectal cancer(CRC)mouse model through endoplasmic re-ticulum stress(ERS).Methods Thirty mice were selected as experimental animals.Five mice were randomly assigned to control group,and the remaining 25 mice underwent subcutaneous injection in the back to establish the HCT-116/5-FU CRC mouse model.These mice were then divided into the CRC group,5-FU group,Apr group,Apr+5-FU group and Apr+ERS inhibitor Tauroursodeoxychol-ic acid(TUDCA)group,with five mice in each group.Changes in body weight and tumorigenesis in mice were recorded,and their organ indicators were calculated.Western blotting(WB)was used to detect the protein expression levels of protein kinase R-like ER kinase(PERK),eukaryotic initiation factor 2 subunit α(eIF2α),activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)in each group.Results At 5,10,15 and 20 d after medication,there were no statistically significant differences in body weight among CRC,5-FU,Apr,Apr+5-FU and Apr+TUDCA groups,neither in time points nor in interactions(P＞0.05).Two days after the last administration,there was no significant difference in the indexes of thymus,lung,liver,spleen,heart,kidney and other organs among all groups(P＞0.05).Compared with CRC group,the protein expression levels of PERK,P-EIF2α/eIF2α,ATF4 and CHOP in Apr group and Apr+5-FU group were significantly increased,the number of tumors was significantly decreased,the tumor mass was significantly de-creased,and the tumor volume was significantly decreased(P＜0.05),and the improvement of Apr+5-FU group was better than that of other groups(P＜0.05).Conclusion Apr can enhance chemotherapy sensitivity and reverse chemotherapy resistance in CRC mice,which may be mediated by downstream molecules of ERS pathway.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Exertional heatstroke is defined as a serious clinical syndrome typically characterized by impaired thermoregulation in high-temperature and high-humidity environments, resulting in heat production exceeding heat dissipation, causing core body temperature to exceed 40 centigrade, accompanied by central nervous system dysfunction and multi-organ failure. At present, the commonly used exertional heatstroke animal model is to put mice on a treadmill to run under high temperature and humidity conditions, but additional electrical stimulation is required to maintain the continuous running state of mice. However, additional electrical stimulation may lead to a further increase in mouse body temperature, which adversely affects the stability of the model. Therefore, medical staff from the intensive care unit of Xijing Hospital, Air Force Medical University, specially designed an intelligent experimental device for the exertional heatstroke model in mice, and obtained the national invention Patent of China (ZL 2022 1 1101721.2). The device integrates climate chamber, LCD touch screen and multiple sets of forced running wheel. Experimenters can observe and control the temperature, humidity, and wheel rotation parameters in the climate chamber in real time through a LCD touch screen. Each set of forced running wheel is equipped with a driving device that can be independently controlled. The device makes the mice run continuously without additional stimulation and enables the experimental personnel to observe and control the conditions in the climate chamber. The device successfully solves the problem of instability of the exertional heatstroke animal model and is convenient for the experimental personnel to control flexibly.
Animals ; Heat Stroke ; Mice ; Disease Models, Animal ; Hot Temperature ; Equipment Design ; Humidity ; Body Temperature