Objective: To explore the association between sleep quality and dry eye symptoms in adolescents,so as to provide the evidence for reducing the prevalence of dry eye symptoms. Methods: The study population was adolescents aged 12-24 years from the Psychology and Behavior Investigation of Chinese Residents (PBICR) survey, which was conducted from 20 June to 31 August 2022. A stratified random sampling and quota sampling method was used to select 6 456 adolescents within mainland China. The Ocular Surface Disease Index (OSDI) and Brief version of the Pittsburgh Sleep Quality Index (B-PSQI) were used to assess dry eye symptoms and sleep quality. Multiple Logistic regression model was used to explore the relationship between sleep quality and dry eye symptoms in adolescents. The influence of gender on the association was explored by using interaction terms. Results: A total of 2 815 adolescents reported having dry eye symptoms, with a prevalence of 43.6%. Logistic regression analysis results showed an increased risk of exacerbation of dry eye symptoms in adolescents with poor sleep quality. The OR (95% CI ) for mild, moderate, and severe dry eye symptoms groups were 1.39(1.16-1.67), 1.52(1.28-1.81), and 2.35(2.02-2.72), respectively, compared with the ocularly normal group ( P <0.05). There was a significant interaction between sleep quality and gender on dry eye symptoms in adolescents ( P <0.01). Conclusions Sleep quality is associated with dry eye symptoms in adolescents, and those with poor sleep quality have a higher risk of dry eye symptoms. The effect of sleep quality on dry eye symptoms is greater in boys.

ObjectiveTo understand the whole genome characteristics and the information for genetic evolution in the two coxsackievirus A2 (CVA2) strains isolated from patients with herpangina in Shanghai, and to provide a scientific basis for the prevention and treatment of herpetic angina. MethodsTwo CAV2 strains isolated from patients with herpetic angina in Shanghai were performed whole genome sequencing and analysis for phylogenetics, nucleotide homology, and evolution. ResultsA phylogenetic analysis of the VP1 region revealed that the two Shanghai strains both belonged to CVA2 genotype D, with the highest homology to OL357660, a strain from Yunnan. The average nucleotide identity (ANI) of the whole genome between the two Shanghai strains was 98.88%, and the ANI of the whole genome comparisons to other CVA2 genotype D strains and CVA2 genotypes A-C strains ranged from 84.64% to 97.42% and from 79.21% to 84.20%, respectively. The two Shanghai strains had low homology in the 3D region compared to the existing CVA2 strains. The phylogenetic analysis and sliding window nucleotide similarity analysis indicated that the two Shanghai strains and the Yunnan OL357660 strain might constitute a new genetic lineage. ConclusionThe two CVA2 strains isolated for the first time in Shanghai are assigned to genotype D (GenBank: PQ130039 and PQ130040), which is identical to the existing subtype prevalent in China. As represented by the Shanghai strains, a new CVA2 genetic lineage is been identified. This study has enriched the data on genetic evolution and genetic variation of CVA2 in Shanghai, indicating the requirement to strengthen surveillance for the epidemiological pattern of CVA2.

ObjectiveTo investigate the effect of video-based educational intervention combined with maternal presence on perioperative adverse outcomes in preschool children undergoing general anesthesia， including cooperation in anesthesia induction， perioperative anxiety， pain and agitation during recovery. MethodsA total of 300 preschool children scheduled for general anesthesia in our hospital from June to December 2023 were randomly assigned to control group （n=150） and intervention group （n=150）. The control group received routine recovery care. For the intervention group， in addition to routine recovery care， a preoperative visit was scheduled one day before surgery. During this visit， mothers were guided to watch anesthesia videos with their children. During the waiting period in the operating room and 30 minutes after awakening， the mothers were guided to accompany the children for more than 30 minutes. Recovery conditions were recorded using the surgical anesthesia information system， and the children’s anesthetic induction compliance， perioperative anxiety， pain， and agitation were evaluated and recorded using the modified Yale Preoperative Anxiety Scale （m-YPAS）， the Induction Compliance Scale （ICC）， the Children’s Pain Behavior Scale （FLACC）， and the Pediatric Agitation and Emergence Delirium Scale （PAED）. ResultsOn the preoperative visit day， there were no statistically significant differences in baseline data between the two groups （P > 0.05）. For perioperative anxiety， the m-YPAS scores of the intervention group were significantly lower than those of the control group， both when entering the operating room waiting area （35.27±6.48 vs. 41.79±6.68， P < 0.05） and 30 minutes after postoperative recovery （20.13±7.05 vs. 35.75±9.51， P < 0.05）. In terms of anesthesia induction cooperation， the ICC scores of the intervention group were significantly lower than those of the control group （1.84±0.95 vs. 3.17±0.62， P < 0.05）， and the proportion of good induction cooperation was significantly higher than that of the control group （24.00% vs. 12.67%， P < 0.05）. There was no significant difference in awakening duration between the two groups， but the intervention group had a significantly shorter length of stay in the post-anesthesia care unit than the control group （0.90±0.29 hours vs. 1.29±0.42 hours， P < 0.001）. For perioperative agitation， the PAED scores of the intervention group were significantly lower than those of the control group （entering in the operating room waiting area： 8.5 vs. 9.2， P < 0.05； 30 minutes after postoperative recovery： 4.2 vs. 7.8， P < 0.05）. In terms of pain scores， the FLACC scores of the intervention group were also significantly lower than those of the control group， both when entering the operating room waiting area （ 5.3 vs. 6.7， P < 0.05； 30 minutes after postoperative recovery： 2.1 vs. 4.9， P < 0.05）. ConclusionsVideo-based educational intervention combined with maternal presence reduces the perioperative anxiety， pain and agitation of preschool children undergoing general anesthesia， and improved the compliance of anesthesia induction. It is recommended to promote this intervention measure in clinical practice.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Huachansu (Cinobufacini) is active extract isolated from the dry skin of Bufo Bufo gargarizans. It has now been widely used in clinical treatment of cancer, this study is to clarify the material basis of down-regulation of thymidylate synthase (TYMS) induced by Huachansu. METHODS: Our study utilized UPLC-MS/MS to identify major bioactive components from Huachansu. Cell Counting Kit 8 (CCK-8) assay and clone formation assay were used to examine the cell viability of tumor cells. TYMS and γ-H2AX level were detected by using quantitative real-time RT-PCR and/or western blotting. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of TYMS could enhance the suppressive effect of Huachansu on cell growth of HCC cells. RESULTS: In our study, firstly, we identify 21 major bioactive components from Huachansu. CCK-8 assay results showed that Huachansu and its bioactive bufadienolides (Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin) significantly inhibited the proliferation of HepG2 and SK-HEP-1 cells in a dose- and time-dependent manner. Further molecular mechanistic investigation demonstrates that Huachansu significantly suppresses thymidylate synthase (TYMS), the enzyme which provides the sole de novo source of thymidylate for DNA synthesis. The inhibition of TYMS could lead to cell-cycle block and DNA damage of HCC cells. Furthermore, we identified that Huachansu markedly increased γ-H2AX expression, which indicated the presence of DNA damage. Moreover, we confirmed that transfection of cells with small interfering RNA specific to TYMS could increase the suppressive effects of Huachansu on the HCC cells proliferation. Quantitative RT-PCR analysis showed that Huachansu treatment had no effect on the transcription level of TYMS. Furthermore, proteasomal inhibitor MG132 could block TYMS inhibition induced by Huachansu, and concomitant administration of protein synthesis inhibitor cycloheximide (CHX) with Huachansu could further suppress the protein level of TYMS, indicating that Huachansu promotes proteasome-dependent degradation of TYMS in liver cancer cells. More importantly, the bioactive bufadienolides of Huachansu such as Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin could also significantly restrain the protein level of TYMS, revealing the material basis of inhibition of TYMS exposed to Huachansu. 5-Fluorouracil (5-FU) is a TYMS inhibitor, we also evaluate the effects of the combined treatment of Huachansu with 5-FU, the results show that interactions between Huachansu and 5-FU are synergistic or antagonistic. Thus, in clinical, attention should be paid to the dosage of Huachansu in combination with 5-FU. CONCLUSION Huachansu inhibits the growth and induces DNA damage of human HCC cells through proteasome-dependent degradation of TYMS, bioactive bufadienolides are the material basis of down-regulation of TYMS induced by Huachansu.

Luteolin is a natural flavonoid compound exists in various fruits and vegetables. Recent studies have indicated that luteolin has variety pharmacological effects, including a wide range of antidepressant properties. Here, we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power. Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin. Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets. The antidepressant effects of luteolin may involve promoting intracellular noradrenaline (NE) uptake; inhibiting 5-hydroxytryptamine (5-HT) reuptake; upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione S-transferase; and decreasing the expression of malondialdehyde, caspase-3, and amyloid-beta peptides. The antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic-pituitary-adrenal axis regulation, and 5-HT metabolism. Additionally, we identified insulin-like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor alpha (ESR1), and epidermal growth factor receptor (EGFR) as potential targets, luteolin has an ideal affinity for these targets, suggesting that it may play a positive role in depression through multiple targets, mechanisms, and pathways. However, the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.

Objective: To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments. Methods : The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains. Results : A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05). Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.

Objective:To explore influencing factors of poor prognosis in patients with severe trauma,and to analyze distribu-tion characteristics of adverse prognostic factors in patients with different early peripheral blood lymphocyte levels based on potential categories.Methods:A total of 174 patients with severe trauma treated in Mianyang Central Hospital from September 2020 to Septem-ber 2022 were selected.According to condition of massive blood transfusion or death within 24 hours after admission,patients were divided into:good prognosis group(n=136)and poor prognosis group(n=38).Clinical data of two groups were compared,multivariate Logistic regression analysis was used to analyze factors affecting poor prognosis,and cluster analysis and potential classification were used to analyze distribution characteristics of adverse prognostic factors in patients with different early peripheral blood lymphocyte levels.Results:Multivariate Logistic regression analysis results showed decrease of Glasgow coma scale(GCS),prolongation of acti-vated partial thromboplastin time(APTT),increase of D-dimer(D-D),decrease of fibrinogen(Fib),increase of fibrinogen degrada-tion products(FDP),increase of neutrophil/lymphocyte ratio(NLR)and decrease of lymphocyte level were factors influencing poor prognosis(P<0.05).Cluster analysis results showed that risk of poor prognosis was obviously clustered,and patients could be divided into poor prognosis high risk group(lymphocyte level≤0.90×109 L-1,n=72)and low risk group(lymphocyte level>0.90×109 L-1,n=102).Incidence of poor prognosis in high risk group[33.33%(24/72)]was significantly higher than that in low risk group[13.73%(14/102)](P<0.05).Potential category analysis results showed that there were three potential category distribution patterns in poor prognosis high risk group and low risk group.Proportion of"unelevated distribution of D-D in patients with low GCS score"in high risk group was significantly higher than that in low risk group,and proportion of"distribution of less risk factors"in high risk group was sig-nificantly lower than that in low risk group(P<0.05).There was no significant difference in proportion of elevated D-D distribution in patients with low GCS score between two groups(P>0.05).Conclusion:Decrease of GCS score,prolongation of APTT and increase of D-D are all associated with poor prognosis in patients with severe trauma.Patients with lymphocyte level≤0.90×109 L-1 have a higher risk of poor prognosis,and main influencing factors are"non-elevated distribution of D-D in patients with low GCS score".

Objective:To examine the impact of sleep quality on cognitive function in older adults with mild cognitive impairment(MCI)and explore the potential mediating role of depression.Methods:Using a cross-sectional design, we conducted an on-site questionnaire survey among 310 elderly individuals with MCI in Haishu District, Ningbo City from April to June 2021.Out of the 310 questionnaires collected, 299 were deemed valid.The survey encompassed gathering basic demographic information of the participants, as well as administering the Montreal Cognitive Assessment Scale, Patient Health Questionnaire Depression Scale, and Pittsburgh Sleep Quality Index Scale.Results:The cognitive functions of patients with MCI were found to be positively related to their education level( F=3.89, P<0.05).The correlation analysis indicated that sleep quality was positively correlated with depression( r=0.40, P<0.01)and negatively correlated with cognitive function( r=-0.22, P<0.01).Furthermore, a significant negative correlation was observed between depression and cognitive function( r=-0.20, P<0.01).The mediation analysis revealed that depression played a role in mediating the influence of sleep quality on cognitive function, with a mediation effect of -0.02(95% CI: -0.03--0.01). Conclusions:The cognitive function of elderly individuals with MCI can be significantly affected by sleep quality, with depression playing a mediating role.

Objective To explore the feasibility and rationality of advanced integrated two-stage laparoscopic simulation training course in standardized training of surgical residents.Methods From December 2019 to December 2021,the advanced integrated two-stage laparoscopic simulation training course was carried out among 2019-2020 surgical residents who received standardized training in our hospital.The course was divided into two stages.In the first stage,BEST(best essential surgical technology training)course,adopted Darwin? endoscopic training system,Tianyan? endoscopic training system,Microport? 3D laparoscopic training system and simple simulative models were used.The second stage,BEST PLUS course,same platform as that in BEST course and in vitro animal models were used.The questionnaire survey method(before and after class questionnaire)was adopted to evaluate the curriculum setting,such as curriculum form,simulators,teaching method,time arrangement,curriculum difficulty,training effect,curriculum satisfaction and so on.Results A total of 37 surgical residents completed the two-stage course training and the questionnaire survey.The overall satisfaction rate with the curriculum setting was 100%.There were 32 residents(86.5%)thought that first stage training course could significantly improve their clinical skills,35 residents(94.6%)thought that second stage training course could significantly improve their clinical skills,and 36 resident(97.3%)thought that the first stage curriculum could significantly help them improve performance in the second stage curriculum.Conclusions The trainees had a high degree of recognition and satisfaction for the advanced integrated two-stage laparoscopic simulation training course.The overall design of course was reasonable and feasible,and was attractive to trainees.

Objective To evaluate the effect of preoperative visits using virtual reality(VR)tech-nology on alleviating perioperative anxiety in children undergoing adenotonsillectomy for obstructive sleep ap-nea syndrome(OSAS).Methods Sixty children with OSAS scheduled for elective adenotonsillectomy were selected,including 32 males and 28 females,aged 6 to 12 years,ASA physical status Ⅰ or Ⅱ.The chil-dren were randomly divided into two groups using random number table:control group and VR group,30 children in each group.The control group received routine education and preoperative visits,while the VR group used VR smart glasses to play videos of three-dimensional scenes of the operating room in addition to routine visits.The modified Yale preoperative anxiety scale-short form(m-YPAS-SF)was used to assess perioperative anxiety levels.The heart rates(HR)of the children on the day before surgery,upon entering the preparation room,and immediately after anesthesia induction,and the induction compliance checklist(ICC)was used to evaluate anesthesia induction compliance,as well as the duration of stay in the recovery room and the length of hospital stay were recorded.Results Compared with control group,the m-YPAS-SF scores in VR group were significantly lower(P＜0.05),the HR was significantly lower upon entering the preparation room and immediately after anesthesia induction(P＜0.05),and the ICC scores were signifi-cantly lower(P＜0.05),recovery room stay duration and length of hospital stay were significantly short-ened(P＜0.05).Conclusion Preoperative visits using VR can effectively alleviate perioperative anxiety in children with OSAS undergoing adenotonsillectomy which can improve anesthesia compliance and reduce the length of hospital stay.