Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective: To investigate the relationship between night-time noise exposure and depressive symptoms among junior and senior high school students, so as to provide evidence to support strategies for promoting their physical and mental health. Methods: From September 2024 to December 2025, 2 900 junior and senior high school students were selected using stratified cluster random sampling in the three cities of Nanning, Lhasa, and Yanji. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms in junior and senior high school students, and a noise exposure survey was conducted. Chi-square test was used to compare the prevalence of depressive symptoms among junior and senior high school students with different types of night-time noise exposure, and Logistic regression models were employed to examine the association between night-time noise exposure and depressive symptoms among junior and senior high school students. Results: The prevalence of depressive symptoms among junior and senior high school students without night-time noise exposure was 33.0%, while that among junior and senior high school students with night-time noise exposure was 49.0%; the difference was statistically significant ( χ 2= 45.85 , P <0.01) . After adjusting for gender, age and region, Logistic regression analysis showed that exposure to night-time traffic noise, neighborhood noise, air conditioner noise, and other types of noise showed increased risk of detecting depressive symptoms in junior and senior high school students ( OR =2.22, 1.84, 2.41, 2.17, all P <0.05). Conclusion Night-time noise exposure is associated with an increased risk of depressive symptoms among junior and senior high school students.

Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.

Objective: To explore the distribution of traditional Chinese medicine (TCM) syndromes in children with hepatolenticular degeneration (Wilson disease, WD) based on factor analysis and cluster analysis. Methods: From November 2018 to November 2023, general information (gender, age of admission, age of onset, course of disease, clinical staging, Western medicine clinical symptoms, and family history) and TCM four-examination informations (symptoms and signs) were retrospectively collected from 757 cases of children with WD at the First Affiliated Hospital of Anhui University of Chinese Medicine, and factor analysis and cluster analysis were used to investigate TCM syndromes in children with WD. Results: A total of 757 children with WD were included, of which 483 were male and 274 were female; the median age at admission was 12.58 years, the median age at onset was 8.33 years, and the median course of disease was 24.37 months; clinical typing result indicated 506 cases of hepatic type, 133 cases of brain type, 99 cases of mixed-type, and 19 cases of other type; 36.46% of the children had no clinical symptoms (elevated aminotransferases or abnormalities in copper biochemistry); a total of 177 cases had a definite family history, and 10 cases had a suspected family history. Forty-three TCM four-examination information were obtained, with the top 10 in descending order being feeling listless and weak, brown urine, slow action, inappetence, dim complexion, slurred speech, angular salivation, body weight loss, hand and foot tremors, and abdominal fullness. In children with WD, the syndrome element of disease location was primarily characterized by the liver, involving the spleen and kidney, and the syndrome elements of disease nature were characterized by dampness, heat, and yin deficiency. Based on factor analysis and cluster analysis, five TCM syndromes were derived, which were, in order, syndrome of dampness-heat accumulation (265 cases, 35.01%), syndrome of yin deficiency of the liver and kidney (202 cases, 26.68%), syndrome of liver hyperactivity with spleen deficiency (185 cases, 24.44%), syndrome of qi and blood deficiency (79 cases, 10.44%), and syndrome of yang deficiency of the spleen and kidney (26 cases, 3.43%). Conclusion The TCM syndromes of children with WD were primarily syndromes of dampness-heat accumulation, yin deficiency of the liver and kidney, and liver hyperactivity with spleen deficiency. The liver was the main disease location, and the disease nature was characterized by deficiency in origin and excess in superficiality, excess and deficiency mixed. These findings suggest that treating children with WD should be based on the liver while also considering the spleen and kidney.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.

ObjectiveTo study the correlations between traditional Chinese medicine （TCM） syndromes and lipid metabolism in children with Wilson disease （WD）. MethodsClinical data and lipid metabolism indicators ［total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， apolipoprotein A1 （ApoA1）， apolipoprotein B （ApoB）， and lipoprotein a （Lpa）］ were retrospectively collected from 341 children with WD. The clinical data were compared among WD children with different syndromes， and the correlations between TCM syndromes and lipid metabolism in children with WD were analyzed. Least absolute shrinkage and selection operator （LASSO） regression was used for variable screening， and unordered multinomial Logistic regression was employed to analyze the effects of lipid metabolism indicators on TCM syndromes. ResultsThe 341 children with WD included 121 （35.5%） children with the dampness-heat accumulation syndrome， 103 （30.2%） children with the liver-kidney Yin deficiency syndrome， 68 children with the combined phlegm and stasis syndrome， 29 children with the spleen-kidney Yang deficiency syndrome， and 20 children with the liver qi stagnation syndrome. The liver-kidney Yin deficiency syndrome， combined phlegm and stasis syndrome， and spleen-kidney Yang deficiency syndrome had correlations with the levels of lipid metabolism indicators （P<0.05）. Lipid metabolism abnormalities occurred in 232 （68.0%） children， including hypertriglyceridemia （108）， hypercholesterolemia （23）， mixed hyperlipidemia （67）， lipoprotein a-hyperlipoproteinemia （12）， and hypo-HDL-cholesterolemia （22）. The percentages of hypertriglyceridemia and hypo-HDL-cholesterolemia varied among children with different TCM syndromes （P<0.05）. Correlations existed for the liver-kidney Yin deficiency syndrome with TG， TC， and HDL-C， the combined phlegm and stasis syndrome with TG， the spleen-kidney Yang deficiency syndrome with TG， TC， and LDL-C， and the liver Qi stagnation syndrome with TC and LDL-C （P<0.05， P<0.01）. ConclusionThe TCM syndromes of children with WD are dominated by the dampness-heat accumulation syndrome and the liver-kidney Yin deficiency syndrome， and dyslipidemia in the children with WD is dominated by hypertriglyceridemia and mixed hyperlipidemia. There are different correlations between TCM syndromes and lipid metabolism indicators， among which TG， TC， LDL-C， and HDL-C could assist in identifying TCM syndromes in children with WD.

Objective To explore the correlation between pre-pregnancy body mass index (BMI) and the risk of difficult airway during labor and delivery through grading changes of Mallampati test (MT). Methods A total of 354 primiparous women who delivered at Obstetrics and Gynecology Hospital of Fudan University from October 2020 to April 2021 were enrolled and categorized into low BMI, normal BMI, and high BMI groups based on pre-pregnancy BMI. Changes in MT grading were analyzed during early labor, postpartum (20 minutes to 1 hour after placental delivery), and 48 hours postpartum. A multifactor logistic regression model was used to analyze the factors increased MT grading postpartum. Results Among the 354 participants, 97 (27.4%) exhibited increased MT grading postpartum, with the proportion of women classified as MT grade 3-4 rising from 39 (11.0%) during early labor to 77 (21.8%) postpartum. By 48 hours postpartum, the number of women with MT grade 3-4 decreased to 21 (5.9%). Multifactor logistic regression analysis showed that low pre-pregnancy BMI (vs high BMI: OR＝2.15, 95%CI 1.02-4.53, P＝0.045) and snoring history during pregnancy (OR＝2.32, 95% CI 1.38-3.90, P＝0.001) were independent risk factors for postpartum MT grading elevation. Conclusions MT grading might increase postpartum in parturients, with low pre-pregnancy BMI and prenatal snoring history identified as significant risk factors for elevated MT grading after delivery.