ObjectiveTo investigate the role and mechanism of Lck/Yes-related novel protein tyrosine kinase （Lyn） on lipopolysaccharide （LPS）-induced M1-type polarization of macrophage. MethodsThe LentiCRISPR-V2 plasmid was digested with the restriction endonuclease BSMBI-V2， and the digested DNA fragments were recovered. The digested plasmid was ligated with Lyn-sgRNA using T4 ligase to generate the Lenti-Lyn-gRNA lentivirus. THP-1 cells were infected with the Lenti-Lyn-gRNA lentivirus to obtain a stable cell line with Lyn knockout， and a monoclonal THP-1 cell line with complete Lyn knockout （Lyn^⁻/⁻） was established subsequently. Wild-type Lyn （Lyn^WT） and Lyn^⁻/⁻ THP-1 cells were induced with 100 ng/mL phorbol myristate acetate （PMA） for 48 h to differentiate into M0 macrophages， which were further polarized into M1 macrophages by stimulation with 100 ng/mL LPS for 24 h. Quantitative real-time polymerase chain reaction （qPCR） was performed to detect the expression of M0 macrophage markers， including integrin αM （CD11b）， macrophage antigen （CD68）， and monocyte differentiation antigen （CD14）. The expression of Lyn in M1 macrophages differentiated from wild-type THP-1 cells （Lyn^WT-M1） was measured by qPCR， and the ratio of phosphorylated Lyn to total Lyn （P-Lyn/Lyn） in Lyn^WT-M1 cells was determined by Western blot. In M1 macrophages differentiated from Lyn-knockout THP-1 cells （Lyn^⁻/⁻-M1）， qPCR was used to detect the mRNA expression of inducible nitric oxide synthase （iNOS）， interleukin-6 （IL-6）， and chemokine （C-X-C motif） ligand 10 （CXCL-10）. Western blot was conducted to assess the protein expression of iNOS， as well as the protein levels of molecules related to the Janus kinase 1 （JAK1）-signal transducer and activator of transcription 1 （STAT1）signaling pathway， including JAK1， phosphorylated JAK1 （P-JAK1）， STAT1， and phosphorylated STAT1 （P-STAT1）. Additionally， the expression of the M1 macrophage marker cluster of differentiation 80 （CD80） was analyzed by flow cytometry. ResultsThe Lyn^-/- monoclonal cell line was successfully constructed. The expression of CD11b was significantly elevated in Lyn^-/- M0 macrophages， and the differentiation of M1 macrophages was successful. Knockdown of Lyn inhibited mRNA expression of iNOS， IL⁃6， CXCL⁃10， protein expression of iNOS and CD80 expression in M1 macrophages （P<0.05）. Western blot assay showed that Lyn knockdown inhibited protein expression of JAK1 and P-STAT1 （P<0.01）. ConclusionAfter CRISPR/Cas9-mediated Lyn knockout， the expression levels of JAK1 and P-STAT1， the key molecules in the JAK/STAT signaling pathway of M1 macrophages， are significantly downregulated； concomitantly， the expression of M1 macrophage-specific secretory factors （iNOS， IL⁃6， CXCL⁃10 mRNA） and CD80 is also downregulated， which may be achieved via targeted regulation of the JAK1/P-STAT1-mediated JAK/STAT signaling pathway.

OBJECTIVE To formulate the Hazardous Drug List in China， and provide a scientific basis for standardizing the management of hazardous drugs， preventing and controlling occupational exposure risks in medical institutions at all levels in China. METHODS Under the joint organization of the Intravenous Medication Admixture Management Professional Committee of the Chinese Pharmaceutical Association and the National Medical Quality Control Center for Pharmaceutical Management， based on literature research and international hazardous drug lists and their development procedures， the scope of hazardous drug selection， selection principles， and evidence confirmation criteria were determined through expert panel seminars and expert questionnaire survey method （Delphi method）. Chemical drugs， biological agents， and Chinese patent medicines marketed in China that met the selecti on principles were screened to form the Chinese Expert Consensus on the Hazardous Drug List . RESULTS Five principles for selecting hazardous drugs were established （including protective labeling in package inserts， carcinogenicity， reproductive toxicity， genotoxicity， and organ toxicity at low doses）， along with the corresponding evidence confirmation criteria. The Hazardous Drug List containing 210 drugs was formulated， covering anti-tumor drugs， endocrine system drugs， nervous system drugs， immunomodulators， anti-infective drugs， cardiovascular system drugs， hematological system drugs， urinary system drugs， obstetrics and gynecology drugs， dermatological drugs and other categories. Compared with international hazardous drug lists， 25 newly included hazardous drugs were added， including 15 anti-tumor drugs， 6 Chinese patent medicines and 4 biological agents. In addition， 88 Chinese patent medicines that may have potential occupational exposure risks are listed in the appendix for reference by medical institutions in management. CONCLUSIONS The development of this consensus closely aligns with the actual clinical drug use in China， with a scientific and rigorous methodology， and can serve as a reference for medical institutions at all levels to standardize the management of hazardous drugs and prevent and control occupational exposure risks.

The core pathological process of optic neuropathy caused by glaucoma is the progressive loss of retinal ganglion cells(RGCs). As the primary glial cells in the retina, Müller glial cells play a crucial and complex dual regulatory role in the pathological microenvironment of glaucoma. On one hand, Müller cells can exert endogenous protective effects by secreting neurotrophic factors, enhancing RGC viability through co-culture, and regulating glutamate metabolism. On the other hand, under sustained stress such as elevated intraocular pressure, Müller cells are activated by mechanosensitive channels(e.g., TRPV4), transforming into a reactive gliosis phenotype. This leads to the release of inflammatory cytokines that exacerbate RGC apoptosis, while their metabolic reprogramming and epigenetic alterations also contribute to the process of neuronal injury. This article systematically reviews the research progress on the dual roles of Müller cells in protecting and damaging the optic nerve in glaucoma, exploring new therapeutic strategies for neuroprotection by regulating their cellular states. It outlines the main controversies and unresolved issues in this field and, based on the latest research advances, analyzes the implications of targeting Müller cells for current clinical treatments and future development trends.

ObjectiveTo investigate whether photoreceptor-specific knockout of lanosterol synthase （Lss） induces age-related retinal degeneration and to elucidate the underlying molecular mechanisms. MethodsPhotoreceptor-specific Lss knockout mice （Lss^flox/flox； Rho-Cre， CKO） models were established. Retinal structure and function were assessed at 1， 4， and 8 months of age using fundus photography， optical coherence tomography （OCT）， scotopic electroretinogram （ERG） and hematoxylin and eosin （HE） staining. The mouse photoreceptor cell line 661W served as an in vitro model. Lss was knocked down via siRNA， followed by analyses including Seahorse XF mitochondrial stress test， JC-1， MitoSOX Red and DCFH-DA probes to evaluate mitochondrial function and oxidative stress， glycolytic rate assay for glycolysis ability， RT-qPCR for inflammatory factors， γH2AX immunofluorescence for double-strand DNA damage detection， and transcriptome sequencing to identify differentially expressed genes and enriched pathways. ResultsCompared with controls， 1-month-old CKO mice showed no abnormalities. Mild fundus lesions appeared at 4 months. By 8 months， CKO mice exhibited significant thinning of the outer nuclear layer， disorganization of the inner/outer segment structure， and markedly reduced amplitudes of the dark-adapted ERG a- and b-waves （P<0.05）. Transcriptome analysis revealed 1 842 differentially expressed genes （826 up-regulated， 1 016 down-regulated）， with Lss being the most significantly downregulated gene； these genes significantly enriched in sterol biosynthesis， oxidative phosphorylation， aerobic electron transport chain， and ATP synthesis （P<0.05）. In 661W cells， knockdown of Lss significantly reduced mitochondrial basal respiration （P=0.006）， ATP production （P=0.015）， maximal respiration （P<0.001）， and spare respiratory capacity （P<0.001）， while basal glycolysis （P=0.005） and compensatory glycolysis （P=0.028） were increased. These changes were accompanied by mitochondrial membrane potential depolarization （P<0.001）， elevated mitochondrial reactive oxygen species （ROS） levels （P<0.001）， and increased total ROS levels （P=0.013）. Additionally， the mRNA expression of inflammatory factors， including Ccl2 （P=0.004）， Ccl5 （P=0.012）， Cxcl1 （P<0.001）， Cxcl5 （P<0.000 1）， Tgfb （P=0.008）， Hgf （P<0.000 1） and Mmp3 （P=0.003） was significantly upregulated. Moreover， γH2AX fluorescence intensity was increased （P=0.002）. ConclusionsPhotoreceptor-specific Lss deficiency induces mitochondrial dysfunction， oxidative stress and cellular inflammation， ultimately leading to age-dependent retinal degeneration. This study provides novel mechanistic insights and potential therapeutic targets for hereditary and age-related retinal degenerative diseases.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective: To analyze respiratory syncytial virus(RSV) outbreaks surveillance results and the epidemiological characteristics in kindergarten and school in Shenzhen during 2017-2023 , so as to provide a scientific reference for control and prevention of RSV. Methods: Epidemiological data and surveillance results of RSV outbreaks in kindergarten and school from 2017 to 2023 were collected for descriptive analyses. Results: A total of 31 RSV outbreaks were identified in kindergarten and school in 2017-2023 in Shenzhen, 346 cases were reported, the average incidence rate was 22.02%. The most annual RSV outbreaks were reported in 2020 with 14 outbreaks, followed by 8 outbreaks in 2023. A total of 64.52% of RSV outbreaks were identified in kindergarten with rest occurring in primary school or middle school. The greatest monthly count of outbreak was 18 (58.06%) in September, followed by 3 outbreaks (9.68%) in March and October. A total of 244 swab samples were collected, 169 samples were positive for respiratory viruses, the positive rate was 69.26%, 121 samples were positive for RSV,from 31 respiratory syncytical virus outbreaks 57 and samples were positive for other respiratory viruses(9 samples were positive for two respiratory viruses). A toral of 14(45.16%) outbreaks are caused by RSV alone, 17 outbreaks (54.84%) were caused by RSV and other respiratory viruses. Conclusions Most RSV outbreaks in kindergarten and school are reported after 2020 in Shenzhen, most RSV outbreaks occur in kindergarten, peak seasons of RSV outbreaks are autumn and spring.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.