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.

Objective:To develop and validate a clinical prediction model for assessing the risk of postoperative pulmonary complications (PPCs) in elderly patients undergoing surgery with general anesthesia.Methods:This prospective observational study enrolled patients aged ≥65 years who underwent general anesthesia with mechanical ventilation duration >3 hours across six tertiary hospitals between December 2022 and August 2023. Based on follow-up outcomes (until discharge or postoperative day 7), patients were categorized into a non-PPCs group and a PPCs group. Detailed records included baseline patient characteristics, preoperative comorbidities, surgical information (type, duration), and bedside lung ultrasound scores (LUS) assessed within 24 hours postoperatively using a standardized 12-zone protocol. Predictor selection was performed using LASSO regression. Significant predictors identified were incorporated into a multivariate logistic regression analysis to build the prediction model, visualized as a nomogram. Internal validation was conducted via bootstrap resampling (1 000 repetitions). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) for discrimination, calibration curves for calibration accuracy, and decision curve analysis (DCA) for clinical utility.Results:A total of 130 eligible elderly surgical patients were included. PPCs occurred in 17 patients (incidence rate: 13.1%). Multivariate analysis identified LUS ( OR=1.248, 95% CI: 1.099-1.417, P=0.001) and elective surgery type ( OR=0.206, 95% CI: 0.043-0.988, P=0.048) as independent predictors of PPCs. The nomogram model demonstrated an AUC of 0.867 (95% CI: 0.775-0.959) upon initial testing. Internal validation confirmed good discrimination (AUC=0.863, 95% CI: 0.778-0.972). Calibration curves indicated excellent agreement between predicted probabilities and observed outcomes. Decision curve analysis demonstrated significant clinical net benefit across a wide range of threshold probabilities (0.03-0.89). Conclusions:The clinical prediction model, developed using early postoperative LUS scores and surgical type, effectively predicts the risk of postoperative pulmonary complications in elderly patients following surgery under general anesthesia. The model exhibits strong discrimination, calibration, and clinical utility, providing clinicians with a reliable tool for individualized risk assessment to support clinical decision-making and potentially reduce PPC incidence.

Objective To investigate the effect of intravenous lidocaine on postoperative fatigue syndrome(POFS)in patients undergoing laparoscopic resection for gastric carcinoma.Methods A total of 80 patients who underwent elective laparoscopic resection for gastric carcinoma at Xuzhou Central Hospital between September 2023 and June 2024 were enrolled.Inclusion criteria included age 18～75 years,ASA physical status classificationⅠ～Ⅲ,body mass index(BMI)of 18.5～27.9 kg/m2,preoperative Christensen score≤4,and estimated operation time≤4 hours.Patients were randomly allocated into either the lidocaine group(Group L)or the saline group(Group C)using a random number table,with 40 patients in each group.Group L received an intravenous infusion of lidocaine at a dose of 1.5 mg·kg?1 over 15 minutes,initiated 30 minutes before anesthesia induction.If no adverse reactions occurred,lidocaine was maintained at a rate of 1.5 mg/(kg·h)throughout the surgery until its conclusion.Group C received an equivalent volume of normal saline administered in the same manner.The Christensen score and Visual Analogue Scale(VAS)scores were recorded on postoperative days 1,3,5,and 7,and the time-weighted average(TWA)of the Christensen score was calculated.Postoperative inflammatory markers were measured,and additional outcomes including extubation time,post-anesthesia care unit(PACU)stay duration,postoperative nausea and vomiting(PONV),consumption of rescue analgesics,time to first flatus and defecation,and length of hospital stay were also documented.Results Compared with Group C,the TWA of the Christensen score in Group L decreased by 0.44 points(95％CI:0.11～0.76;P<0.05).The VAS scores were significantly lower in Group L on postoperative days 1 and 3(P<0.05).Levels of IL-6 and TNF-α at the end of surgery and 24 hours after surgery were also lower in Group L(P<0.05).The time to first flatus and defecation was significantly shorter in Group L(P<0.05).There were no significant differences between the two groups regarding extubation time,PACU stay duration,incidence of PONV,postoperative consumption of remedial analgesic drugs,or length of hospital stay(P>0.05).Conclusion Intravenous lidocaine may improve POFS in patients following laparo-scopic resection for gastric carcinoma by attenuating inflammatory responses,alleviating pain,and facilitating gastrointestinal function recovery,while maintaining a favorable safety profile.

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

When the epidemiology of infectious diseases is more complex, it is often difficult for disease prediction studies based on a single model to capture the multidimensional nature of disease transmission. In recent years, combining different models to improve infectious disease prediction has gradually become a research trend and hotspot. Existing studies have shown that combined models usually have higher prediction performance and better generalization ability. The current combined models mainly combine machine learning and other models, including time-series models, dynamic models, etcetera. In addition, integrated learning that combines diverse machine learning techniques also holds significant importance across various research domains. This paper reviews the progress of applying combined models around machine learning in infectious disease prediction to promote the innovation and practice of combined models for infectious diseases and help to build smarter and more efficient infectious disease early warning and prediction methods and systems.

Methods such as compartmental models, agent-based models, time series models, and machine learning can be used for the prediction of infectious disease incidence. When disease epidemics are complex, it is often difficult to use a single model to comprehensively and accurately capture the multi dimensional nature of the disease. Exploring the combined application of different models has gradually become a research trend and hotspot in recent years, and the prediction performance of combined models is often better than that of single ones. Current research related to combined models mainly focus on machine learning or compartmental models. In this review, we focus on the combination of compartmental models and other models, and summarize their combination principles, application progress, and advantages or disadvantages for the purpose of promoting the innovation and application of combined models for infectious disease incidence prediction, and establishing a more intelligent and efficient early warning and prediction method or systems for the prevention and control of infectious disease.