Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

OBJECTIVE To investigate the mechanism of Bushen huoxue formula in improving pregnancy outcomes in mice with antiphospholipid antibody-related recurrent spontaneous abortion （aPL-RSA）. METHODS SPF female BALB/c mice were randomly divided into normal control group， adjuvant control group， model group， and Bushen huoxue formula group. The aPL-RSA mouse model was established by immunization with β 2 glycoproteinⅠcombined with Freund’s adjuvant. From gestational day 0， the Bushen huoxue formula group was administered 1.653 6 g/（kg·d） of the prescription by gavage， while the other three groups received an equal volume of normal saline， twice daily for 15 consecutive days. The uterine appearance of pregnant mice was observed； individual embryo weight was recorded， and the embryo resorption rate was calculated. The proportion of activated CD41 + CD62p + platelets in platelet-rich plasma （PRP） was detected. Serum levels of thromboxane B2 （TXB2） and platelet factor 4 （PF4） were measured. Morphological changes of placental tissue were observed. The cell apoptosis rate of placental tissue was detected. The levels of malondialdehyde （MDA） content， tot al superoxide dismutase （T-SOD） activity， the interleukin-1β （IL-1β） and IL-18， the protein expressions of matrix metalloproteinase-3 （MMP-3）， MMP-9， nuclear proliferation antigen-67 （Ki67）， superoxide dismutase 2 （SOD2）， Nod-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and caspase-1， as well as the mRNA expressions of superoxide dismutase 2（SOD2）， NLRP3， ASC and caspase-1 of placental tissue were detected. RESULTS Compared with the normal control group and adjuvant control group， the model group showed significant decreases in individual embryo weight， T-SOD activity of placental tissue， and relative expression levels of SOD2 mRNA and protein （ P ＜0.05）； while significant increases were observed in embryo resorption rate， proportion of activated CD41 + CD62p + platelets in PRP， serum levels of TXB2 and PF4， placental cell apoptosis rate， MDA content in placental tissue， relative protein expressions of MMP-3， MMP-9 and Ki67， relative protein and mRNA expression levels of NLRP3， ASC and caspase-1 as well as IL-1β and IL-18 levels （ P ＜0.05）. The model group also exhibited irregular uterine morphology with localized atrophy in some uterine horns； placental tissue showed fragmentation of decidual cells， extensive vacuolization and necrosis of trophoblast cells in the labyrinthine zone， accompanied by vascular reduction. After intervention with Bushen huoxue formula， the above indicators were significantly reversed （ P ＜0.05）， and uterine morphology and pathological damage were markedly improved. CONCLUSIONS Bushen huoxue formula can effectively improve pregnancy outcomes in aPL-RSA model mice， and its mechanism may be closely related to inhibiting platelet activation， reducing oxidative stress injury， enhancing trophoblast cell function， and suppressing the inflammatory response mediated by the NLRP3 inflammasome pathway.

OBJECTIVES: Urinary calculi are characterized by a high recurrence rate, and patients' adherence to self-management after discharge directly affects health outcomes. Traditional offline follow-up models often face problems such as poor compliance and uneven allocation of medical resources, making it difficult to meet individualized health management needs. Remote follow-up provides a novel solution to optimize long-term management, improve health literacy, and enhance clinical outcomes. This study aims to evaluate the effect of remote follow-up under an intelligent medical collaborative model on quality of life and health-promoting lifestyle in patients with urinary calculi, and to assess its short-term impact on clinical outcomes. METHODS: A total of 118 patients with urinary calculi admitted to a tertiary hospital in Hunan Province between August and November 2024 were recruited and randomly assigned to a control group (n=59) or an intervention group (n=59). The control group received routine departmental follow-up, while the intervention group underwent remote follow-up based on an intelligent medical collaborative model for one month. Assessments were conducted before discharge (T0), 15 days after discharge (T1), and one month after discharge (T2), using the Wisconsin Stone Quality of Life Questionnaire and the Health-Promoting Lifestyle Profile. At T2, the incidence of forgotten ureteral stents (FUS), ureteral stent-related complications, unplanned readmissions, and patient satisfaction were evaluated. RESULTS: No significant differences were observed between groups at T0 in baseline characteristics or outcome measures (all P>0.05). At T1 and T2, the intervention group had significantly higher health-related quality of life scores than the control group (P<0.05). Generalized estimating equation (GEE) analysis showed significant between-group effects (Wald's χ²=22.961, P<0.001), time effects (Wald's χ²=23.065, P<0.001), and interaction effects (Wald's χ²=6.930, P<0.05). Similarly, at T1 and T2, the intervention group scored significantly higher on health-promoting lifestyle than the control group (P<0.05), with significant between-group effects (Wald's χ²=22.936, P<0.001), time effects (Wald's χ²=10.694, P<0.001), and interaction effects (Wald's χ²=18.921, P<0.05). No significant differences were found between groups in the incidence of FUS, ureteral stent-related complications, or unplanned readmissions (all P>0.05). Patient satisfaction was significantly higher in the intervention group (t=4.089, P<0.001). CONCLUSIONS Remote follow-up under an intelligent medical collaborative model helps improve quality of life, promote health-oriented lifestyles, and enhance patient satisfaction among individuals with urinary calculi.
Humans ; Quality of Life ; Male ; Female ; Urinary Calculi/therapy* ; Health Promotion/methods* ; Middle Aged ; Adult ; Follow-Up Studies ; Treatment Outcome

Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
RNA, Long Noncoding/physiology* ; Osteogenesis/physiology* ; Humans ; Neovascularization, Physiologic/genetics* ; Bone and Bones/metabolism* ; Animals ; Mesenchymal Stem Cells ; Signal Transduction ; Osteoblasts ; Osteoclasts ; Angiogenesis

The identification and optimization of mutations in nanobodies are crucial for enhancing their therapeutic potential in disease prevention and control. However, this process is often complex and time-consuming, which limit its widespread application in practice. In this study, we developed a workflow, named Evolutionary-Nanobody (EvoNB), to predict key mutation sites of nanobodies by combining protein language models (PLMs) and molecular dynamic (MD) simulations. By fine-tuning the ESM2 model on a large-scale nanobody dataset, the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced. The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies. Additionally, we selected four widely representative nanobody-antigen complexes to verify the predicted effects of mutations. MD simulations analyzed the energy changes caused by these mutations to predict their impact on binding affinity to the targets. The results showed that multiple mutations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target, further validating the potential of this workflow for designing and optimizing nanobody mutations. Additionally, sequence-based predictions are generally less dependent on structural absence, allowing them to be more easily integrated with tools for structural predictions, such as AlphaFold 3. Through mutation prediction and systematic analysis of key sites, we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes. The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Objective To put forward relevant national legislative proposals for preventing workplace violence (WPV) in the healthcare industry by comparing the current legal practices of China and the United States. Methods The Workplace Violence Prevention for Health Care and Social Service Workers Act (hereinafter referred to as the "Act") of the United States was translated and analyzed. The relevant normative legal documents in China were systematically reviewed to compare the legislative differences in the prevention and control of WPV against health care workers. Results The Act aims to establish an employer-driven legal framework for WPV prevention and control. China has no specific legislation for WPV, but has established partial legislation for protecting healthcare workers from external violence through various legal practices. The "Act" regards WPV as an occupational hazard and adopts the priority control order to carry out the prevention and control of WPV. In contrast, China's legislation for WPV approach emphasizes public security and undermines occupational health, treating WPV merely as a work-related injury or accident with limited protection. This gap reveals divergent priorities for legal interests. Conclusion China should integrate WPV prevention and control into the occupational health legal framework through revising existing laws, advancing dedicated legislation, and ratifying relevant international conventions, to strengthen the occupational health legal system. All stakeholders should clarify the responsibilities for WPV prevention and control of healthcare workers, and ensure comprehensive legislative response.

Objective:To explore the relationship between thyroid hormone sensitivity and metabolic dysfunction-associated steatotic liver disease(MASLD) in a population with normal thyroid function, with a particular focus on sex-specific differences.Methods:This retrospective study included 41 355 euthyroid cases who underwent routine health examinations at the Health Management Centre of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2023 were included. The free triiodothyronine(FT 3) to free thyroxine(FT 4) ratio(FT 3/FT 4) was calculated in order to reflect the peripheral sensitivity of the thyroid gland. Similarly, thyroid feedback quantile-based index(TFQI), thyrotrophic thyroxine resistance index(TT 4RI), and the FT 3-based TFQI-derived index(TFQI-FT 3) were calculated in order to reflect the central sensitivity of the thyroid gland. A Logistic regression was employed to analyse the effect of sex-specific thyroid hormone sensitivity indices on the prevalence of MASLD. The restricted cubic spline was used to analyse the non-linear relationship between the thyroid sensitivity hormone indices and MASLD. Furthermore, the correlation between the thyroid hormone sensitivity indices and MASLD in different subgroups was also analysed. Results:The prevalence of MASLD in the study population was 28.8%. After adjusting the model for confounders, the risk of MASLD increased by 7%, 3%, 10%, and 5% for each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in the total population, respectively. The risk of MASLD increased by 6% and 5% for each standard deviation increase in FT 3/FT 4 and TFQI-FT 3 in men, respectively. For each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in women, the risk of MASLD increased by 6%, 5%, 11%, and 5%, respectively. Higher FT 3/FT 4 and TFQI-FT 3 were positively associated with the risk of developing MASLD in men, and higher FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI were positively associated with the risk of developing MASLD in women. There was a non-linear, inverted U-shaped relationship between TFQI and risk of MASLD in women. Subgroup analyses showed positive associations between FT 3/FT 4, TFQI, TFQI-FT 3, and MASLD. Conclusions:The thyroid hormone sensitivity indices may provide a basis for clinical prevention and management of MASLD in individuals with normal thyroid function. Additionally, FT 3/FT 4 and TFQI-FT 3 may indicate the risk of MASLD in the general population, while TFQI and TT 4RI are more suitable for assessing the risk of MASLD in women.

Objective:To analyze the risk factors for human cytomegalovirus (HCMV) infection in pediatric recipients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of children who underwent first allo-HSCT were retrospectively analyzed from March 2017 to November 2024. A total of 259 pediatric allo-HSCT recipients were analyzed through comparing HCMV infection group (n=115) and Non-HCMV infection group (n=144). Clinical characteristics were compared, and risk factors for HCMV infection were analyzed using univariate and multivariate logistic regression.Results:The result of univariate analysis showed that adrenoleukodystrophy (ALD), length of hospitalization, duration of antiviral therapy, and bacterial infection were significantly associated with HCMV infection in pediatric allo-HSCT recipients ( P<0.05). The result of multivariate analysis showed that ALD was an independent protective factor against HCMV infection of allo-HSCT recipients ( P<0.05) [OR=0.22, 95% CI: 0.06-0.86], while umbilical cord blood transplantation (UCBT) was an independent risk factor for HCMV infection in allo-HSCT recipients ( P<0.05) [OR=6.13, 95% CI: 1.34-28.04]. When the area under the ROC curve (AUC) for predicting post-transplant relapse based on HCMV viral load was 0.75 (95% CI: 0.55-0.94, P=0.014) and at the cutoff value of 3×10 3 copies/ml, the sensitivity and specificity for predicting relapse were 81.13% and 66.67%, respectively. Conclusions:HCMV infection in pediatric allo-HSCT recipients may lead to longer hospitalization and increased risk of relapse.