Objective To explore the mechanism by which breast cancer-derived LncRNA OIP5-AS1 regulates the migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the M2 polarization of tumor-associated macrophages (TAM). Methods MDA-MB-231 cells were divided into the control group (blank control), the NC group (transfected with NC siRNA), and the si-OIP5 group (transfected with LncRNA OIP5-AS1 siRNA). The mRNA expression levels of LncRNAs OIP5-AS1, IL-4, and IL-13 were detected by RT-qPCR. The protein expression levels of IL-4 and IL-13 in the culture supernatant were detected by ELISA. The culture supernatant from the control group was added to RPMI 1640 medium at different volume ratios to induce the polarization of M0 macrophages into TAMs. The mRNA expression of CD206 in TAMs was detected by RT-qPCR. M0-type macrophages were induced with the medium supernatant of the NC group/si-OIP5 group, and the expression of CD206 was detected by Western blot. Subsequently, a co-culture model of macrophage and MDA-MB-231 was constructed to evaluate the migration and invasion abilities of MDA-MB-231 cells and detect the expression changes in Vimentin, N-cadherin and E-cadherin. Results Compared with the control and NC groups, the si-OIP5 group showed significantly downregulated expression of LncRNA OIP5-AS1 (P<0.001) and significantly decreased IL-13 mRNA and protein levels (P<0.05). Meanwhile, no significant difference was observed in the expression of IL-4 among the groups. Conditioned medium induced CD206 expression in M0 macrophages in a volume-dependent manner, with the strongest effect at a 40% volume ratio (P<0.001). The CD206 protein level in the si-OIP5 group significantly decreased (P<0.01). In the co-culture system, the migration and invasion abilities of MDA-MB-231 cells in the si-OIP5 group significantly weakened (P<0.001), the expression of E-cadherin was upregulated, and the expression levels of N-cadherin and Vimentin were downregulated (both P<0.01). Conclusion Breast cancer-derived LncRNA OIP5-AS1 can induce TAM M2 polarization mediated by IL-13, thereby promoting the migration, invasion, and EMT of breast cancer cells.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Liver cancer (LC) remains one of the most prevalent tumors globally. Despite considerable advancements in its clinical treatment in recent years, the global burden of this disease is projected to increase. According to World Health Organization statistics, the number of LC deaths worldwide in 2022 was 760,000, ranking third among all cancers. Therefore, there is an urgent need to delve deeper into the realms of LC diagnosis, prognosis, and treatment. Proteomics, as an emerging technology leveraging mass spectrometry (MS)-based protein identification, liquid chromatography separation, and bioinformatics-driven data integration, enables the systematic characterization of proteome dynamics to address critical challenges in LC research. These challenges include the discovery of diagnostic and prognostic biomarkers as well as therapeutic targets. By scrutinizing the expression of specific proteins in both normal and cancerous tissues through high-throughput protein microarrays, researchers can uncover novel biomarkers. The use of these biomarkers alone or in combination with established ones holds the potential to significantly advance the fields of LC diagnosis, prognosis, and treatment. In general, the application of proteomics has significantly promoted the development of LC research. In this review, we summarized the latest advancements in the application of proteomics in LC, with a particular focus on diagnosis, prognosis, and treatment. We also concluded selected protein markers, aiming to offer guidance for further applications and present additional therapeutic targets for LC.

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.

This article reviewed the progress in military operational medicine in the U.S.Armed Forces in 2024 in terms of improved capabilities of health care in extreme natural environments,protection from noise damage,sleep interventions,intelligence monitoring of operational efficiency and more academic exchanges in this field.These measures are intended to improve the operational performance of soldiers in every possible way.This article is expected to provide useful references for related research.

Mesenchymal stem cells(MSCs)play a crucial role in tissue repair and regeneration,and the extracellular vesicle(EV)released by them holds great promise for applications in clinical biomarkers,vaccines,and drug delivery.However,MSCs-derived EV(MSCs-EV)face challenges such as low pro-duction yield,poor retention,and targeted delivery issues.There-fore,engineering MSCs-EV to enhance their performance and en-able visual research has become a hot topic.Curcumin(CUR),an active component in traditional chinese medicine,exhibits pharmacological effects but has limited bioavailability.Using MSCs-EV as a carrier for CUR delivery can address its solubility and bioavailability challenges.This article reviews the drug loading methods,engineering strategies of MSCs-EV,and their important applications in the delivery and treatment of CUR for cartilage injury diseases.It provides a basis for the clinical ap-plication of engineered MSCs-EV in CUR delivery for cartilage repair,offering potential solutions to the challenges in cartilage tissue repair.

Objective To establish a performance verification scheme for the metagenomic next-generation sequencing(mNGS)DNA workflow.Methods Reference materials and clinical samples were used for conducting experiments.The mNGS detection results were evaluated in terms of limit of detection(LOD),repeatability,robustness,anti-interference ability,specificity and accuracy,as well as the patterns of library construction and the performance of sequencers.Results All species in the reference materials were stably detected,and the LOD of mNGS was 5.0E+02 CFU/mL(copies/mL).The repeatability was 100％and the within-batch(coefficient of variation)CV ranged from 8.53％to 38.73％.The linear correlation coefficient|r|＞0.9 was found between the input pathogenic microorganism concentration and the read count.Meanwhile,the experimental robustness was found to be good.The results of the anti-interference test showed that the higher concentration of human DNA inputted,the fewer pathogenic microorganism read counts detected by mNGS.Meanwhile,the read counts of related species presented a proportional relationship with the corresponding pathogenic microorganisms concentration inputted,which meant the validation of the cross-interference test had been passed.Furthermore,the detection result of D0 was negative.The accuracy of clinical samples testing was 90.9％(10/11).In addition,the library quality control results obtained by the automatic liquid handling workstation and manually operation were all acceptable.The performance of the three Illumina sequencers met or were better than the factory standards.Conclusion The clinical laboratory performance verification scheme for mNGS detection was established,which included the design for reference materials,comparison of different patterns for library construction,and performance evaluation of the sequencers.More importantly,the performance verification scheme can be used to evaluate and ensure the quality of mNGS DNA workflow detection process.

Objective To validate the diagnostic performance and risk stratification ability of an AI-based recognition system(PE-AI)for pulmonary embolism(PE)using computed tomography pulmonary angiography(CTPA)so as to analyze its diagnostic value in clinical practice.Methods A total of 416 patients with suspected PE who underwent CTPA from January 1,2023 to December 10,2023 at our hospital were included in this study.Two junior radiologists and PE-AI separately detected and diagnosed emboli in the collected cases by double-blind method,and recorded the diagnosis time respectively.Three senior radiologists reviewing with clinical follow-up results were used as the gold standard in this study.Diagnostic performance was evaluated by using the receiver operating characteristic(ROC)curve analysis and Delong-t test.For positive cases,the pulmonary artery obstruction index(PAOI)calculated by AI and manually were collected respectively and consistency analysis was performed.Results The area under the curve(AUC)of PE-AI,manual and combined diagnosis was 85.6％,90.8％and 95.1％,respectively,which differed significantly(P＜0.05).The reading time of PE-AI[(0.16±0.07)min]was significantly lower than the time of manual[(4.42±1.85)min,P＜0.001]and combined diagnosis[(4.58±1.84)min,P＜0.001].The PAOI measured by PE-AI and manually had high consistency(intraclass correlation efficient,ICC=0.80)in the subgroup analysis of confirmed cases.Conclusion AI can quickly identify pulmonary artery emboli in a short time and assist radiologists to improve diagnostic efficiency.At the same time,through the intelligent detection of PAOI,it is helpful for the risk stratification of patients with PE and optimizing the diagnosis and treatment pathway for pulmonary embolism.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.