Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To elucidate the effects of miR-616 on the malignant biological processes of osteosarcoma and to preliminarily explore its potential mechanisms.Methods In situ hybridization(ISH)was employed to analyze miR-616 expression in 11 paraffin-embedded osteosarcoma specimens collected in our department during January 2018 to December 2019.Quantitative real-time PCR(qRT-PCR)was used to compare the mRNA expression level of miR-616 in the osteoblast cell line hFOB1.19 and osteosarcoma cell lines 143B and HOS.Stable cell lines with miR-616 knockdown or overexpression were established via lentiviral transfection in 143B and HOS cells.Cell proliferation and apoptosis were detected by flow cytometry,while cell invasion and migration were assessed using Transwell and colony formation assays,respectively.To evaluate the effect of miR-616 on tumor growth in vivo,10 female nude mice(4 weeks old,weighing 18～20 g)were randomized into a control group and a miR-616 overexpression group.After the xenograft tumor model was constructed,the growth of subcutaneous tumors was monitored.Finally,next-generation sequencing and a dual-luciferase reporter assay were performed to identify the target genes of miR-616.Results ISH results showed that miR-616 expression was up-regulated in osteosarcoma tissues than adjacent tissues,and primarily localized in the cytoplasm.qRT-PCR confirmed that miR-616 level was significantly higher in 143B and HOS cells than hFOB1.19 cells(P<0.05).In vitro experiments revealed that miR-616 overexpression enhanced the proliferation,migration and invasion,while suppressing apoptosis in 143B and HOS cells(P<0.01).Conversely,miR-616 knockdown weakened these malignant phenotypes(P<0.05),with miR-616-3p showing a stronger effect on apoptosis than miR-616-5p.Animal experiments demonstrated that the tumor weight in the miR-616 overexpression group was significantly greater than that of the control group(98.00±17.22 vs 33.60±8.08 mg,P<0.01).Furthermore,KLF2 was identified and confirmed as a direct target of miR-616.Conclusion MiR-616 promotes malignant biological behaviors in osteosarcoma,and its expression level indicates that it may serve as a potential therapeutic target.

Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

This paper summarizes Professor YAN Huimin's clinical experience in the staged treatment of pediatric IgA vasculitis. It is believed that the pathogenesis in the acute stage is characterized by fire and heat entering the blood and damaging the collaterals， and the treatment should focus on clearing heat and stopping bleeding， using the self-formulated Qingzi Liangxue Formulation （青紫凉血方）. In the remission stage， the pathogenesis is qi rebellion leading to blood extravasation. The treatment principle is to regulate qi and stabilize blood， using the self-formulated Heqi Ningxue Formulation （和气宁血方）. During the protracted stage， the pathogenesis is latent pathogenic factors due to yin deficiency， and the treatment should aim to nourish the collaterals and strengthen the root， with the self-formulated Yangluo Guben Formulation （养络固本方）. Meanwhile， the method of promoting blood stasis resolution is consistently applied throughout the entire treatment process.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

Objectives:To summarize the experience of echocardiographic diagnosis and the short-term post-operative outcome of children with cardiac tumors. Methods:A total of 27 infants and children,who underwent echocardiography examination and were preliminarily diagnosed with cardiac tumors in Fuwai Hospital from January 2018 to June 2023,were retrospectively included in this study.Clinical symptoms,echocardiographic results,surgical and perioperative results and early outcomes were analyzed. Results:Among the 27 patients,16 were males.The age ranged from 1 month to 11 years(mean age:[3.2±2.5]years)and the body weight ranged from 5.7 to 40.0 kg(mean body weight:[17.2±11.2]kg).Cardiac tumors were pathologically confirmed in 25 cases,including 14 cases of fibroma,5 cases of rhabdomyoma,3 cases of myxoma,2 cases of lipoma,1 case of hemangioma.Preoperative echocardiographic diagnosis was consistent with postoperative pathologic diagnosis in 14 cases.Nontumor lesions were misdiagnosed as tumors by echocardiography in 2 cases.All the patients underwent surgery,complications occurred in 2 cases early post surgery and underwent reoperations and recovered well.There were no deaths during a median follow-up of 29.8(6.5,72.0)months,recurrence occurred in one child with myxoma. Conclusions:Pediatric patients with cardiac tumors have specific echocardiographic manifestations.It is necessary to sum up related experience constantly to improve the diagnostic accuracy.Short-term outcome post-surgery is satisfactory for the treatment of benign pediatric cardiac tumors.

Objective To establish an ideal model of the mitral valve,including the left heart and blood,and study the motion characteristics of the mitral valve in blood flow using the fluid-structure interaction(FSI)simulation.Methods Based on anatomical parameters,models of the mitral valve,left heart,and blood were established.The finite-elements combined immersed boundary method was used for FSI to simulate the motion of the mitral valve using the LS-DYNA software.Morphological,mechanical,and hemodynamic parameters were compared with those obtained from structural simulations.Results The morphological results of the mitral valve from the two simulations differed significantly,and the FSI results matched the ultrasound images.The stress distributions of the leaflets in the FSI and structural simulations were consistent.The maximum first principal stresses calculated by FSI and structural simulations were 1.48 MPa and 1.53 MPa,respectively,with a relative error of 3.27％.The fluid field in the left heart was complex with vortex structures,and the maximum mitral flow velocity was 1.02 m/s during diastole,consistent with the physiological data of healthy humans(0.89±0.15 m/s).Conclusions The morphological results of the mitral valve obtained from the FSI simulation were closer to those in the physiological state.FSI simulations can provide flow patterns that are indispensable for clinical diagnosis.Structural simulations are more efficient for studying leaflet stress distribution.

AIM:This study aimed to investigate the expression and localization of ALOX12P2 in oral squa-mous cell carcinoma(OSCC),as well as its effects on cell viability,migration,and invasion.METHODS:The expres-sion of ALOX12P2 in head and neck squamous cell carcinoma(HNSCC)tissues and its correlation with clinicopathologi-cal features were analyzed using the UALCAN database(University of Alabama at Birmingham Cancer Data Analysis Por-tal).Additionally,the expression of ALOX12P2 in OSCC and its impact on survival prognosis were evaluated through the GDC and UCSC Xena databases.The expression levels of ALOX12P2 in OSCC cell lines were assessed via quantitative re-al-time PCR(RT-qPCR).The subcellular localization of ALOX12P2 was determined using nucleoplasmic RNA isola-tion.CAL-27 cells were used to establish an ALOX12P2 knockdown group(SS-ALOX12P2)and a control group(SS-NC).HN30 cells were employed to form an ALOX12P2 overexpression group(ALOX12P2)and a control group(vector).The effects of altered ALOX12P2 expression on the epithelial-mesenchymal transition(EMT)-related gene E-cadherin and the PI3K/AKT signaling pathway were assessed through Western blot analysis.RESULTS:ALOX12P2 expression was significantly higher in HNSCC and OSCC tissues compared to normal tissues,with its expression correlating with poor prog-nosis.RT-qPCR analysis indicated that the relative expression of ALOX12P2 in OSCC cells was comparable to that in nor-mal cells(P<0.05).RNA nucleoplasmic isolation confirmed that ALOX12P2 localized in the nucleus.In comparison to the SS-NC group,the SS-ALOX12P2 group exhibited a marked reduction in ALOX12P2 expression(P<0.01),alongside significant decreases in cell viability,migration,and invasion(P<0.01).Conversely,the ALOX12P2 group showed sub-stantially higher relative expression compared to the vector group(P<0.01),with enhanced cell viability,migration,and invasion abilities(P<0.01).Western blot analysis demonstrated that ALOX12P2 knockdown resulted in upregulation of E-cadherin and downregulation of N-cadherin and Vimentin(P<0.01),while overexpression of ALOX12P2 yielded the opposite effects(P<0.01).Knockdown of ALOX12P2 led to decreased protein expression of p-PI3K and p-AKT(P<0.01),whereas overexpression increased these protein levels(P<0.01).CONCLUSION:ALOX12P2 is highly ex-pressed in OSCC and promotes cell viability,migration,and invasion.This effect may be linked to the activation of the PI3K/AKT signaling pathway,which facilitates the epithelial-mesenchymal transition(EMT)process.

Objective To construct a comorbidity network for medical expenses by analyzing the rele-vant medical records,and to construct a deep learning prediction model by combining with the disease net-works and long short-term memory neural networks in order to improve the accuracy of individual medical ex-pense prediction and provide the assistance for optimizing the medical policies and enhancing the patient health management level.Methods Based on the medical records of Taiwan,China Health Insurance Research Data-base during 2000-2013,the data of 5.84 million visits from 9 963 patients were analyzed,and a comorbidity network of medical expenses for 104 common diseases was constructed.The network structure was analyzed and the potential comorbidity was predicted,and the deep learning model of individual medical cost was con-structed by combining the input of patient's gender,age,medical history and other information.Results The constructed medical cost comorbidity network consists of 104 nodes,3 390 edges and 6 modules,and is a high-ly connected network with nodes,indicating that the medical costs possesses the high correlation between dis-eases.The constructed deep learning prediction model significantly improves the prediction accuracy compared to the traditional regression models and deep learning models that do not fully consider the comorbidity infor-mation.Conclusion The constructed model provides a new theoretical perspective for understanding the co-morbidity of diseases,as well as an effective tool for accurately predicting medical costs,optimizing medical re-source allocation and achieving the personalized medical services.

Objective:To investigate the relationship between the cardia morphology under magnetically controlled capsule gastroscopy and the clinical characteristics of subjects.Methods:A total of 216 subjects with gastrointestinal symptoms or receiving physical examination who underwent magnetically controlled capsule gastroscopy at the Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University from August 2022 to November 2022 were enrolled. All subjects took gastroesophageal reflux disease questionnaire (Gerd-Q) survey. Clinical data of subjects were collected, and images of cardia morphology under magnetically controlled capsule gastroscopy were recorded. The subjects were divided into 4 groups according to differrent cardia morphology based on the degree of relaxation. The clinical characteristics of each group were compared, and the influencing factors for cardia morphology were analyzed.Results:In non-swallowing state, 116 subjects showed good continuous closure of the cardia in plum shape (group A), 33 subjects radial closure of cardia (group B), 46 subjects slightly relaxed linear cardia (group C) and 21 subjects relaxed and continuous opening of cardia in the shape of cave (group D). The ages of subjects in group A, B, C and D were 35.00 (31.00, 42.00) years, 53.00 (37.50, 60.50) years, 61.50 (41.50, 68.25) years and 52.00 (39.00, 70.00) years, respectively, with significant differences ( H=44.348, P<0.001). The Gerd-Q scores of subjects in group A, B, C and D were 1.50 (1.00, 2.00), 3.00 (2.00, 6.50), 8.00 (5.75, 9.00) and 8.00 (7.50, 9.00), respectively, with significant differences ( H=90.788, P<0.001). The body mass index (BMI) of subjects in group A, B, C and D were 22.66 (19.53, 24.70) kg/m 2, 23.44 (21.41, 27.05) kg/m 2, 23.77 (21.19, 26.93) kg/m 2 and 23.73 (19.63,24.79) kg/m 2, respectively, with significant differences ( H=8.114, P=0.044). The degree of cardia relaxation was positively correlated with the age ( rs=0.456, P<0.001), Gerd-Q score ( rs=0.648, P<0.001) and BMI ( rs=0.146, P=0.032) of subjects. Conclusion:The magnetically controlled capsule gastroscopy provides good visualisation of cardia morphology in non-swallowing state. There is a positive correlation between the degree of cardia relaxation under magnetically controlled capsule gastroscopy in non-swallowing state and the subjects' age, Gerd-Q score, and BMI.