Objective To explore the role and related mechanism of neutrophil membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice. Methods The male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 μL PBS), NP treatment group (injection of 0.5 mg/mL NP 200 μL), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 μL). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue. Results Neu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-αR and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF-α and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P＜0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P＜0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P＜0.05). Conclusions Neu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Objective:To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose ( 18F-FDG) positron emission computed tomography/computed tomography(PET/CT) in advanced non-small cell lung cancer(NSCLC) treated with first-line immune checkpoint inhibitor (ICI) combined with chemotherapy. Methods:A retrospective study was conducted to evaluate patients with advanced NSCLC who underwent baseline PET/CT before treatment at the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2021. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-offs for metabolic parameters of PET/CT, including total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUV max). Kaplan-Meier method, Log-rank test, and Cox regression model were used to calculate the overall survival (OS) and the progression-free survival(PFS). Results:A total of 44 patients were enrolled. Univariate analysis showed that the factors influencing PFS were TMTV and the number of metastatic sites ( χ2=4.19, 11.28, P<0.05) and the factors influencing OS were TMTV and TLG ( χ2=14.96, 6.05, P<0.05). Multivariate analysis suggested that number of metastatic sites was an independent prognostic marker for PFS ( P=0.011) and TMTV was an independent prognostic marker for OS ( P=0.038). Conclusions:TMTV is a prognostic indicator of OS while the number of metastatic sites is a prognostic indicator of PFS in advanced NSCLC patients who received first-line ICI combined with chemotherapy, but further prospective studies are needed.

Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.

Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

Objective:To investigate the value of artificial intelligence (AI) cytomorphologic analysis system in the cytomorphological diagnosis and therapeutic evaluation of acute myeloid leukemia (AML).Methods:Bone marrow smear samples were collected from 150 patients with newly diagnosed and treated acute myeloid leukemia who were inpatients and outpatients at the Department of Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 1, 2021 to July 31, 2022 for retrospective analysis. Among them, there were 50 patients in the newly diagnosed group, including 28 males and 22 females, with the onset age of 43.5(32.3,58.8)years. There were 100 patients in the post-treatment group, including 36 males and 64 females, with the onset age of 34.5(23.0,47.0)years. The results from cytomorphology expert were used as the gold standard and the Python 3.6.7 was used for analysis to evaluate the accuracy, sensitivity, and specificity of the AI cytomorphologic analysis system for blast cell recognition in AML diagnosis and treatment.Results:The proportion of blasts in AI analysis of 50 samples in the newly diagnosed group was&ge;20%, which met the diagnostic criteria of AML. AI analysis of blasts had an accuracy of 90.3%, sensitivity of 85.5%, and specificity of 98.0%. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.882, P<0.001). Meanwhile, in the post-treatment group, the sensitivity and specificity of AI analysis of blasts were 89.7% and 99.2%, respectively. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.957, P<0.001). According to AI analysis data, there are 8 samples in this group whose AI efficacy evaluation results on AML are inconsistent with expert analysis. Conclusion:AI cytomorphologic analysis system has high accuracy, sensitivity and specificity for blast cell recognition in AML morphological diagnosis and therapeutic evaluation.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.