Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

Characterization of a novel anti-PVRIG antibody with Fc-competent function that exerts strong antitumor effects via NK activation in preclinical models.

Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade.

The roles of gut microbiome and metabolites associated with skin photoaging in mice by intestinal flora sequencing and metabolomics.

Photoaging of skin, a chronic disease, can produce the appearance changes and cancer lesions of skin. Therefore, it is of great significance to investigate the mechanisms and explore effective methods to treat the disorder. Gut microbiota and intestinal metabolisms have critical roles in a variety of diseases. However, their roles on photoaging of skin were not well tested. In the present work, the results showed that compared with control group, the levels of MDA, SOD and CAT associated with oxidative stress, the levels of COL I, CER, and HA associated with skin function, and the mRNA levels of IL-1ß, IL-6, TNF-α associated with inflammation after long-term exposure to ultraviolet radiation in mice were significantly changed. Skin pathological tissue was also seriously damaged. The protein levels of AQP3 and FLG were significantly decreased. Ultraviolet exposure also promoted skin photoaging by activating TNFR1/TRAF2-mediated MAPK pathway, in which the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2 were significantly increased in model mice compared with control group. In fecal microbiota transplantation (FMT) experiment, we found that the intestinal microbiome of control mice alleviated skin photoaging via adjusting the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2. 16S rRNA sequencing found that 1639 intestinal bacteria were found, in which 15 bacteria including norank_f_Ruminococcaceae, Lachnospirac -eae_NK4A136_group, Lachnoclostridium, etc., were significantly different at the genus level. Untargeted GC-TOF/MS and UHPLC-MS/MS metabolomics showed 72 and 188 metabolites including taurine, ornithine, L-arginine, L-histidine, sucrose with significant differences compared with control group. Then, amino acid targeting assay showed 10 amino acids including L-ornithine, L-arginine and L-citrulline with higher levels in control group compared with model group. In addition, we also found that the variation of Lachnoclostridium abundance may regulate L-arginine metabolism to affect skin photoaging. Some intestinal bacteria and metabolites including amino acids may be closely related to skin photoaging, which should provide new methods to treat skin photoaging in the future.

Efficient gene delivery by multifunctional star poly (ß-amino ester)s into difficult-to-transfect macrophages for M1 polarization.

Gene delivery to macrophages holds great promise for cancer immunotherapy. However, traditional gene delivery methods exhibit low transfection efficiency in macrophages. The star-shaped topological structure of polymers is known to encapsulate genes inside their cores, thereby facilitating sustained release of the genetic material. Herein, combining the structural advantages of star polymers and the transfection advantages of poly (ß-amino ester)s (PAEs), we developed a novel linear oligomer grafting-onto strategy to synthesize a library of multi-terminal star structured PAEs (SPAEs), and evaluated their gene delivery efficiency in various tissue cells. The transfection with human hepatocellular carcinoma cells (HepG2, HCC-LM3 cells and MHCC-97H cells), rat normal liver cells (BRL-3 A cells), human ovarian cancer cells (A2780 cells), African green monkey kidney cells (Vero cells), human cervical cancer cells (HeLa cells), human chondrosarcoma cells (SW1353 cells), and difficult-to-transfect human epidermal keratinocytes (HaCaT cells) and normal human fibroblast cells (NHF cells) showed that SPAEs exhibited superior transfection profile. The GFP transfection efficiency of top-performing SPAEs in HeLa cells (96.1%) was 2.1-fold, and 3.2-fold higher compared to jetPEI and Lipo3000, respectively, indicating that the star-shaped topological structure can significantly enhance the transfection efficiency of PAEs. More importantly, the top-performing SPAEs could efficiently deliver Nod2 DNA to difficult-to-transfect RAW264.7 macrophages, with a high transfection efficiency of 33.9%, which could promote macrophage M1 polarization and enhanced CD8+ T cell response in co-incubation experiments. This work advances gene therapy by targeting difficult-to-transfect macrophages and remodeling the tumor immune microenvironment.

Correlation Between B-Cell Activating Factor of the Tumor Necrosis Factor Family Level in Serum and Immune Inflammation in Patients with Neuropsychiatric Systemic Lupus Erythematosus and its Clinical Value.

OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a form of SLE associated with severe NP syndromes causing mortality and morbidity. Respecting the fundamental of BAFF in NPSLE pathophysiology, we investigated its clinical value. METHODS: Totally 105 NPSLE and 101 SLE cases without NPSLE (non-NPSLE, control) were included. Serum BAFF/TNF-α/IL-6/IL-10 levels were measured using ELISA kits. T lymphocytes were detected by flow cytometry. The independent influencing factors for NPSLE, and the auxiliary diagnostic efficacy and the ability of BAFF levels to predict adverse prognosis of NPSLE patients were analyzed by multiple factor logistic regression, and ROC curve and survival curve. RESULTS: In NPSLE patients, serum BAFF level was increased and positively correlated with SLEDAI-2k, serum proinflammatory cytokines, while negatively correlated with CD4+T/CD8+T cells, and anti-inflammatory cytokine. High serum BAFF protein level was associated with a higher risk of developing NPSLE. The AUC of serum BAFF > 301.7 assisting in NPSLE diagnosis was 0.8196. Furthermore, high levels of serum BAFF were associated with a higher risk of adverse outcomes in NPSLE patients. . CONCLUSION: Serum BAFF level in NPSLE patients was correlated with lymphocytes and high serum BAFF protein level could assist in diagnosis and to predict adverse outcomes in NPSLE patients.

O-GlcNAcylation mediates H2O2-induced apoptosis through regulation of STAT3 and FOXO1.

The O-linked-ß-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is a critical post-translational modification that couples the external stimuli to intracellular signal transduction networks. However, the critical protein targets of O-GlcNAcylation in oxidative stress-induced apoptosis remain to be elucidated. Here, we show that treatment with H2O2 inhibited O-GlcNAcylation, impaired cell viability, increased the cleaved caspase 3 and accelerated apoptosis of neuroblastoma N2a cells. The O-GlcNAc transferase (OGT) inhibitor OSMI-1 or the O-GlcNAcase (OGA) inhibitor Thiamet-G enhanced or inhibited H2O2-induced apoptosis, respectively. The total and phosphorylated protein levels, as well as the promoter activities of signal transducer and activator of transcription factor 3 (STAT3) and Forkhead box protein O 1 (FOXO1) were suppressed by OSMI-1. In contrast, overexpressing OGT or treating with Thiamet-G increased the total protein levels of STAT3 and FOXO1. Overexpression of STAT3 or FOXO1 abolished OSMI-1-induced apoptosis. Whereas the anti-apoptotic effect of OGT and Thiamet-G in H2O2-treated cells was abolished by either downregulating the expression or activity of endogenous STAT3 or FOXO1. These results suggest that STAT3 or FOXO1 are the potential targets of O-GlcNAcylation involved in the H2O2-induced apoptosis of N2a cells.

Can Hisense computer-assisted surgery system (Hisense CAS) improve anatomy teaching in pediatric liver surgery?

PURPOSE: This study aimed to investigate the effectiveness of the Hisense computer-assisted surgery system (CAS) in teaching pediatric liver surgical anatomy. METHODS: The research subjects were residents who underwent standardized training at the Department of Pediatric Surgery at Yijishan Hospital of Wannan Medical College from May 2022 to May 2023. RESULTS: The study recruited a total of 62 students, with 31 students assigned to the Hisense CAS group (12 males and 19 females) and the remaining 31 students serving as controls (Control group, 15 males and 16 females). There were no significant differences in baseline characteristics observed between the two groups. This study found that the average scores of the Hisense CAS teaching group in the liver surgery evaluations were higher than those of the control group. Specifically, the Hisense CAS group had an average score of 84.25 ± 5.70 points in the liver surgery knowledge test, 77.10 ± 8.12 points in the image reading test, and 70.58 ± 8.79 points in the surgical simulation test, while the traditional teaching group had average scores of 73.45 ± 6.12 points, 69.81 ± 6.05 points, and 66.42 ± 6.61 points, respectively; the differences between the two groups were statistically significant (P < 0.05). Furthermore, this study also found that the Hisense CAS teaching model resulted in significantly better teaching satisfaction on the part of the residents in terms of standardized teaching for physicians in pediatric liver surgical anatomy. CONCLUSION: In conclusion, this study demonstrated greater satisfaction of the residents with the use of 3D reconstruction added to traditional teaching sessions and better performance during the posttraining evaluation.

Intratumor injected gold molecular clusters for NIR-II imaging and cancer therapy.

Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3-Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation.

Identification of angiogenesis-related subtypes, the development of a prognosis model, and features of tumor microenvironment in colon cancer.

Angiogenesis is associated with tumor progression, prognosis, and treatment effect. However, the angiogenesis' underlying mechanisms in the tumor microenvironment (TME) still remain unclear. Understanding the dynamic interactions between angiogenesis and TME in colon adenocarcinoma (COAD) is necessary. We downloaded the transcriptome data and corresponding clinical data of colon cancer patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct angiogenesis-related molecular subtypes (subtype A and subtype B) and assessed the clinical features, prognosis, and infiltrating immune cells of patients in the two subtypes. According to the prognostic differential genes, we defined two different gene clusters to further explore the correlation between angiogenesis and tumor heterogeneity. Then, we construct the prognostic risk scoring model angiogenesis-related gene (ARG-score) including seven genes (ARMCX2, latent transforming growth factor ß binding protein 1, ADAM8, FABP4, CCL11, CXCL11, ITLN1) using Lasso-multivariate cox method. We analyzed the correlation between ARG-score and prognosis, clinicopathological features, TME, molecular feature, cancer stem cells (CSCs), and microsatellite instability (MSI) status. To assess the application value of ARG-score in clinical treatment, immunophenotype score was used to predict patients' immunotherapy response in colon cancer. We found the mutations of ARGs in TCGA-COAD dataset from genetic levels and discussed their expression patterns based on TCGA and GEO datasets. We observed important differences in clinicopathological features, prognosis, immune feature, molecular feature between the two molecular subgroups. Then, we established an ARG-score for predicting OS and validated its predictive capability. A high ARG-score characterized by higher transcription level of ARGs, suggested lower MSI-high (MSI-H), lower immune score, and worse clinical stage and survival outcome. Additionally, the ARG-score was remarkably related to the CSCs index and immunotherapy sensitivity. We found two new molecular subtypes and two gene clusters based on ARGs and established an ARG-score. Multilayered analysis revealed that ARGs were remarkably correlated to the heterogeneity of colon cancer patients and explained the process of tumorigenesis and progression better. The ARG-score can help us better assess patients' survival outcomes and provide guidance for individualized treatment.

Solitary Pulmonary Fibroleiomyomatous Hamartoma on 18 F-FDG PET/CT.

ABSTRACT: Solitary pulmonary fibroleiomyomatous hamartoma is a very rare benign tumor. A 57-year-old man presented with dry cough over 1 month. A CT showed an irregular nodule in the left upper lobe of the lung. A malignant tumor was suspected, and further investigation with 18 F-FDG PET/CT showed the pulmonary nodule with slightly increased FDG uptake. Thoracoscopic resection was performed. Subsequent histopathological and immunohistochemical tests confirmed the diagnosis of fibroleiomyomatous hamartoma.

Feasibility study of cryoballoon ablation for atrial fibrillation with KODEX-EPD: a single center experience.

To evaluate the feasibility of cryoballoon (CB) ablation of atrial fibrillation (AF) under the guidance of a new three-dimensional (3D) mapping system KODEX-EPD. 40 patients scheduled for CB ablation of AF in the first affiliated Hospital of Xinjiang Medical University from August 2021 to July 2022 were randomly divided into two groups: KODEX-EPD 3D mapping system guidance group (KODEX group, n = 20) and conventional two-dimensional perspective group (standard group, n = 20). The ablation time, operation time, fluoroscopy time, fluoroscopy dose, contrast agent dosage and follow-up data were compared between the two groups. Besides, the feasibility and accuracy of the dielectric sensing system in evaluating pulmonary vein (PV) occlusion in patients with AF during CB ablation were verified. All pulmonary veins were being isolated. The ablation time (36.40 ± 6.72 min vs 35.15 ± 6.29 min, P > 0.05) and the operation time (64.20 ± 11.82 min vs 66.00 ± 13.18 min, P > 0.05) were not statistically different in the two groups. The standard group has longer fluoroscopy time, dose and contrast medium dosage. There were significant differences in fluoroscopy time (532.30 ± 72.83 s vs 676.25 ± 269.33 s, P < 0.05), fluoroscopy dose (110.00 ± 28.64 mGy vs 144.68 ± 66.66 mGy, P < 0.05), and contrast medium dosage (71.90 ± 5.97 ml vs 76.05 ± 5.93 ml, P < 0.05) between the two groups. The learning curves of the first 5 patients and the last 15 patients in the KODEX group were compared. There was no statistical difference in the ablation time (36.80 ± 8.56 min vs 36.27 ± 6.34 min, P > 0.05) or the operation time (69.00 ± 5.00 min vs 62.60 ± 13.10 min, P > 0.05); however, compared to the first 5 patients, fluoroscopy time (587.40 ± 38.34 s vs 513.93 ± 73.02 s, P < 0.05), fluoroscopy dose (147.85 ± 35.19 mGy vs 97.39 ± 8.80 mGy, P < 0.05) and contrast medium dosage (79.60 ± 1.14 ml vs 69.33 ± 4.45 ml, P < 0.05) were significantly decreased. Using pulmonary venography as the gold standard, the sensitivity, specificity of the completely occlusion in KODEX group was 93.6% (95% CI 85-97.6%) and 69.6% (95% CI 54-81.8%); and the sensitivity, specificity of the small leak in KODEX group was 93.1% (95% CI 82.4-97.8%) and 82.0% (95% CI 65.9-91.9%). During an average follow-up of (9.90 ± 1.06) months, there was no statistical difference in arrhythmia recurrence and antiarrhythmic drugs taking after CB ablation between the two groups (P > 0.05). Using the KODEX-EPD system, the CB ablation procedure can correctly evaluate the PV occlusion, and significantly reduce fluoroscopy exposure and contrast medium without significantly increasing the operation time.

NOP58 induction potentiates chemoresistance of colorectal cancer cells through aerobic glycolysis as evidenced by proteomics analysis.

Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood. Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein. Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116-5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU. Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance.

Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). However, 20-40% of patients with LARC show little to no response to nCRT. Thus, comprehensively understanding the tumor microenvironment (TME), which might influence therapeutic efficacy, and identifying robust predictive biomarkers is urgently needed. Pre-treatment tumor biopsy specimens from patients with LARC were evaluated in detail through digital spatial profiling (DSP), public RNA sequencing datasets, and multiplex immunofluorescence (mIF). DSP analysis revealed distinct characteristics of the tumor stroma compared to the normal stroma and tumor compartments. We identified high levels of human leukocyte antigen-DR/major histocompatibility complex class II (HLA-DR/MHC-II) in the tumor compartment and B cells in the stroma as potential spatial predictors of nCRT efficacy in the Discovery cohort. Public datasets validated their predictive capacity for clinical outcomes. Using mIF in an independent nCRT cohort and/or the total cohort, we validated that a high density of HLA-DR/MHC-II+ cells in the tumor and CD20 + B cells in the stroma was associated with nCRT efficacy (all p ≤ 0.021). Spatial profiling successfully characterized the LARC TME and identified robust biomarkers with the potential to accurately predict nCRT response. These findings have important implications for individualized therapy.

Therapeutic effects of low-color-temperature light-emitting diodes on dry eye.

BACKGROUND: As a new technology for treating dry eye diseases, phototherapy has attracted great attention, but the research on its safety and effectiveness is limited. In this study, the therapeutic effects of low-color-temperature light-emitting diodes on dry eye in humans, rabbits, and rats were investigated. METHODS: In clinical experiments, subjects in both groups read the same paper for 3 h under light sources of two color temperatures: 1900 K (low-color-temperature light-emitting diodes) or 4000 K (artificial fluorescent white light-emitting diodes). The differences in the non-invasive tear film breakup time, tear meniscus height, and conjunctival congestion scores before and after the experiment were compared between the two groups. In animal experiments, corneal epithelial barrier function and tear production of Sprague-Dawley rats and New Zealand white rabbits with dry eye were compared before and after low-color-temperature light-emitting diodes treatment. TUNEL staining and Western blotting were used to detect the apoptosis of corneal and conjunctival cells and the expression of inflammatory factor IL-1ß. RESULTS: Low-color-temperature light-emitting diodes prolonged tear film breakup time in patients with dry eye. Moreover, it increased tear secretion, decreased fluorescein sodium staining scores, corneal and conjunctival cell apoptosis, and inflammatory factor expression in rabbits and rats with dry eye. CONCLUSIONS: Low-color-temperature light-emitting diodes phototherapy can be used as an effective treatment for dry eye, reducing its symptoms and related ocular surface damage in humans, rabbits, and rats.

Nonpharmacological Interventions for Management of the Pain-Fatigue-Sleep Disturbance Symptom Cluster in Breast Cancer Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: The pain-fatigue-sleep disturbance symptom cluster is commonly experienced by breast cancer patients, and a variety of nonpharmacological interventions are used to treat this symptom cluster. Objective: To compare the efficacy of nonpharmacological interventions in improving the symptoms of the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, CNKI, and Wanfang databases to identify randomized controlled studies from database inception to May 2022. Two reviewers independently performed data retrieval and risk of bias assessments. The consistency model was used to conduct network meta-analyses (NMA) based on the frequentist framework to assess the interventions, which were ranked by the surface under the cumulative ranking curve (SUCRA). Finally, the CINeMA application was used to evaluate the results of the NMA and the evidence of quality. The results Twenty-three eligible studies assessing 14 interventions were included. According to SUCRA values, among the management effects of the three symptoms, the effect of progressive muscle relaxation (PMR) ranked first, followed by mindfulness-based stress reduction (MBSR). The overall evidence quality of our study ranges from very low to moderate. Conclusion: PMR and MBSR were effective interventions for the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Clinical recommendations prioritize PMR for symptom management, followed by MBSR. However, this should be interpreted cautiously, as the confidence in the evidence was not high.

Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses.

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF4/NaYF4 core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8+ T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8+-T-cell-targeted NaYbF4/NaYF4 nanoparticles and H-2Kb/ovalbumin257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies.

IL-2Rα-biased agonist enhances antitumor immunity by invigorating tumor-infiltrating CD25+CD8+ T cells.

To avoid regulatory T cell promotion and vascular toxicity, the interleukin-2 receptor-ß/interleukin-2 receptor-γ (IL-2Rßγ)-biased approach is used by most IL-2 analogs in immuno-oncology. However, recent clinical disappointments in these IL-2 agonists have questioned this strategy. Here we show that both wild-type (IL-2wt) and IL-2Rßγ-attenuated (IL-2α-bias) agonists that preserve IL-2Rα (CD25) activities can effectively expand tumor-specific CD8+ T cells (TSTs) and exhibit better antitumor efficacy and safety than the 'non-α' counterpart (IL-2nα). Mechanistically, TSTs coexpress elevated CD25 and PD-1 and are more susceptible to stimulation by IL-2Rα-proficient agonists. Moreover, the antitumor efficacy of anti-PD-1 depends on activation of PD-1+CD25+ TSTs through autocrine IL-2-CD25 signaling. In individuals with cancer, a low IL-2 signature correlates with non-responsiveness to anti-PD-1 treatment. In mouse models, IL-2α-bias, but not IL-2nα, restores the IL-2 signature and synergizes with anti-PD-1 to eradicate large established tumors. These findings underscore the indispensable function of CD25 in IL-2-based immunotherapy and provide rationales for evaluating IL-2Rα-biased agonists in individuals with cancer.

Magnetic resonance imaging analysis of embryonal rhabdomyosarcoma of the prostate.

BACKGROUND: Rhabdomyosarcoma (RMS) is a highly malignant tumor that originates from myogenic progenitor cells. OBJECTIVE: To investigate the magnetic resonance imaging (MRI) characteristics of prostate embryonal rhabdomyosarcoma (ERMS). METHODS: We retrospectively analyzed the clinical and MRI imaging data of 9 cases of prostate ERMS that were confirmed pathologically. The patients were aged between 14∼49 years with a median age of 27 years, and they all underwent MRI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI). RESULTS: The MRI scan of the lesions showed an irregular shape, mixed signals, uneven equal/long T1 signal and an equal/long T2 signal, cystic necrosis in 9 cases and hemorrhage in 6 cases; DWI and ADC images showed a mixed high/low signal, and the tumor parenchyma showed ADC low signal, with an average ADC value of 0.666 × 10-3 mm2/s. There were 5 cases of DCE-MRI TIC type II and 4 cases of DCE-MRI TIC type I. The average value of Tpeak was 120 s and the average value of MCER was 172.3%. After the enhancement, the signal of tumor enhancement was uneven, and showed patchy and reticular enhancement, however, the cyst degeneration, necrosis area, and hemorrhage focus were not enhanced. There were 3 cases with multiple pelvic lymph nodes and 1 case with multiple bone metastases. CONCLUSION: The MRI manifestations of prostate ERMS have certain characteristics, and the combination of DWI and DCE-MRI are helpful in the diagnosis.

Prior information-assisted integrative analysis of multiple datasets.

MOTIVATION: Analyzing genetic data to identify markers and construct predictive models is of great interest in biomedical research. However, limited by cost and sample availability, genetic studies often suffer from the "small sample size, high dimensionality" problem. To tackle this problem, an integrative analysis that collectively analyzes multiple datasets with compatible designs is often conducted. For regularizing estimation and selecting relevant variables, penalization and other regularization techniques are routinely adopted. "Blindly" searching over a vast number of variables may not be efficient. RESULTS: We propose incorporating prior information to assist integrative analysis of multiple genetic datasets. To obtain accurate prior information, we adopt a convolutional neural network with an active learning strategy to label textual information from previous studies. Then the extracted prior information is incorporated using a group LASSO-based technique. We conducted a series of simulation studies that demonstrated the satisfactory performance of the proposed method. Finally, data on skin cutaneous melanoma are analyzed to establish practical utility. AVAILABILITY AND IMPLEMENTATION: Code is available at https://github.com/ldz7/PAIA. The data that support the findings in this article are openly available in TCGA (The Cancer Genome Atlas) at https://portal.gdc.cancer.gov/.