Establishment of a neutrophil extracellular trap-related prognostic signature for colorectal cancer liver metastasis and expression validation of CYP4F3.

Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM.

Programmable activation of berbamine and photosensitizers for enhanced photodynamic therapy using emission-switchable upconversion nanoparticles.

Photodynamic therapy (PDT) shows great potential in precision tumor treatment. However, its efficacy is inhibited by the antioxidant defense capacities of tumor cells. To address this challenge, a near-infrared light-controlled nanosystem (UCNPs@mSiO2@Azo@ZnPc&BBM, PB@UA) was developed using emission-switchable upconversion nanoparticles (UCNPs) to independently and precisely control the release of berbamine (BBM) and activation of photosensitizer for enhanced PDT in deep tissues. Firstly, BBM release was triggered by exciting PB@UA at 980 nm. The BBM could inhibit the activities of antioxidant enzymes and disrupt calcium ion regulation, making the tumor cells more susceptible to ROS-induced cell death in the following PDT treatment. The PDT was initiated by irradiating the photosensitizers of ZnPc on PB@UA at 808 nm and achieved a tumor inhibition rate of 80.91 % in vivo, which is significantly higher than that of unique PDT (31.78 %) or BBM (11.29 %) treatment and demonstrates the potential of our strategy for improved cancer treatment.

Effects of integrated nursing and psychological intervention on pain relief and patient satisfaction in urinary calculi patients.

OBJECTIVE: We aimed to assess the impact of integrated nursing and psychological intervention on pain intensity and patient satisfaction in individuals with urinary calculi. METHODS: This retrospective study included 94 urological patients from the Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, between January 2020 and June 2022. Participants were divided into a control group (n=48), receiving routine nursing and psychological intervention, and a study group (n=46), receiving integrated nursing and psychological intervention. We compared pain intensity, pain relief rate, patient satisfaction, Numeric Rating Scale (NRS) score, Pittsburgh Sleep Quality Index (PSQI) score, Self-rating Depression Scale (SDS) score, Self-rating Anxiety Scale (SAS) score, and quality of life scores between the groups. RESULTS: The study group had shorter hospital stays and lower hospitalization costs than the control group (both P < 0.05). Pain relief and satisfaction rates were higher in the study group (both P < 0.05). Post-intervention, both groups showed significant reductions in NRS, PSQI, SDS, and SAS scores, with greater reductions in the study group (all P < 0.05). Quality of life scores increased in both groups, more so in the SG (P < 0.05). The study group also had fewer adverse events (P < 0.05). Both groups showed decreased serum creatinine and blood urea nitrogen levels post-intervention, with a more significant decline in the study group (P < 0.05). Education, marital status, and occupation were major factors influencing outcomes in urinary calculi patients. CONCLUSION: Integrated nursing and psychological intervention significantly alleviates pain, improves emotional well-being, enhances sleep quality, increases overall life quality, and contributes to high patient satisfaction among urinary calculi patients.

Weighted gene co-expression network analysis reveals key biomarkers and immune infiltration characteristics for bronchial epithelial cells from asthmatic patients.

BACKGROUND: Asthma ranks among the most prevalent non-communicable diseases worldwide. Previous studies have elucidated the significant role of the immune system in its pathophysiology. Nevertheless, the immune-related mechanisms underlying asthma are complex and still inadequately understood. Thus, our objective was to investigate novel key biomarkers and immune infiltration characteristics associated with asthma by employing integrated bioinformatics tools. METHODS: In this study, we conducted a weighted gene co-expression network analysis (WGCNA) to identify key modules and genes potentially implicated in asthma. Functional annotation of these key modules and genes was carried out through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, we constructed a protein-protein interaction (PPI) network using the STRING database to identify 10 hub genes. Furthermore, we evaluated the relative proportion of immune cells in bronchial epithelial cell samples from 20 healthy individuals and 88 asthmatic patients using CIBERSORT. Finally, we validated the hub genes and explored their correlation with immune infiltration. RESULTS: Furthermore, 20 gene expression modules and 10 hub genes were identified herein. Among them, complement component 3 (C3), prostaglandin I2 receptor (PTGIR), parathyroid hormone-like hormone (PTHLH), and C-X3-C motif chemokine ligand 1 (CX3CL1) were closely correlated with the infiltration of immune cells. They may be novel candidate biomarkers or therapeutic targets for asthma. Furthermore, B cells memory, and plasma cells might play an important role in immune cell infiltration after asthma. CONCLUSIONS: C3, PTGIR, CX3CL1, and PTHLH have important clinical diagnostic values and are correlated with infiltration of multiple immune cell types in asthma. These hub genes, B cells memory, and plasma cells may become important biological targets for therapeutic asthma drug screening and drug design.

A ROS storm generating nanocomposite for enhanced chemodynamic therapy through H2O2 self-supply, GSH depletion and calcium overload.

Catalytic generation of toxic hydroxyl radicals (˙OH) from hydrogen peroxide (H2O2) is an effective strategy for tumor treatment in chemodynamic therapy (CDT). However, the intrinsic features of the microenvironment in solid tumors, characterized by limited H2O2 and overexpressed glutathione (GSH), severely impede the accumulation of intracellular ˙OH, posing significant challenges. To circumvent these critical issues, in this work, a CaO2-based multifunctional nanocomposite with a surface coating of Cu2+ and L-buthionine sulfoximine (BSO) (named CaO2@Cu-BSO) is designed for enhanced CDT. Taking advantage of the weakly acidic environment of the tumor, the nanocomposite gradually disintegrates, and the exposed CaO2 nanoparticles subsequently decompose to produce H2O2, alleviating the insufficient supply of endogenous H2O2 in the tumor microenvironment (TME). Furthermore, Cu2+ detached from the surface of CaO2 is reduced by H2O2 and GSH to Cu+ and ROS. Then, Cu+ catalyzes H2O2 to generate highly cytotoxic ˙OH and Cu2+, forming a cyclic catalysis effect for effective CDT. Meanwhile, GSH is depleted by Cu2+ ions to eliminate possible ˙OH scavenging. In addition, the decomposition of CaO2 by TME releases a large amount of free Ca2+, resulting in the accumulation and overload of Ca2+ and mitochondrial damage in tumor cells, further improving CDT efficacy and accelerating tumor apoptosis. Besides, BSO, a molecular inhibitor, decreases GSH production by blocking γ-glutamyl cysteine synthetase. Together, this strategy allows for enhanced CDT efficiency via a ROS storm generation strategy in tumor therapy. The experimental results confirm and demonstrate the satisfactory tumor inhibition effect both in vitro and in vivo.

Integrated analysis of scRNA-seq and bulk RNA-seq identifies FBXO2 as a candidate biomarker associated with chemoresistance in HGSOC.

Background: High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and aggressive histological subtype of epithelial ovarian cancer. Around 80% of individuals will experience a recurrence within five years because of resistance to chemotherapy, despite initially responding well to platinum-based treatment. Biomarkers associated with chemoresistance are desperately needed in clinical practice. Methods: We jointly analyzed the transcriptomic profiles of single-cell and bulk datasets of HGSOC to identify cell types associated with chemoresistance. Copy number variation (CNV) inference was performed to identify malignant cells. We subsequently analyzed the expression of candidate biomarkers and their relationship with patients' prognosis. The enrichment analysis and potential biological function of candidate biomarkers were explored. Then, we validated the candidate biomarker using in vitro experiments. Results: We identified 8871 malignant epithelial cells in a single-cell RNA sequencing dataset, of which 861 cells were associated with chemoresistance. Among these malignant epithelial cells, FBXO2 (F-box protein 2) is highly expressed in cells related to chemoresistance. Moreover, FBXO2 expression was found to be higher in epithelial cells from chemoresistance samples compared to those from chemosensitivity samples in a separate single-cell RNA sequencing dataset. Patients exhibiting elevated levels of FBXO2 experienced poorer outcomes in terms of both overall survival (OS) and progression-free survival (PFS). FBXO2 could impact chemoresistance by influencing the PI3K-Akt signaling pathway, focal adhesion, and ECM-receptor interactions and regulating tumorigenesis. The 50% maximum inhibitory concentration (IC50) of cisplatin decreased in A2780 and SKOV3 ovarian carcinoma cell lines with silenced FBXO2 during an in vitro experiment. Conclusions: We determined that FBXO2 is a potential biomarker linked to chemoresistance in HGSOC by combining single-cell RNA-seq and bulk RNA-seq dataset. Our results suggest that FBXO2 could serve as a valuable prognostic marker and potential target for drug development in HGSOC.

Single-cell RNA sequencing reveals distinct transcriptomic profiles and evolutionary patterns in lung cancer brain metastasis.

Background: Lung cancer metastasis to the brain presents significant clinical challenges. Therefore, elucidating its underlying mechanisms and characterizing its transcriptomic landscape is essential for developing therapeutic interventions. Methods: We analyzed two distinct single-cell RNA sequencing datasets of lung cancer metastasis to analyze the evolutionary trajectory of brain metastatic tumors. In addition, a systematic comparison of cell-cell interaction between tumor cells and lymphocytes was conducted within primary and brain metastatic tumors. Results: The brain metastatic tumors showed greater transcriptomic changes (reflected by a higher pseudotime) than tumors in the lymph nodes and primary tumors. Furthermore, our investigation has not only revealed specific shared ligand-receptor pairs in both mLN and mBrain, exemplified by the interaction between SPP1 and CD99 in T cells, but has also unveiled a diverse array of ligand-receptor pairs exclusive to the mBrain. Notably, this includes distinctive pairs such as APP and IL1 observed specifically in myeloid cells. Conclusion: The distinct microenvironment in the brain may influence the observed transcriptomic changes in tumors, emphasizing the significance of the specific environment in determining tumor behavior and therapeutic response.

Unveiling the best predictive models for early­onset metastatic cancer: Insights and innovations (Review).

Cancer metastasis is the primary cause of cancer deaths. Metastasis involves the spread of cancer cells from the primary tumors to other body parts, commonly through lymphatic and vascular pathways. Key aspects include the high mutation rate and the capability of metastatic cells to form invasive tumors even without a large initial tumor mass. Particular emphasis is given to early metastasis, occurring in initial cancer stages and often leading to misdiagnosis, which adversely affects survival and prognosis. The present review highlighted the need for improved understanding and detection methods for early metastasis, which has not been effectively identified clinically. The present review demonstrated the clinicopathological and molecular characteristics of early­onset metastatic types of cancer, noting factors such as age, race, tumor size and location as well as the histological and pathological grade as significant predictors. In conclusion, the present review underscored the importance of early detection and management of metastatic types of cancer and called for improved predictive models, including advanced techniques such as nomograms and machine learning, so as to enhance patient outcomes, acknowledging the challenges and limitations of the current research as well as the necessity for further studies.

The role of vasoactive intestinal peptide (VIP) in atropine-related inhibition of the progression of myopia.

OBJECTIVE: This study aimed to investigate the potential involvement of vasoactive intestinal polypeptide (VIP) in myopia development and its contribution to the mechanism of action of the anti-myopia drug, atropine. METHODS: Thirty-three-week-old guinea pigs were randomly divided into normal control (NC, n = 10), monocularly form-deprived (FDM, n = 10), and FDM treated with 1% atropine (FDM + AT, n = 10) groups. The diopter and axial length were measured at 0, 2, and 4 weeks. Guinea pig eyeballs were removed at week four, fixed, and stained for morphological changes. Immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to evaluate VIP protein and mRNA levels. RESULTS: The FDM group showed an apparent myopic shift compared to the control group. The results of the H&E staining were as follows: the cells of the inner/outer nuclear layers and retinal ganglion cells were disorganized; the choroidal thickness (ChT), blood vessel lumen, and area were decreased; the sclera was thinner, with disordered fibers and increased interfibrillar space. IHC and ISH revealed that VIP's mRNA and protein expressions were significantly up-regulated in the retina of the FDM group. Atropine treatment attenuated FDM-induced myopic shift and fundus changes, considerably reducing VIP's mRNA and protein expressions. CONCLUSIONS: The findings of elevated VIP mRNA and protein levels observed in the FDM group indicate the potential involvement of VIP in the pathogenesis and progression of myopia. The ability of atropine to reduce this phenomenon suggests that this may be one of the molecular mechanisms for atropine to control myopia.

TRIM65 knockout inhibits the development of HCC by polarization tumor-associated macrophages towards M1 phenotype via JAK1/STAT1 signaling pathway.

BACKGROUND & AIMS: Tumor-associated macrophages (TAMs) are main components of immune cells in tumor microenvironment (TME), and play a crucial role in tumor progression. Tripartite motif-containing protein 65 (TRIM65) has been associated with tumor progression. However, whether TRIM65 regulate the interaction of tumor cell and TAMs in HCC and the underlying mechanisms remain unknown. In this study, we investigated the role of TRIM65 in TME of HCC and explored its underlying mechanisms. METHODS: The relation of TRIM65 expression level with tumor grades, TNM stages, and worse prognosis of HCC patients was evaluated by bioinformatics analysis, as well as immune infiltration level of macrophages. TRIM65 shRNA was transfected into HepG2 cells, and TRIM65 overexpression plasmid was transfected into Huh7 cells, and the effect of TRIM65 on cell growth was examined by EdU assay. The mouse subcutaneous Hep1-6 tumor-bearing model with WT and TRIM65-/- mice was established to study the role of TRIM65 in HCC. Immunohistochemistry staining, Immunofluorescence staining, qRT-PCR and western blot were performed to evaluate the effect of TRIM65 on TAM infiltration, TAM polarization and JAK1/STAT1 signaling pathway. RESULTS: Bioinformatics analysis revealed that TRIM65 was upregulated in 16 types of cancer especially in HCC, and high level of TRIM65 was strongly correlated with higher tumor grades, TNM stages, and worse prognosis of patients with HCC as well as immune infiltration level of macrophages (M0, M1, and M2). Moreover, we observed that TRIM65 shRNA-mediated TRIM65 knockdown significantly inhibited the HepG2 cells growth while TRIM65 overexpression highly increased the Huh7 cells growth in vitro. TRIM65 knockout significantly inhibited the tumor growth as well as macrophages polarization towards M2 but promoted macrophages polarization towards M1 in vivo. Mechanistically, the results demonstrate that TRIM65 knockout promoted macrophage M1 polarization in conditioned medium-stimulated peritoneal macrophages and in tumor tissues by activating JAK1/STAT1 signaling pathway. CONCLUSIONS: Taken together, our study suggests that tumor cells utilize TRIM65-JAK1/STAT1 axis to inhibit macrophage M1 polarization and promote tumor growth, reveals the role of TRIM65 in TAM-targeting tumor immunotherapy.

A Multilabel Text Classifier of Cancer Literature at the Publication Level: Methods Study of Medical Text Classification.

BACKGROUND: Given the threat posed by cancer to human health, there is a rapid growth in the volume of data in the cancer field and interdisciplinary and collaborative research is becoming increasingly important for fine-grained classification. The low-resolution classifier of reported studies at the journal level fails to satisfy advanced searching demands, and a single label does not adequately characterize the literature originated from interdisciplinary research results. There is thus a need to establish a multilabel classifier with higher resolution to support literature retrieval for cancer research and reduce the burden of screening papers for clinical relevance. OBJECTIVE: The primary objective of this research was to address the low-resolution issue of cancer literature classification due to the ambiguity of the existing journal-level classifier in order to support gaining high-relevance evidence for clinical consideration and all-sided results for literature retrieval. METHODS: We trained a multilabel classifier with scalability for classifying the literature on cancer research directly at the publication level to assign proper content-derived labels based on the "Bidirectional Encoder Representation from Transformers (BERT) + X" model and obtain the best option for X. First, a corpus of 70,599 cancer publications retrieved from the Dimensions database was divided into a training and a testing set in a ratio of 7:3. Second, using the classification terminology of International Cancer Research Partnership cancer types, we compared the performance of classifiers developed using BERT and 5 classical deep learning models, such as the text recurrent neural network (TextRNN) and FastText, followed by metrics analysis. RESULTS: After comparing various combined deep learning models, we obtained a classifier based on the optimal combination "BERT + TextRNN," with a precision of 93.09%, a recall of 87.75%, and an F1-score of 90.34%. Moreover, we quantified the distinctive characteristics in the text structure and multilabel distribution in order to generalize the model to other fields with similar characteristics. CONCLUSIONS: The "BERT + TextRNN" model was trained for high-resolution classification of cancer literature at the publication level to support accurate retrieval and academic statistics. The model automatically assigns 1 or more labels to each cancer paper, as required. Quantitative comparison verified that the "BERT + TextRNN" model is the best fit for multilabel classification of cancer literature compared to other models. More data from diverse fields will be collected to testify the scalability and extensibility of the proposed model in the future.

Comparison of setup accuracy of optical surface image versus orthogonal x-ray images for VMAT of the left breast using deep-inspiration breath-hold.

To compare the setup accuracy of optical surface image (OSI) versus orthogonal x-ray images (2DkV) using cone beam computed tomography (CBCT) as ground truth for radiotherapy of left breast cancer in deep-inspiration breath-hold (DIBH). Ten left breast DIBH patients treated with volumetric modulated arc therapy (VMAT) were studied retrospectively. OSI, 2DkV, and CBCT were acquired weekly at treatment setup. OSI, 2DkV, and CBCT were registered to planning CT or planning DRR based on a breast surface region of interest (ROI), bony anatomy (chestwall and sternum), and both bony anatomy and breast surface, respectively. These registrations provided couch shifts for each imaging system. The setup errors, or the difference in couch shifts between OSI and CBCT were compared to those between 2DkV and CBCT. A second OSI was acquired during last beam delivery to evaluate intrafraction motion. The median absolute setup errors were (0.21, 0.27, 0.23 cm, 0.6°, 1.3°, 1.0°) for OSI, and (0.26, 0.24, 0.18 cm, 0.9°, 1.0°, 0.6°) for 2DkV in vertical, longitudinal and lateral translations, and in rotation, roll and pitch, respectively. None of the setup errors was significantly different between OSI and 2DkV. For both systems, the systematic and random setup errors were ≤0.6 cm and ≤1.5° in all directions. Nevertheless, larger setup errors were observed in some sessions in both systems. There was no correlation between OSI and CBCT whereas there was modest correlation between 2DkV and CBCT. The intrafraction motion in DIBH detected by OSI was small with median absolute translations <0.2 cm, and rotations ≤0.4°. Though OSI showed comparable and small setup errors as 2DkV, it showed no correlation with CBCT. We concluded that to achieve accurate setup for both bony anatomy and breast surface, daily 2DkV can't be omitted following OSI for left breast patients treated with DIBH VMAT.

Reproducibility of chestwall and heart position using surface-guided versus RPM-guided DIBH radiotherapy for left breast cancer.

This study compared the reproducibility of chestwall and heart position using surface-guided versus RPM (real-time position management)-guided deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer. Forty DIBH patients under either surface-guided radiotherapy (SGRT) or RPM guidance were studied. For patients treated with tangential fields, reproducibility was measured as the displacements in central lung distance (CLD) and heart shadow to field edge distance (HFD) between pretreatment MV (megavoltage) images and planning DRRs (digitally reconstructed radiographs). For patients treated with volumetric modulated arc therapy (VMAT), sternum to isocenter (ISO) distance (StID), spine to rib edge distance (SpRD), and heart shadow to central axis (CAX) distance (HCD) between pretreatment kV images and planning DRRs were measured. These displacements were compared between SGRT and RPM-guided DIBH. In tangential patients, the mean absolute displacements of SGRT versus RPM guidance were 0.19 versus 0.23 cm in CLD, and 0.33 versus 0.62 cm in HFD. With respect to planning DRR, heart appeared closer to the field edge by 0.04 cm with surface imaging versus 0.62 cm with RPM. In VMAT patients, the displacements of surface imaging versus RPM guidance were 0.21 versus 0.15 cm in StID, 0.24 versus 0.19 cm in SpRD, and 0.72 versus 0.41 cm in HCD. Heart appeared 0.41 cm further away from CAX with surface imaging, whereas 0.10 cm closer to field CAX with RPM. None of the differences between surface imaging and RPM guidance was statistically significant. In conclusion, the displacements of chestwall were small and were comparable with SGRT- or RPM-guided DIBH. The position deviations of heart were larger than those of chestwall with SGRT or RPM. Although none of the differences between SGRT and RPM guidance were statistically significant, there was a trend that the position deviations of heart were smaller and more favorable with SGRT than with RPM guidance in tangential patients.

Dissecting cellular heterogeneity and intercellular communication in cholangiocarcinoma: implications for individualized therapeutic strategies.

Background: Cholangiocarcinoma is characterized by significant cellular heterogeneity and complex intercellular communication, which contribute to its progression and therapeutic resistance. Therefore, unraveling this complexity is essential for the development of effective treatments. Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and intercellular communication in cholangiocarcinoma and adjacent normal tissues from two patients. Distinct cell types were identified, and gene ontology analyses were conducted to determine enriched pathways. Moreover, cell-cell communications were analyzed using CellChat, a computational framework. Additionally, we performed sub-clustering analysis of T cells and fibroblasts. Results: The scRNA-seq analysis revealed distinct cell clusters and diverse cellular compositions of cholangiocarcinoma. CellChat analysis underscored an amplified outgoing signal from fibroblasts within the tumor, suggesting their pivotal role in the tumor microenvironment. Furthermore, T cell sub-clustering analysis revealed an active immune response within the tumor and new tumor-specific T cell clonotypes, suggesting scope for targeted immunotherapies. Moreover, fibroblast sub-clustering analysis indicated distinct functional states and highlighted the role of activated fibroblasts in shaping intercellular communication, particularly via CD99 and FN1 signaling. Conclusion: Our findings reveal the intricate cellular heterogeneity and dynamic intercellular communication in cholangiocarcinoma, providing valuable insights into disease progression and potential therapeutic strategies.

The effectiveness of web-based interventions on non-alcoholic fatty liver disease (NAFLD) in obese children: A study protocol for a randomized controlled trial.

Aim: Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease in the world, increasing the risk of cirrhosis and hepatocellular carcinoma, and contributing to the development of type 2 diabetes, cardiovascular disease, and chronic kidney disease. This study aims to carry out a web-based continuum of a care intervention model to provide comprehensive care interventions for obese children with NAFLD, to improve the effectiveness of treatment of children with NAFLD. Design: A 1-year single-blinded randomized clinical trial in hospital in Zhejiang Province. Methods: Eighty subjects will implement the program in a randomized order. The interventions for the control group mainly consisted of the routine distribution of health education materials and health education by holding health-themed lectures, and the preliminary proposed interventions including establishing management teams, regularly delivering related health knowledge, daily uploading of health intervention records, regular supervision and mutual encouragement, home visiting and psychological guidance. The primary outcomes are serum biomarkers such as alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), aspartate aminotransferase, and imaging (liver ultrasound and magnetic resonance imaging). Second outcomes are: BMI, waist-to-hip ratio and quality of life. In addition, socio-demographic characteristics such as age, gender and ethnicity will be recorded. Children aged 7-18 years old and diagnosed with NAFLD will be included, patients will be not eligible if they do not agree to participate or are participating in other health intervention programs. This study was registered on ClinicalTrials.gov (NCT05527938). Results: Over the past 30 years, NAFLD has been recognized as one of the most common liver diseases in adults and children. The current studies have focused on promoting lifestyle changes in children with NASH by providing some education and advice to children and their families to improve the histological features of NASH and lose weight. Because of the convenience and efficiency of the internet can provide some new strategies and ways for lifestyle interventions for children with NAFLD. In addition, we have designed a high-quality RCT based on the SPIRIT guidelines, which also provides strong evidence in this area.

Clinical characteristics and gene mutation profiles of chronic obstructive pulmonary disease in non-small cell lung cancer.

Purpose: The coexistence of chronic obstructive pulmonary disease (COPD) often leads to a worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, approaches targeting specific genetic alterations have been shown to significantly improve the diagnosis and treatment outcomes of patients with NSCLC. Herein, we sought to evaluate the impact of COPD on the clinical manifestations and gene mutation profiles of NSCLC patients with both circulating tumor (ctDNA) and tumor DNA (tDNA). Materials and methods: The influence of COPD on clinical features was observed in 285 NSCLC cohorts suffering from NSCLC alone, NSCLC coexisting with COPD, or NSCLC coexisting with prodromal changes in COPD (with emphysema, bullae, or chronic bronchitis). The gene mutation profiles of specific 168 NSCLC-related genes were further analyzed in the NSCLC sub-cohorts with formalin-fixed and paraffin-embedded tumor DNA (FFPE tDNA) samples and plasma circulating tumor DNA (PLA ctDNA) samples. Moreover, mutation concordance was assessed in tDNA and paired ctDNA of 110 NSCLC patients. Results: Relative to patients with NSCLC alone, patients with NSCLC coexisting with COPD and prodromal changes presented with worse lung functions, more clinical symptoms, signs and comorbidities, and inconsistent gene mutation profiles. In addition, patients in the latter two groups exhibited a higher average frequency of gene mutation. Lastly, mutation concordance between tDNA and ctDNA samples was significantly reduced in NSCLC patients coexisting with COPD. Conclusions: Collectively, our findings revealed that coexistence of COPD leads to worse clinical manifestations and altered gene mutation profiles in patients with NSCLC. Additionally, for NSCLC patients with COPD, the use of ctDNA instead of tDNA may not be the most efficient approach to identifying gene mutations.

Cataract surgery is not associated with post-operative binocular vision anomalies in age-related cataract patients.

PURPOSE: To compare the binocular vision status of patients pre- and post-cataract surgery, and to investigate the risk factors for patients who develop binocular vision anomalies post-surgery. METHODS: A prospective study of patients (≥50 years) who elected to undergo bilateral cataract surgery was implemented. A comprehensive binocular vision test battery including stereopsis, ocular alignment, fusional vergence, vergence facility, near point of convergence and the Convergence Insufficiency Symptom Survey (CISS) was administered before the first surgery and at the third visit after surgery on the second eye. A detailed diagnostic classification protocol was applied to identify the presence of binocular vision anomalies pre- and post-surgery. RESULTS: Seventy-three participants were included at baseline, 24 (33%) of whom were diagnosed with non-strabismic binocular vision anomalies (NSBVA), mainly convergence insufficiency (18/73, 25%). Fifty-one participants completed the post-operative evaluation, 17 (33%) of whom had NSBVA pre-surgery and 13 (26%) post-surgery (p = 0.48). There were a number of conversions from NSBVA to normal binocular vision and vice versa. Logistic regression showed that the adjusted odds ratio of pre-existing NSBVA diagnosis for predicting the risk of post-operative NSBVA was 6.37 (p < 0.01). There were no significant changes in most binocular vision measures post-surgery, except for a significant improvement in the CISS score (p < 0.01, Cohen's d = 0.83). CONCLUSIONS: Binocular vision anomalies, especially convergence insufficiency, are prevalent in the age-related cataract population. Cataract surgery does not appear to be a significant risk factor for the development of new binocular vision anomalies. A pre-existing binocular vision anomaly is the main risk factor for predicting a post-operative binocular vision anomaly in this population.

Preoperative binocular vision characteristics in the age-related cataract population.

BACKGROUND: This study is the first part of the "Binocular Vision Anomalies after Cataract Surgery" study that aimed to investigate the impact of cataract surgery on binocular vision status in adults with age-related cataract. This study aimed to investigate the preoperative binocular vision status of participants with age-related cataract. METHODS: Patients who elected to undergo bilateral cataract surgery (≥50 years of age) were recruited. Clinical measures of binocular vision including stereopsis, ocular alignment, fusional vergence, vergence facility, convergence amplitude and a symptom survey related to binocular vision anomalies were administered. A detailed classification protocol was established to identify the presence of binocular vision anomalies. The frequency of specific binocular vision anomalies and normative data of binocular vision measures were reported. RESULTS: A total of 73 subjects were evaluated. No strabismus was detected in the cohort. Non-strabismic binocular vision anomalies were detected in 24 subjects (32.9%), of whom 18 (24.7%) had convergence insufficiency, 3 (4.1%) had basic exophoria, 2 (2.7%) had convergence excess, and 1 (1.4%) had fusional vergence dysfunction. Decreased vergence facility and convergence amplitude were more common compared to the pre-presbyopes (P < 0.01). CONCLUSION: Binocular vision problems, especially convergence insufficiency, are common in the adults with age-related cataract. The study results demonstrate that the lack of normative binocular vision data for the presbyopic population is a significant gap in the literature and suggest the need for a study of normative data for this population. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT03592615, USA).

AAPM task group report 302: Surface-guided radiotherapy.

The clinical use of surface imaging has increased dramatically, with demonstrated utility for initial patient positioning, real-time motion monitoring, and beam gating in a variety of anatomical sites. The Therapy Physics Subcommittee and the Imaging for Treatment Verification Working Group of the American Association of Physicists in Medicine commissioned Task Group 302 to review the current clinical uses of surface imaging and emerging clinical applications. The specific charge of this task group was to provide technical guidelines for clinical indications of use for general positioning, breast deep-inspiration breath hold treatment, and frameless stereotactic radiosurgery. Additionally, the task group was charged with providing commissioning and on-going quality assurance (QA) requirements for surface-guided radiation therapy (SGRT) as part of a comprehensive QA program including risk assessment. Workflow considerations for other anatomic sites and for computed tomography simulation, including motion management, are also discussed. Finally, developing clinical applications, such as stereotactic body radiotherapy (SBRT) or proton radiotherapy, are presented. The recommendations made in this report, which are summarized at the end of the report, are applicable to all video-based SGRT systems available at the time of writing.