Exploring the biological basis of CT imaging features in pancreatic neuroendocrine tumors: a two-center study.

Objective.Medical imaging offered a non-invasive window to visualize tumors, with radiomics transforming these images into quantitative data for tumor phenotyping. However, the intricate web linking imaging features, clinical endpoints, and tumor biology was mostly uncharted. This study aimed to unravel the connections between CT imaging features and clinical characteristics, including tumor histopathological grading, clinical stage, and endocrine symptoms, alongside immunohistochemical markers of tumor cell growth, such as the Ki-67 index and nuclear mitosis rate.Approach.We conducted a retrospective analysis of data from 137 patients with pancreatic neuroendocrine tumors who had undergone contrast-enhanced CT scans across two institutions. Our study focused on three clinical factors: pathological grade, clinical stage, and endocrine symptom status, in addition to two immunohistochemical markers: the Ki-67 index and the rate of nuclear mitosis. We computed both predefined (2D and 3D) and learning-based features (via sparse autoencoder, or SAE) from the scans. To unearth the relationships between imaging features, clinical factors, and immunohistochemical markers, we employed the Spearman rank correlation along with the Benjamini-Hochberg method. Furthermore, we developed and validated radiomics signatures to foresee these clinical factors.Main results.The 3D imaging features showed the strongest relationships with clinical factors and immunohistochemical markers. For the association with pathological grade, the mean absolute value of the correlation coefficient (CC) of 2D, SAE, and 3D features was 0.3318 ± 0.1196, 0.2149 ± 0.0361, and 0.4189 ± 0.0882, respectively. While for the association with Ki-67 index and rate of nuclear mitosis, the 3D features also showed higher correlations, with CC as 0.4053 ± 0.0786 and 0.4061 ± 0.0806. In addition, the 3D feature-based signatures showed optimal performance in clinical factor prediction.Significance.We found relationships between imaging features, clinical factors, and immunohistochemical markers. The 3D features showed higher relationships with clinical factors and immunohistochemical markers.

Preoperative Physical Dysfunction Characteristics and Influence Factors Among Elderly Patients with Early Lung Cancer: A Latent Class Analysis.

Objective: To identify latent classes of preoperative physical dysfunction in elderly patients with early lung cancer. To analyze the differences in demographic characteristics between different classes. Methods: We invited elderly patients with early lung cancer who were scheduled for surgery at Shanghai Elderly Characteristic Hospital to participate in the study using a convenience sampling method. We took latent class analysis to divide elderly patients with early lung cancer into latent classes based on preoperative physical dysfunction features. Furthermore, we used single-factor analysis and multinomial logistic regression to investigate the influence variables of each latent class. Results: The characteristics of preoperative physical dysfunction in elderly patients with early lung cancer can be divided into "Anxiety/depression emotion-poor sleep group" "Frailty of physical function group" "Pulmonary hypofunction-low activity tolerance group". The distribution of age, chronic disease history, COPD history, smoking history and perceived social support level of elderly patients with early lung cancer in different potential categories were not the same, and the differences were statistically significant (P<0.05). The elderly lung cancer patients with chronic disease history and age ≥75 years were more likely to be classified as "frailty of physical function group". The elderly lung cancer patients with COPD and smoking history were more likely to be classified into "pulmonary hypofunction-low activity tolerance group". Elderly lung cancer patients with moderate or low degree of perceived social support were more prone to be grouped into "anxiety/depression emotion-poor sleep group". Conclusion: The variety of preoperative physical dysfunction seen in elderly patients with early lung cancer can be categorized into three latent classes. Medical professionals should create strategies for intervention for multiple patient populations with the goal of further enhancing their general state of life.

MicroRNA­373­3p inhibits the proliferation and invasion of non­small­cell lung cancer cells by targeting the GAB2/PI3K/AKT pathway.

MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of non-small-cell lung cancer (NSCLC); however, the roles of certain miRNAs in NSCLC remain to be elucidated. The present study aimed to investigate the functions of screened miRNAs in NSCLC and the potential mechanisms. First, expression profiles of miRNAs were downloaded from the Gene Expression Omnibus (dataset no. GSE29248) and the differentially expressed miRNAs were analyzed by bioinformatics methods. Reverse transcription-quantitative PCR was used to validate the differential expression of miR-373 in clinical samples. The association between miR-373 expression levels and clinicopathological characteristics was also investigated. To further examine how miR-373 mediates the emergence of NSCLC, western blot, Cell Counting Kit-8, cell invasion and wound-healing assays, as well as apoptosis detection and a luciferase assay were used. The results indicated significant downregulation of miR-373 in NSCLC tissues and its low expression was closely associated with the degree of differentiation, clinical stage and tumor size, and was indicative of an unfavorable prognosis for patients with NSCLC. A functional study indicated that overexpression of miR-373 inhibited the proliferation, promoted apoptosis, and suppressed invasion and migration of NSCLC cells. Bioinformatics prediction and functional assays suggested that Grb-associated binding protein 2 (GAB2) was a direct target of miR-373. In addition, GAB2 was found to be significantly upregulated in NSCLC tissues, and clinically, miR-373 was negatively associated with GAB2. Furthermore, overexpression of GAB2 blocked the tumor suppressive effects of miR-373 on NSCLC cells. Mechanistically, miR-373 mimics were able to reduce the expression of GAB2 and subsequently decrease the phosphorylation level of AKT and mTOR protein. The present results indicate that miR-373 exerts its anti-tumor effects in NSCLC cells by targeting the GAB2/PI3K/AKT pathway, suggesting that miR-373 may be a potential therapeutic target in NSCLC.

Deciphering the role of extrachromosomal circular DNA in adipose stem cells from old and young donors.

BACKGROUND: The functional impairment of adipose stem cells (ASCs) during aging limits their clinical transformation. Studies have shown that extrachromosomal circular DNAs (eccDNAs) are associated with tumor progression and cell aging, but the roles of eccDNAs in ASCs remain unknown. METHOD: We conducted Circle sequencing (Circle-seq) to identify eccDNAs in ASCs isolated from young and old donors. The differentially expressed eccDNAs were calculated, annotated and validated via polymerase chain reaction. RESULTS: Thousands of eccDNAs were identified and comprehensively characterized. Most of them were GC-rich, < 1000 base pairs in size, and were enriched on chromosome 19 and 17 with a high density of Alu elements and genes, 2 kb upstream/downstream of genes and satellites. In total, 3025 eccDNAs were differentially expressed among the two ASC groups. Conjoint analysis of the Circle-seq results and previous RNA-seq results revealed that 73 eccDNAs and 55 genes exhibited the same differential expression between the two groups. KEGG and GO analyses revealed that genes encoding differentially expressed eccDNAs were enriched for cell adhesion, cellular senescence and TGF-ß receptor signaling pathway. We also found that aged ASCs exhibited loss of eccDNAs, including CAMK2G (chr10: 75577899-75578176), TRABD2B (chr1: 48305638-48307008) and TRABD2B (chr1: 48305425-48307091). CONCLUSION: In this study, we elucidated the first eccDNA profile relating to ASCs and demonstrated that three eccDNAs are lost in aged ASCs, which may be potential biomarkers of stem cell aging and valuable targets for stem cell rejuvenation.

CT radiomics for noninvasively predicting NQO1 expression levels in hepatocellular carcinoma.

Using noninvasive radiomics to predict pathological biomarkers is an innovative work worthy of exploration. This retrospective cohort study aimed to analyze the correlation between NAD(P)H quinone oxidoreductase 1 (NQO1) expression levels and the prognosis of patients with hepatocellular carcinoma (HCC) and to construct radiomic models to predict the expression levels of NQO1 prior to surgery. Data of patients with HCC from The Cancer Genome Atlas (TCGA) and the corresponding arterial phase-enhanced CT images from The Cancer Imaging Archive were obtained for prognosis analysis, radiomic feature extraction, and model development. In total, 286 patients with HCC from TCGA were included. According to the cut-off value calculated using R, patients were divided into high-expression (n = 143) and low-expression groups (n = 143). Kaplan-Meier survival analysis showed that higher NQO1 expression levels were significantly associated with worse prognosis in patients with HCC (p = 0.017). Further multivariate analysis confirmed that high NQO1 expression was an independent risk factor for poor prognosis (HR = 1.761, 95% CI: 1.136-2.73, p = 0.011). Based on the arterial phase-enhanced CT images, six radiomic features were extracted, and a new bi-regional radiomics model was established, which could noninvasively predict higher NQO1 expression with good performance. The area under the curve (AUC) was 0.9079 (95% CI 0.8127-1.0000). The accuracy, sensitivity, and specificity were 0.86, 0.88, and 0.84, respectively, with a threshold value of 0.404. The data verification of our center showed that this model has good predictive efficiency, with an AUC of 0.8791 (95% CI 0.6979-1.0000). In conclusion, there existed a significant correlation between the CT image features and the expression level of NQO1, which could indirectly reflect the prognosis of patients with HCC. The predictive model based on arterial phase CT imaging features has good stability and diagnostic efficiency and is a potential means of identifying the expression level of NQO1 in HCC tissues before surgery.

Application of multi-modality MRI-based radiomics in the pre-treatment prediction of RPS6K expression in hepatocellular carcinoma.

In this study, we aim to develop and validate a radiomics model for pretreatment prediction of RPS6K expression in hepatocellular carcinoma (HCC) patients, thus helping clinical decision-making of mTOR-inhibitor (mTORi) therapy. We retrospectively enrolled 147 HCC patients, who underwent curative hepatic resection at First Affiliated Hospital Zhejiang University School of Medicine. RPS6K expression was determined with immunohistochemistry staining. Patients were randomly split into training or validation cohorts on a 7:3 ratio. Radiomics features were extracted from T2-weighted and diffusion-weighted images. Machine learning algorithms including multiple logistic regression (MLR), supporting vector machine (SVM), random forest (RF), and artificial neural network (ANN) were applied to construct the predictive model. A nomogram was further built to visualize the possibility of RPS6K expression. The area under the receiver operating characteristic (AUC) was used to evaluate the performance of diagnostic models. 174 radiomics features were confirmed correlated with RPS6K expression. Amongst all built models, the ANN-based hybrid model exhibited best predictive ability with AUC of 0.887 and 0.826 in training and validation cohorts. ALB was identified as the key clinical index, and the nomogram displayed further improved ability with AUC of 0.917 and 0.845. In this study, we proved MRI-based radiomics model and nomogram can accurately predict RPS6K expression non-invasively, thus providing help for clinical decision making for mTORi therapy.

A novel investigation into an E2F transcription factor-related prognostic model with seven signatures for colon cancer patients.

The pathogenesis of colon cancer, a common gastrointestinal tumour, involves complicated factors, especially a series of cell cycle-related genes. E2F transcription factors during the cell cycle play an essential role in the occurrence of colon cancer. It is meaningful to establish an efficient prognostic model of colon cancer targeting cellular E2F-associated genes. This has not been reported previously. The authors first aimed to explore the links of E2F genes with the clinical outcomes of colon cancer patients by integrating data from the TCGA-COAD (n = 521), GSE17536 (n = 177) and GSE39582 (n = 585) cohorts. The Cox regression and Lasso modelling approach to identify a novel colon cancer prognostic model involving several hub genes (CDKN2A, GSPT1, PNN, POLD3, PPP1R8, PTTG1 and RFC1) were utilised. Moreover, an E2F-related nomogram that efficiently predicted the survival rates of colon cancer patients was created. Additionally, the authors first identified two E2F tumour clusters, which showed distinct prognostic features. Interestingly, the potential links of E2F-based classification and 'protein secretion' issues of multiorgans and tumour infiltration of 'T-cell regulatory (Tregs)' and 'CD56dim natural killer cell' were detected. The authors' findings are of potential clinical significance for the prognosis assessment and mechanistic exploration of colon cancer.

The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

Characterization and the cholesterol-lowering effect of dietary fiber from fermented black rice (Oryza sativa L.).

Black rice was fermented with Neurospora crassa, after which the dietary fiber (DF) extracted from it was characterized and evaluated for its cholesterol-lowering effect in mice. The findings demonstrated that fermentation increased the level of soluble DF from 17.27% ± 0.12 to 29.69% ± 0.26 and increased the adsorption capacity of DF for water, oil, cholesterol, glucose and sodium cholate. The fermented DF had a more loose and porous structure than that extracted from unfermented rice. Additionally, feeding with DF from the fermented black rice significantly reduced body weight, lowered total cholesterol levels and improved the lipid profile in mice gavaged with a high dose (5 g per kg bw) or a low dose (2.5 g per kg·bw). ELISA showed that the hepatic expression of typical proteins and enzymes that are involved in cholesterol metabolism was regulated by the fermented rice DF, leading to reduced cholesterol production and increased cholesterol clearance. The fermented DF also modified the gut microbiota composition (e.g. Firmicutes reduced and Akkermansia increased), which promoted the production of short-chain fatty acids. In conclusion, fermentation can modify the structure and function of DF in black rice and the fermented dietary fiber has excellent cholesterol lowering effects possibly by cholesterol adsorption, cholesterol metabolism modulation, and intestinal microflora regulation.

IGF2BP3 aggravates lung adenocarcinoma progression by modulation of PI3K/AKT signaling pathway.

OBJECTIVES: The tumor-promoting function of IGF2BP3 has been reported in several cancers. The present study aimed to explore the function and molecular mechanisms of IGF2BP3 are elusive in lung adenocarcinoma (LUAD). METHODS: IGF2BP3 expression in LUAD and its prognostic value were estimated by bioinformatics. RT-qPCR was employed to detect the expression of IGF2BP3 and confirm the transfection efficiency following the knockdown or overexpression of IGF2BP3. Functional assays, including CCK-8, TUNEL, and Transwell assays, were used to determine the role of IGF2BP3 in tumor cell viability, apoptosis, migration and invasion. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to IGF2BP3 expression. The effects of IGF2BP3 on the PI3K/AKT pathway were detected by western blotting. RESULTS: In this study, we found that IGF2BP3 was overexpressed in LUAD, and patients with high IGF2BP3 levels had a lower probability of overall survival. Moreover, ectopic expression of IGF2BP3 enhanced cell viability and metastasis, and reduced apoptosis. Conversely, IGF2BP3 silencing reduced the viability, migration, and invasion while enhancing the apoptosis of LUAD cells. In addition, it was disclosed that overexpression of IGF2BP3 could activate PI3K/AKT signaling in LAUD, while silencing of IGF2BP3 deactivated this pathway. Moreover, 740Y-P (PI3K agonist) reversed the inhibitory effects on cell viability and metastasis, and the promotion effect on metastasis caused by IGF2BP3 silencing. CONCLUSION: Our findings demonstrated that IGF2BP3 contributed to the tumorigenesis of LUAD by activating the PI3K/AKT signaling.

Stratified treatment of localized cervical esophageal squamous cell carcinoma induced by neoadjuvant immunotherapy plus chemotherapy (SCENIC).

Background: Definitive chemoradiation is the preferred treatment for cervical esophageal carcinoma (CEC), per the National Comprehensive Cancer Network (NCCN) guidelines. However, in treatment failures, salvage surgery poses significant technical challenges. If non-responders could be identified, prior to chemoradiation, these patients may benefit from primary esophagectomy. Programmed cell death protein 1 (PD-1) inhibitor is widely used and recognized as an effective treatment method in various cancers including esophageal cancer. Therefore, we propose to screen for treatment response to neoadjuvant immunotherapy plus chemotherapy to select patients who are radiosensitive and potential candidates for laryngeal preservation. While non-responders are likely to be insensitive to chemoradiation would be offered radical esophagectomy. Methods: A total of 36 patients with histopathologically-confirmed locally advanced CEC have been enrolled in our study. All participants will receive 2 cycles of induction therapy, which was tislelizumab combined with paclitaxel and carboplatin. Patients will be classified into 3 groups according to their response to induction therapy: a remarkable response (RR) group, limited partial response (LPR) group, and poor response (POR) group. Stratified patients will receive the following follow-up treatments: those in the RR group will receive dCRT, and those in the LPR and POR groups will undergo radical surgery. Then, participants in the RR group will be administrated with tislelizumab alone for 1 year. The choice of postoperative treatment for patients in the LPR and POR groups will depend on the patient's condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint of the study is the 2-year event-free survival (EFS). The secondary endpoints are disease-free survival (DFS), regression-free survival (RFS), objective response rate (ORR), and 5-year overall survival (OS). At the same time, we will assess the patient's quality of life (QoL). Conclusions: Screening CEC patients after immune-induction therapy combined with chemotherapy using different treatment strategies might lead to improvements in their QoL and OS time. No relevant double-endpoint studies have been reported until now. Our study is the first multicenter, prospective, exploratory study to seek the optimal treatment for locally advanced CEC patients. The results may offer high-level evidence for future CEC treatment. Trial Registration: Chictr.Org identifier: ChiCTR2200057732.

Small Is Beautiful: Compressing Deep Neural Networks for Partial Domain Adaptation.

Domain adaptation is a promising way to ease the costly data labeling process in the era of deep learning (DL). A practical situation is partial domain adaptation (PDA), where the label space of the target domain is a subset of that in the source domain. Although existing methods yield appealing performance in PDA tasks, it is highly presumable that computation overhead exists in deep PDA models since the target is only a subtask of the original problem. In this work, PDA and model compression are seamlessly integrated into a unified training process. The cross-domain distribution divergence is reduced by minimizing a soft-weighted maximum mean discrepancy (SWMMD), which is differentiable and functions as regularization during network training. We use gradient statistics to compress the overparameterized model to identify and prune redundant channels based on the corresponding scaling factors in batch normalization (BN) layers. The experimental results demonstrate that our method can achieve comparable classification performance to state-of-the-art methods on various PDA tasks, with a significant reduction in model size and computation overhead.

Role of hemoglobin alpha and hemoglobin beta in non-small-cell lung cancer based on bioinformatics analysis.

The differentially expressed genes (DEGs) were identified and screened differentially in non-small-cell lung cancer (NSCLC) using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, and the correlation of DEGs in protein interaction, function, and pathway enrichment were analyzed to search for new biomarkers and potential therapeutic targets for NSCLC. Protein-protein interaction network (PPI) analysis showed that CDK1 and GNGT1 were the most significantly upregulated hub nodes, while FPR2 was the most significantly downregulated. Gene Ontology enrichment analysis showed that upregulated DEGs were significantly enriched in protein heterodimerization activity and other functions, while downregulated DEGs were enriched in functions such as heparin-binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulation of DEGs were significantly associated with neuroactive ligand-receptor interaction pathways, while downregulation of DEGs were significantly associated with malaria pathways. According to the analysis results, we identified hemoglobin alpha (HBA) and hemoglobin beta (HBB) as the genes of interest for further study. Through tissue level and cell level experiments, we found that the expressions of HBA and HBB in NSCLC tissues were significantly lower than those in paracancerous tissues, and downregulation of HBA and HBB could significantly affect the proliferation ability of NSCLC cells. In addition, we also found that changes in HBA and HBB may affect NSCLC cells through the p38/MAPK pathway and JNK pathway, and ultimately affect the occurrence and development of NSCLC.

Follicular Fluid-Derived Exosomal MicroRNA-18b-5p Regulates PTEN-Mediated PI3K/Akt/mTOR Signaling Pathway to Inhibit Polycystic Ovary Syndrome Development.

Small RNA sequences in follicular fluid (FF)-derived exosomes (extracellular vesicles contain proteins, DNA, and RNA) vitally function in the development of polycystic ovary syndrome (PCOS). It has been identified that microRNA (miR)-18b-5p is one of miRs that differ between control and PCOS women that passed the false discovery rate, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important modifier of biological functions of ovarian granulosa cells (GCs) in PCOS. However, whether miR-18b-5p could functionally mediate the progression of PCOS via PTEN was not clarified completely, which was the issue we wanted to solve in our research. FF-derived exosomes were isolated using an extraction kit. KGN cells were co-cultured with miR-18b-5p-modified exosomes or transfected with a PTEN-related vector. After treatment, cell proliferation and apoptosis were observed. A rat model of PCOS was established by letrozole and then injected with miR-18b-5p-modified exosomes. Then, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2) levels in PCOS rats were measured. miR-18b-5p, PTEN, and phosphatidylinositol 3 kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related genes were tested. In PCOS patients, miR-18b-5p was downregulated, and PTEN was highly expressed in FF and GCs. PTEN knockdown increased KGN cell proliferation and limited apoptosis. FF-derived exosomes stimulated proliferation and suppressed apoptosis of KGN cells; decreased FSH, LH, and testosterone; and increased E2 in PCOS rats. Upregulating miR-18b-5p further enhanced the inhibitory effects of exosomes on suppressing the progression of PCOS. miR-18b-5p targeted PTEN and could activate PI3K/Akt/mTOR pathway. miR-18b-5p produced by FF-derived exosomes reduces PTEN expression and promotes the activation of the PI3K/Akt/mTOR signaling pathway to improve PCOS. Based on that, circulating miR-18b-5p levels can contribute to the progression of PCOS complications.

Spatiotemporal Flexible Sparse Reconstruction for Rapid Dynamic Contrast-Enhanced MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a tissue perfusion imaging technique. Some versatile free-breathing DCE-MRI techniques combining compressed sensing (CS) and parallel imaging with golden-angle radial sampling have been developed to improve motion robustness with high spatial and temporal resolution. These methods have demonstrated good diagnostic performance in clinical setting, but the reconstruction quality will degrade at high acceleration rates and overall reconstruction time remains long. In this paper, we proposed a new parallel CS reconstruction model for DCE-MRI that enforces flexible weighted sparse constraint along both spatial and temporal dimensions. Weights were introduced to flexibly adjust the importance of time and space sparsity, and we derived a fast-thresholding algorithm which was proven to be simple and efficient for solving the proposed reconstruction model. Results on both the brain tumor DCE and liver DCE show that, at relatively high acceleration factor of fast sampling, lowest reconstruction error and highest image structural similarity are obtained by the proposed method. Besides, the proposed method achieves faster reconstruction for liver datasets and better physiological measures are also obtained on tumor images.

The short-term outcomes of nonintubated anesthesia compared with intubated anesthesia in single-port video-assisted lung surgery in enhanced recovery after thoracic surgery: results from a single-center retrospective study.

Background: Nonintubated anesthesia avoids invasive tracheal intubation operations and reduces trauma. in addition, it has advantages in lung surgery in some patients with poor lung function, in line with the concept of rapid recovery. However, few studies have discussed the clinical significance of Enhanced recovery after surgery (ERAS) combined with nonintubated anesthesia in single-port video-assisted thoracoscopic surgery (VATS). We conducted a retrospective study to examine the safety and availability of nonintubated anesthesia single-port video-assisted lung surgery (NI-SP-VALS) combined with ERAS programs in patients. Methods: This was a single-center retrospective study. All patients were preoperatively diagnosed with lung nodules and underwent NI-SP-VALS or intubated anesthesia SP-VALS (I-SP-VALS) combined with ERAS programs between July 2021 and March 2022. Short-term postoperative outcomes were compared in 2 cohorts. Results: In total, 272 patients were included. Among them, 91 patients received NI-SP-VALS combined with ERAS programs (observation group), and 181 underwent intubation anesthesia (control group). Baseline data were statistically different between the two groups, and 1:1 propensity score matching (PSM) matching was used. A total of 73 patients remained in each group after PSM, and baseline characteristics were not significantly different between the 2 cohorts. The time of hospital stay [4.00 (4.00-5.00) vs. 44.50 (0.00-5.75) d; P=0.029] and catheter stay [0.50 (0.20-2.00) vs. 2.00 (2.00-2.00) d; P<0.001] were significantly shorter, the white blood cell count (WBC) [9.45 (8.08-11.30) vs. 11 (8.50-12.80)/L; P=0.009] and the lowest SpO2 in operation [96.00 (94.00-97.50) vs. 97.00 (95.00-98.50); P=0.035] were also lower in the nonintubated group than those of the intubated group. No differences were observed in variables of intraoperation, other routine blood indexes, postoperative drainage, postoperative medicine use, postoperative symptoms, complications, hospitalization expenses, postoperative follow-up index, or self-assessment of anxiety. Conclusions: The data after PSM shows that compared with intubated anesthesia, NI-SP-VALS combined with ERAS programs is safe and effective. Nonintubated anesthesia promotes rapid recovery of patients and reduces postoperative inflammatory reactions. Hence, nonintubated anesthesia may conform to the idea of ERAS and has application value in thoracic surgery.

MRI-Radiomics Prediction for Cytokeratin 19-Positive Hepatocellular Carcinoma: A Multicenter Study.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has poor prognosis. Cytokeratin (CK)19-positive (CK19+) HCC is especially aggressive; early identification of this subtype and timely intervention can potentially improve clinical outcomes. In the present study, we developed a preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI)-based radiomics model for noninvasive and accurate classification of CK19+ HCC. A multicenter and time-independent cohort of 257 patients were retrospectively enrolled (training cohort, n = 143; validation cohort A, n = 75; validation cohort B, n = 39). A total of 968 radiomics features were extracted from preoperative multisequence MR images. The maximum relevance minimum redundancy algorithm was applied for feature selection. Multiple logistic regression, support vector machine, random forest, and artificial neural network (ANN) algorithms were used to construct the radiomics model, and the area under the receiver operating characteristic (AUROC) curve was used to evaluate the diagnostic performance of corresponding classifiers. The incidence of CK19+ HCC was significantly higher in male patients. The ANN-derived combined classifier comprising 12 optimal radiomics features showed the best diagnostic performance, with AUROCs of 0.857, 0.726, and 0.790 in the training cohort and validation cohorts A and B, respectively. The combined model based on multisequence MRI radiomics features can be used for preoperative noninvasive and accurate classification of CK19+ HCC, so that personalized management strategies can be developed.

Diagnostic value of miR-153 and miR-203 in patients with cervical cancer and their correlation with human papillomavirus infection.

OBJECTIVE: To explore the diagnostic value of miR-153 and miR-203 in patients with cervical cancer (CC). METHODS: A total of 136 CC and suspected CC patients admitted to our hospital were enrolled in this prospective study. Among them, 80 cases had CC, 56 cases with cervical intraepithelial neoplasia, and 40 cases with cervicitis. The normal cervical tissues of the above 176 patients were taken as a control and the expression levels of miR-153, miR-203 and human papillomavirus (HPV) DNA in CC tissues were detected. RESULTS: The relative expressions of miR-153 and miR-203 in the CC group were significantly lower than those in the cervicitis and cervical intraepithelial neoplasia groups (all P<0.01). The area under the ROC curve of miR-153 for the diagnosis of CC was 0.883 (95% CI: 0.828-0.938, P<0.001). When the cut-off value of miR-153 expression level in the diagnosis of CC was 0.27, its Youden index, specificity, and sensitivity were 0.748, 0.863, and 0.885, respectively. The area under the ROC curve of miR-203 for the diagnosis of CC was 0.752 (95% CI: 0.680-0.825, P<0.001). When the cut-off value of miR-203 expression level in the diagnosis of CC was 0.51, its Youden index, specificity, and sensitivity were 0.478, 0.615, and 0.863, respectively. Compared with the cervical intraepithelial neoplasia group, HPV infection rate in the CC group was significantly higher (P<0.001). The relative expression levels of miR-153 and miR-203 in HPV-positive patients were significantly lower than those in HPV-negative patients (P<0.001). Significantly lower levels of miR-153 and miR-203 were found in patients with myometrial infiltration, FIGO III-IV stage, and lymphatic metastasis (P<0.05). CONCLUSION: The expressions of miR-152 and miR-203 are down-regulated in patients with CC, which has diagnostic value for CC. The expressions of miR-153 and miR-203 are correlated with HPV infection and aggressiveness of tumor.

Persistent Abnormal Immunocytes Induced Systemic Bone Loss in Locally Irradiated Rats.

Chronic and systemic bone complications frequently occur in patients who undergo radiotherapy; however, the pathological mechanisms underlying these complications remain unclear. This study aimed to observe persistent and systemic changes in locally irradiated rats and to determine the systemic pathological changes that persistently affect bone metabolism. We examined the inflammatory and oxidative stress responses that occurred after local irradiation using enzyme immunoassays and biochemical analyses. Lymphocytes obtained from the blood, spleen, thymus, and bone marrow were evaluated using flow cytometry. The proliferation and apoptosis characteristics of co-cultured bone marrow-derived mesenchymal stem cells (BMSCs) were detected by MTT assay and PI/Annexin V-FITC staining, respectively, and the differentiation of BMSCs was measured according to alkaline phosphatase (ALP) staining, alizarin red staining, and Oil Red O staining and by evaluating the mRNA expression of ALP, osteocalcin (OCN), osteopontin (OPN), collagen I, Runx2, and PPARγ. Our results revealed that no significant or continuous differences were present in the inflammatory response or the oxidative stress response throughout the body after local irradiation. B lymphocyte levels increased continuously in the blood, spleen, and bone marrow after local irradiation. T lymphocyte levels were decreased at 2 weeks after local irradiation, and CD8+T lymphocyte levels were increased in the blood, thymus, and bone marrow at 12 weeks after local irradiation. The ratio of CD4+/CD8+T lymphocytes began to decrease during the early phase after local irradiation and became significantly decreased at 12 weeks after local irradiation. Normal BMSCs co-cultured with lymphocytes derived from irradiated rats exhibited decreased proliferation and increased apoptosis, and the ALP staining intensity, alizarin red staining intensity, and mRNA expression of related genes were all also decreased. Oil Red O staining intensity and mRNA expression of PPARγ were both increased. Lymphocyte levels contribute to chronic and systemic bone complications after radiotherapy by inhibiting the proliferation and osteoblastogenesis of BMSCs.