RNA modifications in pulmonary diseases.

Threatening public health, pulmonary disease (PD) encompasses diverse lung injuries like chronic obstructive PD, pulmonary fibrosis, asthma, pulmonary infections due to pathogen invasion, and fatal lung cancer. The crucial involvement of RNA epigenetic modifications in PD pathogenesis is underscored by robust evidence. These modifications not only shape cell fates but also finely modulate the expression of genes linked to disease progression, suggesting their utility as biomarkers and targets for therapeutic strategies. The critical RNA modifications implicated in PDs are summarized in this review, including N6-methylation of adenosine, N1-methylation of adenosine, 5-methylcytosine, pseudouridine (5-ribosyl uracil), 7-methylguanosine, and adenosine to inosine editing, along with relevant regulatory mechanisms. By shedding light on the pathology of PDs, these summaries could spur the identification of new biomarkers and therapeutic strategies, ultimately paving the way for early PD diagnosis and treatment innovation.

A radiomics strategy based on CT intra-tumoral and peritumoral regions for preoperative prediction of neoadjuvant chemoradiotherapy for esophageal cancer.

OBJECTIVE: Develop a method for selecting esophageal cancer patients achieving pathological complete response with pre-neoadjuvant therapy chest-enhanced CT scans. METHODS: Two hundred and one patients from center 1 were enrolled, split into training and testing sets (7:3 ratio), with an external validation set of 30 patients from center 2. Radiomics features from intra-tumoral and peritumoral images were extracted and dimensionally reduced using Student's t-test and least absolute shrinkage and selection operator. Four machine learning classifiers were employed to build models, with the best-performing models selected based on accuracy and stability. ROC curves were utilized to determine the top prediction model, and its generalizability was evaluated on the external validation set. RESULTS: Among 16 models, the integrated-XGBoost and integrated-random forest models performed the best, with average ROC AUCs of 0.906 and 0.918, respectively, and RSDs of 6.26 and 6.89 in the training set. In the testing set, AUCs were 0.845 and 0.871, showing no significant difference in ROC curves. External validation set AUCs for integrated-XGBoost and integrated-random forest models were 0.650 and 0.749. CONCLUSION: Incorporating peritumoral radiomics features into the analysis enhances predictive performance for esophageal cancer patients undergoing neoadjuvant chemoradiotherapy, paving the way for improved treatment outcomes.

A retrospective study on the effect of Chinese patent medicine combined with conventional treatment on the survival outcomes of 313 patients with stage II-III NSCLC.

PURPOSE: We aim to explore the effect of Chinese Patent Medicine (CPM), including Huisheng oral solution (HSOS) on the 4-year survival rate of patients with stage II and III non-small cell lung cancer, and assess the association between blood coagulation indicators and survival outcomes. MATERIALS AND METHODS: 313 patients diagnosed with stage II and III NSCLC were collected during 2015-2016. Kaplan-Meier method and Cox proportional hazard model were applied to analyze the factors affecting the 4-year survival rate of patients. RESULTS: According to the effect of CPM, the medicine prescribed in this study could be classified into two types. The proportion of patients who received "Fuzheng Quyu" CPM for more than three months was higher than the proportion of patients who received other two types of CPM for more than three months. Medical records of 313 patients with NSCLC were analyzed. 4-year survival rate for patients received CPM more than 6 months and 3 months were higher than those received CPM less than 3 months (P = 0.028 and P = 0.021 respectively. In addition, 4-year survival rate for patients who received HSOS for more than 3 months was higher than those who received HSOS for less than 3 months (P = 0.041). Patients with elevated preoperative fibrinogen (FIB) level and those without surgery had an increased mortality risk (HR = 1.98, P < 0.01, and HR = 2.76, P < 0.01 respectively). CONCLUSION: The medium and long-term use of CPM/HSOS was positively associated with higher survival rate in NSCLC patients. Patients with high-level preoperative FIB level and those without surgery might have a poor prognosis in the following years.

Prediction model of death risk in patients with sepsis and screening of biomarkers for prognosis of patients with myocardial injury.

This study aimed to create a robust prediction model for sepsis patient mortality and identify key biomarkers in those with myocardial injury. A retrospective analysis of 261 sepsis inpatients was conducted, with 44 deaths and 217 recoveries. Key factors were assessed via univariate and multivariate analyses, revealing myocardial injury, shock, and pulmonary infection as independent mortality risk factors. Using LASSO regression, a reliable prediction model was developed and internally validated. Additionally, procalcitonin (PCT) emerged as a sensitive biomarker for myocardial injury prediction in sepsis patients. In summary, this study highlights myocardial injury, shock, and pulmonary infection as independent risk factors for sepsis-related deaths. The LASSO-based prediction model effectively forecasts the prognosis of septic patients with myocardial injury, with PCT showing promise as a predictive biomarker.

Type III interferon exerts thymic stromal lymphopoietin in mediating adaptive antiviral immune response.

Previously, it was believed that type III interferon (IFN-III) has functions similar to those of type I interferon (IFN-I). However, recently, emerging findings have increasingly indicated the non-redundant role of IFN-III in innate antiviral immune responses. Still, the regulatory activity of IFN-III in adaptive immune response has not been clearly reported yet due to the low expression of IFN-III receptors on most immune cells. In the present study, we reviewed the adjuvant, antiviral, antitumor, and disease-moderating activities of IFN-III in adaptive immunity; moreover, we further elucidated the mechanisms of IFN-III in mediating the adaptive antiviral immune response in a thymic stromal lymphopoietin (TSLP)-dependent manner, a pleiotropic cytokine involved in mucosal adaptive immunity. Research has shown that IFN-III can enhance the antiviral immunogenic response in mouse species by activating germinal center B (GC B) cell responses after stimulating TSLP production by microfold (M) cells, while in human species, TSLP exerts OX40L for regulating GC B cell immune responses, which may also depend on IFN-III. In conclusion, our review highlights the unique role of the IFN-III/TSLP axis in mediating host adaptive immunity, which is mechanically different from IFN-I. Therefore, the IFN-III/TSLP axis may provide novel insights for clinical immunotherapy.

The predictive value of a computed tomography-based radiomics model for the surgical separability of thymic epithelial tumors from the superior vena cava and the left innominate vein.

Background: The aim of this study was to develop a radiomics machine learning model based on computed tomography (CT) that can predict whether thymic epithelial tumors (TETs) can be separated from veins during surgery and to compare the accuracy of the radiomics model to that of radiologists. Methods: Patients who underwent thymectomy at our hospital from 2009 to 2017 were included in the screening process. After the selection of patients according to the inclusion and exclusion criteria, the cohort was randomly divided into training and testing groups, and CT images of these patients were collected. Subsequently, two-dimensional (2D) and three-dimensional (3D) regions of interest were labelled using ITK-SNAP 3.8.0 software, and Radiomics features were extracted using Python software (Python Software Foundation) and selected through the least absolute shrinkage and selection operator (LASSO) regression model. To construct the classifier, a support vector machine (SVM) was employed, and a nomogram was created using logistic regression to predict vascular inseparable TETs based on the radiomics score (radscore) and image features. To assess the accuracy of these models, area under receiver operating characteristic (ROC) curves of these models were calculated, and differences among the models were identified using the Delong test. Results: In this retrospective study, 204 patients with TETs were included, among whom 21 were diagnosed with surgical vascularly inseparable TETs. The area under ROC curve (AUC) of the 2D model, 3D model, 2D + 3D model, and radiologist diagnoses were 0.94, 0.92, 0.95, and 0.87 in the training cohort and 0.95, 0.92, 0.98, and 0.78 in testing cohort, respectively. The Delong test revealed a significant improvement in the performance of the radiomics models compared to radiologists' diagnoses. The logistic regression selected 3 image features, namely maximum diameter of the tumor, degree of abutment of vessel circumference >50%, and absence of the mediastinal fat layer or space between the tumor and surrounding structures. These features, along with the radscore, were included to develop a nomogram. The AUCs of this nomogram were 0.99 in both the training set and testing set, and the Delong test did not find a significant difference between ROC plots of the nomogram and radiomics models. Conclusions: The proposed radiomics model could accurately predict surgical vascularly inseparable TETs preoperatively and was shown to have a higher predictive value than the radiologists.

Integrated analysis reveals the microenvironment of non-small cell lung cancer and a macrophage-related prognostic model.

Background: In the treatment of non-small cell lung cancer (NSCLC), recent advances in immunotherapy have heralded a new era. Despite the success of immune therapy, a subset of patients persistently fails to respond. Therefore, to better improve the efficacy of immunotherapy and achieve the purpose of precision therapy, the research and exploration of tumor immunotherapy biomarkers have received much attention. Methods: Single-cell transcriptomic profiling was used to reveal tumor heterogeneity and the microenvironment in NSCLC. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was utilized to speculate the relative fractions of 22 infiltration immunocyte types in NSCLC. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used for the construction of risk prognostic models and predictive nomograms of NSCLC. Spearman's correlation analysis was employed to explore the relationship between risk score and tumor mutation burden (TMB) and immune checkpoint inhibitors (ICIs). Screening of chemotherapeutic agents in the high- and low-risk groups was performed with the "pRRophetic" package in R. Intercellular communication analysis was conducted using the "CellChat" package. Results: We found that most tumor-infiltrating immune cells were T cells and monocytes. We also found that there was a significant difference in the tumor-infiltrating immune cells and ICIs across different molecular subtypes. Further analysis showed that M0 and M1 mononuclear macrophages were significantly different in different molecular subtypes. The risk prediction model was shown to have to ability to accurately predict the prognosis, immune cell infiltration, and chemotherapy efficacy of patients in the high and low-risk groups. Finally, we found that the carcinogenic effect of migration inhibitory factor (MIF) is mediated by binding to CD74, CXCR4, and CD44 receptors involved in MIF cell signaling. Conclusions: We have revealed the tumor microenvironment (TME) of NSCLC through single-cell data analysis and constructed a prognosis model of macrophage-related genes. These results could provide new therapeutic targets for NSCLC.

Safety and feasibility of a modularized procedure for trans-subxiphoid robotic extended thymectomy.

BACKGROUND: The purpose of this study was to introduce an "eight-step modularized procedure (M-RET)" for trans-subxiphoid robotic extended thymectomy for patients with myasthenia gravis (MG). Its safety and feasibility were further verified in this study. MATERIALS AND METHODS: This retrospective study included 87 consecutive MG patients who underwent trans-subxiphoid robotic extended thymectomy at our institution between September 2016 and August 2021. According to different resection models, patients were divided into two groups: traditional trans-subxiphoid robotic extended thymectomy group (T-RET group) and eight-step modularized technique group (M-RET group). Baseline demographic characteristics and operation-related parameters were collected and compared between the two groups. RESULTS: There were 41 (47.1%) patients in the M-RET group and 46 (52.9%) patients in the T-RET group. The M-RET group resected a greater amount of mediastinal adipose tissues and required more dissection time (median and interquartile range: 135.0, 125.0 to 164.0 v. 120.0, 105.0 to 153.8, P = 0.006) compared with the T-RET group. There were no statistically significant differences in terms of the intraoperative blood loss, duration of chest drainage, length of hospital stay, and postoperative complications between the two groups. There was no mortality or conversion in each of the two groups and all patients recovered well upon discharge. CONCLUSION: The eight-step modularized technique of trans-subxiphoid robotic extended thymectomy was verified to be a safe, effective, radical procedure, which offers unique superiority over ectopic thymic tissue resection.

UCHL1 promotes cancer stemness in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a special kind of breast cancer with strong ability of invasion and metastasis. UCHL1 belongs to the ubiquitin carboxy-terminal hydrolase family and is found to be increased in a variety of malignancies, but its expression in TNBC is unknown. METHODS: First, we analyzed the expression of UCHL1 in 128 TNBC specimens and paired adjacent normal tissues from 17 TNBC patients undergoing curative resection by immunohistochemistry. Then, the relationship between UCHL1 and cancer stemness was investigated by cell flow cytometry, spheroid formation assays and western blot. Moreover, cell scratch assay and Transwell assays were performed to explore whether UCHL1 promotes the migration and invasion of TNBC cells. Finally, we constructed a xenografts model of TNBC cell lines to observe the effect of UCHL1 on tumorigenesis in vivo. RESULTS: UCHL1 was overexpressed in TNBC tissues and associated with poor prognosis. UCHL1 promoted stem cancer cells properties, including the percentage of CD44+/CD24- cells, sphere-forming ability and CSCs related markers. Furthermore, Scratch assay and Transwell assay proved that UCHL1 enhanced the migration and invasion of TNBC cells. The experimental results of xenografts model in nude mice showed that UCHL1 promoted tumorigenesis of TNBC in vivo. CONCLUSION: UCHL1 may play a role in the malignant progression of TNBC by maintaining the stemness and promoting cell invasion and is expected to become a potential therapeutic target for TNBC patients.

Rate-Dependent Hysteresis Modeling and Displacement Tracking Control Based on Least-Squares SVM for Axially Pre-Compressed Macro-Fiber Composite Bimorph.

The new axially pre-compressed macro-fiber composite bimorph (MFC-PBP) can produce large displacement and output power. However, it has the property of strong rate-dependent hysteresis nonlinearity, which challenges the displacement tracking control of morphing structures. In this paper, the least-squares support vector machine (LS-SVM) is applied to model the rate-dependent hysteresis of MFC-PBP. Compared with the predicated results of the series model of the Bouc-Wen model and Hammerstein model (BW-H), the LS-SVM model achieved higher predication accuracy and better generalization ability. Based on the LS-SVM hysteresis compensation model, with the support vector pruning, the displacement tracking feedforward compensator is obtained. In order to improve the displacement tracking accuracy, the LS-SVM feedforward compensator combined with the proportional and integral (PI) controller and the feedforward plus feedback control experiment is carried out on the displacement tracking of MFC-PBP. The test results show that the feedforward plus feedback displacement tracking control loop based on the LS-SVM model also has a higher displacement tracking accuracy than that based on the inverse model of BW-H.

Risk factors of wound infection after lung transplantation: a narrative review.

Background and Objective: The incidence of incision infection after lung transplantation is prominently high which affect the prognosis. Summarizing the risk factors related to incision infection after lung transplantation contribute to the control of incision infection by pre-controlling the risk factors. The objective is to summarize risk factors related to wound infection after lung transplantation. Methods: PubMed was used to research the literature relating to the risk factors to incision infection after lung transplantation through 1990 to 2022. The retrieval strategy were Medical Subject Heading (MeSH) terms combined entry terms. Two researchers conducted the literature retrieval independently. Two researchers independently evaluate the quality of the literature and summarize the indicators. Key Content and Findings: A total of 98 researches were collected from PubMed and 8 articles described the related risk factors of incision infection after lung transplantation. All of the 8 articles were retrospective studies, of which 4 articles were grouped by the delayed chest closure (DCC) execution and the other 4 articles were grouped by the surgical site infection (SSI) occurred. Two articles performed multivariate regression analysis to determine the independent risk factors of SSI after lung transplantation and the other 6 articles compared the SSI rate in different patients population. The integrated results showed that bronchoalveolar lavages (BALs), smoking status, body mass index (BMI), diabetes, operation duration, thoracic drainage tube placement time and DCC were related to the SSI after lung transplantation. Conclusions: BALs, smoking status, BMI, diabetes, operation duration, thoracic drainage tube placement time and DCC were related to the SSI after lung transplantation.

Application of a new one-dimensional deep convolutional neural network for intelligent fault diagnosis of rolling bearings.

As one of the key parts of rotary machine, the fault diagnosis and running condition monitoring of rolling bearings are of great importance for normal working and safe production of rotary machine. However, the traditional diagnosis approaches merely count on artificial feature extraction and domain expertise. Meanwhile, the existing convolutional neural networks (CNNs) have the problem of low fault recognition rates. This paper proposes a novel convolutional neural network with one-dimensional structure (ODCNN) for the automatical fault diagnosis of rolling bearings, which adopts six sets of convolutional and max-pooling layers to extract signal features and applies a flattening convolutional layer followed by two fully-connected layers for feature classification. The architectures of one-dimensional LeNet-5, AlexNet, and the proposed ODCNN are illustrated in detail, followed by the obtaining of training and testing samples, which is pre-processed by overlapping the vibration signals of rolling bearings. Finally, the classification experiment is carried out. The experimental results show that the ODCNN has higher fault diagnosis rates and can achieve high accuracy with load variant. Additionally, the extracted features of three CNNs are visualized, which illustrate that the new CNN has a better classification capacity.

Mannose shows antitumour properties against lung cancer via inhibiting proliferation, promoting cisplatin­mediated apoptosis and reducing metastasis.

It has been reported that mannose exerts antitumour effects against certain types of cancer. The present study was designed to evaluate whether mannose exerted potential anticancer effects on A549 and H1299 non­small cell lung cancer (NSCLC) cells in vitro, which has not been reported previously. A Cell Counting Kit­8 cell viability assay was used to assess the antiproliferative effects of mannose on NSCLC cells. Flow cytometry­based methods were used to evaluate the effects of mannose on the cell cycle distribution and cisplatin­mediated apoptosis of NSCLC cells. Transwell migration and invasion assays were conducted to examine whether mannose could inhibit the invasive abilities of NSCLC cells. The effects of mannose on the PI3K/AKT and ERK signalling pathways were explored through western blot analysis assessing the expression of phosphorylated (p)­AKT and p­ERK1/2. It was found that mannose showed potential anticancer effects against NSCLC cells in vitro by inhibiting proliferation, inducing G0/G1 cell cycle arrest, promoting cisplatin­induced apoptosis and decreasing the invasive abilities. These data indicate the potential anticancer properties of mannose and suggest the application of mannose­based therapies to treat NSCLC.

Effect of EGFR gene polymorphism on efficacy of chemotherapy combined with targeted therapy for non-small cell lung cancer in Chinese patients.

EGFR-TKI had become the first-line treatment of metastatic NSCLC and widely used in clinical. It was reported that there was difference in response rate between NSCLC patients with or without EGFR mutation. However, there was no relevant studies about the difference in clinical response among patients with different kinds of EGFR mutation. In this study, we recruited 464 patients with NSCLC between March 2014 and March 2015. Circulating tumor DNA (ctDNA) was isolated from plasma and identified EGFR gene mutations. Demographic characteristics, pathological data, safety and three-year survival were compared in patients with different EGFR gene mutations. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), disease control rate (DCR) and overall survival (OS). Among all the patients, the total mutation rate of EGFR gene was 45.04%, major occurred in 19 exon (40.19%) and 21 exon (48.80%), respectively. There was great difference in gender, smoking status, TNM stage among patients with 19 exon, 21 exon and other mutation of EGFR (All P < 0.05). The ORR (34.31% vs. 28.57%, 21.74%) and DCR (73.53% vs. 69.05%, 56.52%) in patients with 21 exon mutation was significantly higher than patients with 19 exon or other mutations. After three-year follow-up, the median PFS was 7.9 months in the 21 exon group, 6.4 months in the 19 exon group and 5.1 months in the other mutation group (P < 0.05). And the median OS in patients with EGFR 21 exon mutation was significantly higher than those of patients with EGFR 19 exon or other mutations. In conclusion, applied with chemotherapy and EGFR-TKI, Chinese NSCLC patients with EGFR gene 21 exon mutation could have better clinical response and long-term survival than those with other kinds of mutation.

Folate-receptor-positive circulating tumor cells as an efficacious biomarker for the diagnosis of small pulmonary nodules.

OBJECTIVE: The objective of this study is to investigate the clinical significance of folate-receptor-positive circulating tumor cells (FR+CTC) for the diagnosis of lung cancer, especially in early-stage patients. MATERIALS AND METHODS: A total of 72 lung cancer patients, including 31 with stage I diseases and two with stage 0 diseases, were enrolled in this study. Twenty-four patients with benign lung diseases and two healthy volunteers served as the control group. Three milliliters of peripheral blood were collected from each participant for FR+CTC analysis on enrollment. FR+CTC enumeration was performed using immunomagnetic leukocyte depletion and ligand-targeted polymerase chain reaction techniques. RESULTS: The study results revealed that using a cutoff value of 8.7 CTC Units/3 mL, the sensitivity, and specificity of FR+CTC for diagnosis of lung cancer were 81.94% and 73.08%, respectively. Such high sensitivity (74.19%) and specificity (73.08%) persisted even if only stage I lung cancer patients were retained in the analysis. In receiver operating characteristic analysis, the performance of FR+CTC (area under the curve = 0.8153) was superior to other clinical biomarkers such as carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments. In a subgroup analysis, patients with nodule size of >3 cm showed an improved sensitivity (88.46%); although, the specificity appeared to decrease (40%). All five patients with benign diseases in this subgroup had inflammatory diseases, indicating that large inflammatory nodules may also release FR -expressing cells into the circulatory system. CONCLUSION: FR+CTC is a reliable biomarker for the early diagnosis of small-sized lung cancer. Further study with larger sample size is required to assess the diagnostic efficiency of FR+CTC in patients with large nodule sizes.

Diagnostic performance of CTLA-4, carcinoembryonic antigen and CYFRA 21-1 for malignant pleural effusion.

OBJECTIVES: The diagnosis of malignant pleural effusion (MPE) remains a clinical challenge. As a negative regulator of T-cell activation, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has been associated with many malignant diseases. However, there is limited data about the relationship between CTLA-4 and MPE. The present study aims to investigate whether CTLA-4 levels may correlate with presence of MPE and to assess its potential diagnostic accuracy relative to that of the established markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1). METHODS: Pleural effusion samples were collected from 36 patients with MPE and 48 patients with benign pleural effusion (BPE). Pleural levels of CTLA-4 were measured by ELISA; levels of CEA and CYFRA 21-1, by electrochemiluminescence immunoassay. Receiver operating characteristic curves were calculated to evaluate the ability of CTLA-4, CEA and CYFRA 21-1 to differentiate MPE from BPE. RESULTS: Pleural levels of CTLA-4 were significantly higher in MPE than in BPE patients (471.73 ± 378.86 vs. 289.22 ± 173.67 pg/ml, p = 0.004). At a cut-off value of 351.25 pg/ml, the sensitivity and specificity of CTLA-4 in diagnosing MPE were 58.30% and 83.30%, respectively, and the area under the curve was 0.72. Pleural levels of CEA and CYFRA 21-1 were also higher in MPE. Using the combination of CTLA-4, CEA and CYFRA 21-1 increased diagnostic sensitivity to 88.89% and the area under the curve to 0.92. CONCLUSION: The results of this preliminary study suggest that increased levels of CTLA-4 correlate with MPE, and that CTLA-4 may have some diagnostic usefulness when used in combination with conventional tumor markers such as CEA and CYFRA 21-1. These results justify larger, more rigorous studies to validate our findings.

Ionothermal synthesis of Fe3O4 magnetic nanoparticles as efficient heterogeneous Fenton-like catalysts for degradation of organic pollutants with H2O2.

Fe3O4 magnetic nanoparticles (MNPs) are attractive heterogeneous Fenton-like catalysts for oxidative degradation of organic pollutants with H2O2. Herein highly efficient and stable Fe3O4 MNPs (Fe3O4-op-DES, ca. 10nm) were successfully prepared via a novel oxidative precipitation-combined ionothermal synthesis, which comprised oxidative precipitation of FeSO4·7H2O in choline chloride:2urea deep eutectic solvent. Among five different Fe3O4 particles tested, Fe3O4-op-DES MNPs exhibited the highest catalytic activity with the activation energy of 47.6kJmol-1 for degradation of Rhodamine B (RhB) with H2O2 under the same conditions (Fe3O4 dosage of 0.50gL-1, H2O2 concentration of 40mmolL-1, pH 6.4, 55°C, 2h). Fe3O4-op-DES MNPs were magnetically recoverable, and had good catalytic stability and recyclability without the need of regeneration (>98% degradation efficiency of RhB in 2h and pseudo-first-order rate constant of 0.0376min-1 after having been continuously running for 12h). The superior catalytic performance of Fe3O4-op-DES MNPs was attributed to the combination of multiple technologically important features, including the nanometer size, high Fe2+ content, large surface area, high density of surface active sites and stable crystal structure (no phase transformation, negligible iron leaching and particle aggregation after reaction). The wide applicability of Fe3O4-op-DES MNPs was also demonstrated by the degradation of four other organic pollutants.