Comparison of Postoperative Outcomes Between Near-Infrared Fluorescent Imaging-Guided Mediastinal Lymphadenectomy and Conventional Surgery for Esophageal Cancer.

BACKGROUND: The study aimed to evaluate the efficacy of using near-infrared fluorescent imaging (NIRF) imaging with indocyanine green as an intraoperative tool for achieving complete mediastinal lymph node (LN) resection. PATIENTS AND METHODS: Between September 2019 and July 2021, patients with potential for esophagectomy due to middle and lower thoracic esophageal cancer were enrolled in this study. All patients were scheduled for NIRF-guided mediastinal lymphadenectomy during esophageal cancer surgery and were appropriately assigned to the NIRF group. Patients who underwent esophagectomy between September 2017 and September 2019 were assigned to the historical control group upon satisfying the inclusion/exclusion criteria. Surgical outcomes and the number of removed LNs were compared between the two groups using 1:1 propensity score matching. RESULTS: Of 67 eligible patients, 59 patients were included in the NIRF group after postsurgical exclusions. The operative time was significantly shorter in the NIRF group than in the historical control group [180 (140-420) min versus 202 (137-338) min; P < 0.001]. The incidence of postoperative chylothorax and hoarseness were significantly lower in the NIRF group than in the historical control group (0% versus 10.2 %; P = 0.036, 3.4% versus 13.6%; P = 0.047). The number of dissected total LNs, mediastinal LNs, and negative LNs was significantly larger in the NIRF group than in the historical control group. The number of overall metastatic LNs and abdominal LNs was comparable between the two groups. CONCLUSIONS: NIRF imaging can assist in the thorough and complete mediastinal LNs dissections without increasing complications in patients undergoing esophagectomy.

Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.

Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies.

A digital in situ bone augmentation workflow for reconstructing the alveolar ridge outline using a modified shell technique.

The traditional shell technique is a practical method for augmenting horizontal and vertical alveolar bone defects. However, it has drawbacks, including increased morbidity in the donor site and imprecise harvesting of bone grafts. Instead of using a second surgical site, root areas at the defect site could be the in situ donor site. A digitally designed bone harvest guide was used for an in situ bone augmentation workflow, and the modified shell technique was planned and executed in the root area. This technique offered a controllable procedure which might enhance bone augmentation.

Malignant melanoma with liver, stomach, and duodenal metastasis.

Malignant melanoma (MM) is a common and highly invasive malignant tumor in clinical practice that is prone to occur in the skin and mucosa and prone to early metastasis. The common sites of metastasis are the liver, lungs, brain, etc. Metastatic gastrointestinal mucosa is relatively rare. Once metastasis occurs, the prognosis of patients is significantly worse. This article reports a case diagnosed as MM with liver, stomach, and duodenal metastasis by ultrasound-guided endoscopic puncture at Fengdu People's Hospital in Chongqing, with gastrointestinal discomfort as the initial symptom and a history of melanoma. Therefore, when a patient has a history of melanoma surgery and presents with digestive symptoms, it is necessary to consider the disease. Regular endoscopic screening should be performed, and early surgical treatment and postoperative chemotherapy combined with targeted therapy may improve patient prognosis and prolong patient survival.

Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives.

Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.

Radiomics Nomogram with Added Nodal Features Improves Treatment Response Prediction in Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter Study.

OBJECTIVE: We aimed to develop and validate a radiomics nomogram and determine the value of radiomic features from lymph nodes (LNs) for predicting pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: In this multicenter retrospective study, eligible participants who had undergone NCRT followed by radical esophagectomy were consecutively recruited. Three radiomics models (modelT, modelLN, and modelTLN) based on tumor and LN features, alone and combined, were developed in the training cohort. The radiomics nomogram was developed by incorporating the prediction value of the radiomics model and clinicoradiological risk factors using multivariate logistic regression, and was evaluated using the receiver operating characteristic curve, validated in two external validation cohorts. RESULTS: Between October 2011 and December 2018, 116 patients were included in the training cohort. Between June 2015 and October 2020, 51 and 27 patients from two independent hospitals were included in validation cohorts 1 and 2, respectively. The radiomics modelTLN performed better than the radiomics modelT for predicting pCR. The radiomics nomogram incorporating the predictive value of the radiomics modelTLN and heterogeneous after NCRT outperformed the clinicoradiological model, with an area under the curve (95% confidence interval) of 0.833 (0.765-0.894) versus 0.764 (0.686-0.833) [p = 0.088, DeLong test], 0.824 (0.718-0.909) versus 0.692 (0.554-0.809) [p = 0.012], and 0.902 (0.794-0.984) versus 0.696 (0.526-0.857) [p = 0.024] in all three cohorts. CONCLUSIONS: Radiomic features from LNs could provide additional value for predicting pCR in ESCC patients, and the radiomics nomogram provided an accurate prediction of pCR, which might aid treatment decision.

Effect of Intrathoracic or Cervical Anastomosis After Esophagectomy on Quality of Life.

PURPOSE: We aimed to perform serial quality-of-life (QoL) evaluations and comparisons in patients after esophagectomy with intrathoracic anastomosis (IA) or cervical anastomosis (CA). METHODS: Between November 2012 and March 2015, patients who underwent esophagectomy with IA or CA for mid-esophageal to distal esophageal or gastroesophageal junction cancer were followed up. QoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and esophagus-specific questionnaire (EORTC QLQ-OES18) before surgery, at discharge, and at 1, 6, 12, and 24 months after discharge. Linear mixed-effect models were used to assess the mean score differences (MDs) of each QoL scale between the two techniques, and changes in QoL over time. Potential confounders were adjusted. RESULTS: In total, 219 patients were analyzed (IA, n = 127; CA, n = 92). All patients' QoL decreased immediately after esophagectomy. Global QoL and most functioning and symptom scales exhibited a return to baseline levels within 2 years of discharge, except for physical functioning and several symptoms (dyspnea, diarrhea, dysphagia, and reflux). There was no difference in overall health score between the two groups (MD 2, 95% confidence interval [CI] - 1 to 6). Compared with IA, patients with CA reported more trouble with taste (MD - 12, 95% CI - 19 to - 4) and talking (MD - 11, 95% CI - 19 to 2) at discharge. No differences in long-term QoL were found between groups. CONCLUSIONS: CA was associated with more trouble with taste and talking in the short term than IA. The long-term QoL did not differ between the two approaches.

Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.

BACKGROUND: The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8+ T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36+CD8+ T cells in NSCLC. METHODS: Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage. RESULTS: Accumulation of CD36+CD8+ T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36+CD8+ T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36+CD8+ T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36+CD8+ T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8+ T cells by producing more GZMB and IFN-γ. CONCLUSION: CD36+CD8+ T cells exhibit impaired immune function and high infiltration of CD36+CD8+ T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients.

Evaluation of integrated modular teaching in Chinese ophthalmology trainee courses.

BACKGROUND: Before attending ophthalmology trainee courses in Zhongshan Ophthalmic Centre, the medical students from Sun Yat-sen University had finished two years of premedical education after the six-year medical courses including basic medical courses, clinical medical courses, clerkship, and research training in medical college. Integrated modular teaching using different problem-based teaching methods in ophthalmology was designed by the teaching steering committee of Zhongshan Ophthalmic Centre. This study aimed to evaluate the effectiveness and satisfaction scales of the integrated modular teaching among the trainee students. METHODS: A total of 100 medical students attending ophthalmology trainee courses in Zhongshan Ophthalmic Centre were enrolled and randomly allocated into 4 groups according to the teaching arrangement. The trainee courses consisted of several sessions delivered in multiple methods, such as "flipped classroom" session and team-based learning session. The pre- and post-class tests were delivered to evaluate the effectiveness of the integrated modular teaching. The satisfaction survey questionnaire was collected from all participants to investigate the degree of satisfaction. RESULTS: Compared with the first-day-test score, the total last-day-test score was significantly improved by a paired t-test (t = 3.288, P = 0.001). Nineteen students obtained a significant improvement in ranking increased by more than 10 in the last-day-test, whereas they failed to obtain a higher average score for daily performance than other students (t = 0.469, P = 0.654). According to the participant satisfaction questionnaires, these innovative teaching methods were considered as effective and satisfactory. CONCLUSIONS: Integrated modular teaching in ophthalmology trainee courses is effective and appreciated by the medical college students.

FHL2 activates ß-catenin/Wnt signaling by complexing with APC and TRIM63 in lung adenocarcinoma.

OBJECTIVES: Four and a half LIM domain 2 protein (FHL2) was reported to regulate the progression of various cancers and this study aimed to clarify the intrinsic mechanism of FHL2 facilitating the progression of lung adenocarcinoma. METHODS: In this study, bioinformatic analysis and immunohistochemistry staining were used to confirm the FHL2 levels in patients with lung adenocarcinoma. The potential influence of FHL2 on the biological function of lung adenocarcinoma cells was verified in vitro and in vivo. To uncover the potential mechanism contributing to the advance of lung adenocarcinoma, liquid chromatography‒mass spectrometry and immunoprecipitation assays were performed to detect the partners of FHL2. RESULTS: FHL2 levels were upregulated in lung adenocarcinoma and contributed to a dismal prognosis. Moreover, in vitro and in vivo assays suggested that genetic inhibition of FHL2 undermined the viability, migration and invasion of lung adenocarcinoma cells, while forced expression of FHL2 showed the opposite trend. Mechanistically, liquid chromatography‒mass spectrometry and coimmunoprecipitation assays revealed that FHL2 could function as a scaffold to enhance TRIM63-mediated ubiquitination of APC. The degradation of APC further stabilized ß-catenin and activated Wnt signaling pathway. CONCLUSION: Collectively, this study uncovered the underlying mechanism by which FHL2 regulates the biological characteristics of tumors and provided a novel target for lung adenocarcinoma treatment.

Establishment and validation of a clinicopathological prediction model for postoperative recurrence of stage IA lung adenocarcinoma.

Background: With the popularization of low-dose spiral computed tomography (CT), an increasing number of stage IA lung cancers have been discovered. Patients with stage IA lung adenocarcinoma who undergo radical surgical resection tend to have a favourable prognosis. However, A significant proportion of patients undergo postoperative recurrence and metastasis. The purpose of this study was to screen out the risk factors in patients with stage IA lung adenocarcinoma and establish a nomogram model to help clinicians identify high-risk patient groups. Methods: A nomogram was conducted based on a retrospective study of 731 patients with stage IA lung adenocarcinoma. Concordance index (C-index), clinical decision analysis, receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the nomogram. Survival curves were drawn by Kaplan-Meier method, and significance was determined by log-rank test. According to nomogram scores, the patients were divided into low- and high-risk subgroups. Results: The internal and external cohorts included 731 and 235 eligible patients. In univariate and multivariate analyses, the independent factors for recurrence-free survival (RFS) were all selected in the nomogram. C-indexes of the nomogram were 0.812 (95% confidence interval: 0.756-0.868) and 0.817 in the internal and external validation, respectively, showing that the prominent prediction performance was great. Nomogram scores showed that patients in the low-risk group (5-RFS rate, 0.797 to 0.99) had better RFS than patients in the high-risk group (5-RFS rate, 0.10 to 0.797) (P<0.001). Conclusions: A nomogram model was established that can be beneficial to evaluate RFS in patients with stage IA lung adenocarcinoma after curative resection. It can be of value in helping clinicians develop treatment strategies to improve patient survival.

Hypoxia-Mimicking Mediated Macrophage-Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvß3/Fe2+-Glycolysis-Inflammation.

Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti-fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro-inflammatory toxic metabolites, interfering with bone regeneration. Proper bio-elimination of erythrocytes is essential for an undisturbed bone regeneration process. Here, hypoxia-mimicking is applied to enhance macrophage-elimination of erythrocytes. The effect of macrophage-elimination of erythrocytes on the macrophage intracellular reaction, bone regenerative microenvironment, and bone regeneration outcome is investigated. Results show that the hypoxia-mimicking agent dimethyloxalylglycine successfully enhances erythrophagocytosis by macrophages in a dose-dependent manner primarily by up-regulating the expression of integrin αvß3. Increased phagocytosed erythrocytes then regulate macrophage intracellular Fe2+-glycolysis-inflammation, creating an improved bone regenerative microenvironment characterized by loose fibrin meshes with down-regulated local inflammatory responses in vivo, thus effectively promoting early osteogenesis and ultimate bone generation. Modulating macrophage-elimination of erythrocytes can be a promising strategy for eradicating erythrocyte-caused bone regeneration hindrance and offers a new direction for advanced biomaterial development focusing on the bio-elimination of erythrocytes.

Deep Learning for Automatic Gross Tumor Volumes Contouring in Esophageal Cancer Based on Contrast-Enhanced Computed Tomography Images: A Multi-Institutional Study.

PURPOSE: To develop and externally validate an automatic artificial intelligence (AI) tool for delineating gross tumor volume (GTV) in patients with esophageal squamous cell carcinoma (ESCC), which can assist in neo-adjuvant or radical radiation therapy treatment planning. METHODS AND MATERIALS: In this multi-institutional study, contrast-enhanced CT images from 580 eligible ESCC patients were retrospectively collected. The GTV contours delineated by 2 experts via consensus were used as ground truth. A 3-dimensional deep learning model was developed for GTV contouring in the training cohort and internally and externally validated in 3 validation cohorts. The AI tool was compared against 12 board-certified experts in 25 patients randomly selected from the external validation cohort to evaluate its assistance in improving contouring performance and reducing variation. Contouring performance was measured using dice similarity coefficient (DSC) and average surface distance. Additionally, our previously established radiomics model for predicting pathologic complete response was used to compare AI-generated and ground truth contours, to assess the potential of the AI contouring tool in radiomics analysis. RESULTS: The AI tool demonstrated good GTV contouring performance in multicenter validation cohorts, with median DSC values of 0.865, 0.876, and 0.866 and median average surface distance values of 0.939, 0.789, and 0.875 mm, respectively. Furthermore, the AI tool significantly improved contouring performance for half of 12 board-certified experts (DSC values, 0.794-0.835 vs 0.856-0.881, P = .003-0.048), reduced the intra- and interobserver variations by 37.4% and 55.2%, respectively, and saved contouring time by 77.6%. In the radiomics analysis, 88.7% of radiomic features from ground truth and AI-generated contours demonstrated stable reproducibility, and similar pathologic complete response prediction performance for these contours (P = .430) was observed. CONCLUSIONS: Our AI contouring tool can improve GTV contouring performance and facilitate radiomics analysis in ESCC patients, which indicates its potential for GTV contouring during radiation therapy treatment planning and radiomics studies.

Hierarchical Piezoelectric Composites for Noninvasive Continuous Cardiovascular Monitoring.

Continuous monitoring of blood pressure (BP) and multiparametric analysis of cardiac functions are crucial for the early diagnosis and therapy of cardiovascular diseases. However, existing monitoring approaches often suffer from bulky and intrusive apparatus, cumbersome testing procedures, and challenging data processing, hampering their applications in continuous monitoring. Here, a heterogeneously hierarchical piezoelectric composite is introduced for wearable continuous BP and cardiac function monitoring, overcoming the rigidity of ceramic and the insensitivity of polymer. By optimizing the hierarchical structure and components of the composite, the developed piezoelectric sensor delivers impressive performances, ensuring continuous and accurate monitoring of BP at Grade A level. Furthermore, the hemodynamic parameters are extracted from the detected signals, such as local pulse wave velocity, cardiac output, and stroke volume, all of which are in alignment with clinical results. Finally, the all-day tracking of cardiac function parameters validates the reliability and stability of the developed sensor, highlighting its potential for personalized healthcare systems, particularly in early diagnosis and timely intervention of cardiovascular disease.

Mass-Produced Skin-Inspired Piezoresistive Sensing Array with Interlocking Interface for Object Recognition.

E-skins, capable of responding to mechanical stimuli, hold significant potential in the field of robot haptics. However, it is a challenge to obtain e-skins with both high sensitivity and mechanical stability. Here, we present a bioinspired piezoresistive sensor with hierarchical structures based on polyaniline/polystyrene core-shell nanoparticles polymerized on air-laid paper. The combination of laser-etched reusable templates and sensitive materials that can be rapidly synthesized enables large-scale production. Benefiting from the substantially enlarged deformation of the hierarchical structure, the developed piezoresistive electronics exhibit a decent sensitivity of 21.67 kPa-1 and a subtle detection limit of 3.4 Pa. Moreover, an isolation layer is introduced to enhance the interface stability of the e-skin, with a fracture limit of 66.34 N/m. Furthermore, the e-skin can be seamlessly integrated onto gloves without any detachment issues. With the assistance of deep learning, it achieves a 98% accuracy rate in object recognition. We anticipate that this strategy will render e-skin with more robust interfaces and heightened sensing capabilities, offering a favorable pathway for large-scale production.

TP53 Mutations in Esophageal Squamous Cell Carcinoma.

The occurrence and development of esophageal cancer involve multiple genetic abnormalities that contribute to the malignant transformation of esophageal epithelial cells, followed by invasion and metastasis, leading to a poor outcome. Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal malignancy in East Asia, with approximately half of newly diagnosed ESCC cases occurring in China. The TP53 tumor suppressor gene mutation is one of the most common mutations in ESCC. TP53 mutations are observed even in the early phases of esophageal carcinogenesis. Normal functions of the p53 network are lost in cells of ESCC patients who harbor the mutant TP53 gene, inducing tumor development, radiation resistance, chemotherapy resistance, and immune suppression, promoting progression and metastasis, thereby resulting in an overall poor prognosis. Although clinical trials of several pharmacological compounds targeting mutational TP53 have been explored, novel approaches are still urgently required to improve the observed dismal survival. A better understanding of the role of the mutant TP53 gene in human ESCC might lead to the discovery of innovative targeted therapies to treat this malignancy.

Flexible Lead-Free Piezoelectric Ba0.94Sr0.06Sn0.09Ti0.91O3/PDMS Composite for Self-Powered Human Motion Monitoring.

Piezoelectric wearable electronics, which can sense external pressure, have attracted widespread attention. However, the enhancement of electromechanical coupling performance remains a great challenge. Here, a new solid solution of Ba1-xSrxSn0.09Ti0.91O3 (x = 0.00~0.08) is prepared to explore potential high-performance, lead-free piezoelectric ceramics. The coexistence of the rhombohedral phase, orthorhombic phase and tetragonal phase is determined in a ceramic with x = 0.06, showing enhanced electrical performance with a piezoelectric coefficient of d33~650 pC/N. Furthermore, Ba0.94Sr0.06Sn0.09Ti0.91O3 (BSST) is co-blended with PDMS to prepare flexible piezoelectric nanogenerators (PENGs) and their performance is explored. The effects of inorganic particle concentration and distribution on the piezoelectric output of the composite are systematically analyzed by experimental tests and computational simulations. As a result, the optimal VOC and ISC of the PENG (40 wt%) can reach 3.05 V and 44.5 nA, respectively, at 138.89 kPa, and the optimal sensitivity of the device is up to 21.09 mV/kPa. Due to the flexibility of the device, the prepared PENG can be attached to the surface of human skin as a sensor to monitor vital movements of the neck, fingers, elbows, spine, knees and feet of people, thus warning of dangerous behavior or incorrect posture and providing support for sports rehabilitation.