Adapting to the acidic environment of the NP: RADA16-PLGA (TGF-ß3) induces chondrogenic differentiation of BMSCs.

Aim: RADA16-PLGA composite scaffolds constructed with simultaneous loading of BMSCs and TGF-ß3 and explored their ability for chondrogenic differentiation in vitro.Methods: The performance of the composite scaffolds is assessed by rheometer assay, electron microscopic structural observation and ELISA release assay. The biosafety of the composite scaffolds is assessed by cytocompatibility assay and cell migration ability. The chondrogenic differentiation ability of composite scaffolds is evaluated by Alisin blue staining, PCR and immunofluorescence staining.Results: The composite scaffold has a good ECM-like structure, the ability to control the release of TGF-ß3 and good biocompatibility. More importantly, the composite scaffolds can induce the differentiation of BMSCs to chondrocytes.Conclusion: Composite scaffolds are expected to enhance the endogenous NP repair process.

[Box: see text].

Chest wall resections for non-small cell lung cancer: a literature review.

Background and Objective: The development of early screening for lung cancer has led to improved overall survival in patients with non-small cell lung cancer (NSCLC). However, the management of NSCLC patients with resectable and potentially resectable chest wall invasion (CWI) requires attention. The purpose of this review is to summarize the role of surgery (chest wall resections) in NSCLC patients with CWI. Methods: A literature search and review from three databases (PubMed, Embase, and ScienceDirect) comprised the last 39 years. This review was focused on the treatment of NSCLC patients with CWI, mainly including the preoperative evaluation, principles of treatment and strategic decision-making, surgical complications, and prognostic factors. Key Content and Findings: Through the collection of relevant literature on NSCLC that invades the chest wall, this narrative review describes the actual role in clinical practice and future developments of chest wall resections. Preoperative treatment requires the multidisciplinary team (MDT) team to conduct accurate clinical staging of the patient and pay attention to the patient's lymph node status and rib invasion status. The successful implementation of chest wall resection and possible chest wall reconstruction requires refined individualized treatment based on the patient's clinical characteristics, supplemented by possible postoperative systemic treatment. Conclusions: Surgery plays an important role in treating NSCLC patients with CWI, and a collaborative, experienced MDT is an essential component of the successful treatment of CWI with lung cancer. In the future, more high-quality clinical research is needed to focus on CWI patients so that patients can receive more effective treatment options and better clinical prognosis.

Knowledge, attitude, and practice toward lung cancer risk among offspring of lung cancer patients: a cross-sectional study.

Lung cancer is intricately associated with genetic susceptibility, leading to familial clustering among affected individuals. This cross-sectional study aimed to assess the knowledge, attitude, and practice (KAP) toward lung cancer risk among the offspring of lung cancer patients. This study was conducted at Guangdong Provincial People's Hospital between April 2023 and August 2023. Participants' demographic characteristics and KAP toward lung cancer risk were collected through questionnaires. A total of 481 valid questionnaires were enrolled, with 243 (50.52%) males, and 242 (50.31%) aged > 40 years old. The mean scores for knowledge, attitude, and practice were 8.54 ± 2.60 (range: 0-13), 25.93 ± 3.16 (range: 7-35), and 17.47 ± 4.30 (range: 5-25), respectively. Structural equation modeling indicated that knowledge exerted a negative direct effect on attitude (ß = - 0.417, P = 0.006) but a positive direct effect on practice (ß = 0.733, P = 0.025). Additionally, attitudes displayed a negative direct effect on practice (ß = - 1.707, P = 0.002). In conclusion, offspring of lung cancer patients exhibited insufficient knowledge, positive attitude, and suboptimal practice toward lung cancer risk.

Robotic-assisted extended thymectomy for large resectable thymoma: 21 years' experience.

OBJECTIVE: This study aims to evaluate the perioperative and midterm oncological outcomes of robotic-assisted thoracic surgery extended thymectomy for patients with large resectable thymomas compared with small thymomas. METHODS: This retrospective single-center study included 204 patients with thymomas who underwent robotic-assisted thoracic surgery extended thymectomy between January 2003 and February 2024. Patients were divided into 2 groups based on the thymoma size (5-cm threshold). RESULTS: The study comprised 114 patients (55.9%) in the small thymoma group and 90 patients (44.1%) in the large thymoma group. No significant differences were found between the groups regarding gender, age, proportion of elderly patients, or pathologic high-risk classifications. Apart from a longer operative time (P = .009) in the large thymoma group, no differences were observed between the 2 groups regarding surgical parameters and postoperative outcomes. No deaths occurred within 30 days in either group. During a median follow-up of 61.0 months (95% CI, 48.96-73.04), 4 patients experienced recurrence (1.96%). No significant differences in the 5-year overall survival (P = .25) or recurrence-free survival (P = .43) were observed between groups. CONCLUSIONS: Robotic-assisted thoracic surgery extended thymectomy is technically feasible, safe, and effective for treating large resectable thymomas. Moreover, midterm outcomes for patients with completely resected large thymomas were comparable to those with small thymomas during a median follow-up period of up to 5 years.

Recommendations for broadening eligibility criteria in esophagus cancer clinical trials: the mortality disparity of esophagus cancer as a first or second primary malignancy.

Background: Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). Methods: We included primary esophagus cancer patients diagnosed from 1975 to 2019 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, gender, tumor stage and other demographic and clinical characteristics. Results: A total of 74,521 and 14,820 patients were identified as esophagus-1 and esophagus-2 respectively. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but with similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Conclusions: Esophagus-2 patients should not be entirely excluded from clinical trial and a 3-year exclusion window is suggested. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy.

Early patient-reported outcomes after robotic-assisted versus video-assisted thoracoscopic lobectomy.

BACKGROUND: Robotic-assisted thoracoscopic surgery (RATS) can achieve traditional clinical outcomes comparable to those of video-assisted thoracoscopic surgery (VATS). However, patient-reported outcomes (PROs) during the early period after RATS and VATS remain unclear. This study aimed to utilize longitudinal electronic PRO (ePRO) assessments to evaluate symptom burden and functional status between these approaches from patients' perspective. METHODS: This study comprised patients who underwent lobectomy via RATS or VATS for non-small cell lung cancer. We collected multiple-time-point PROs data from the prospective longitudinal study via an ePRO system. Symptom severity and function status were assessed using the perioperative symptom assessment for patients undergoing lung surgery and were analyzed between groups using linear mixed-effects models. RESULTS: Of the 164 patients, 42 underwent RATS and 122 underwent VATS. After propensity score matching (PSM), 42 RATS and 84 VATS exhibited similar baseline characteristics. During the 7-day postoperative period, participants underwent RATS reported milder pain (p = 0.014), coughing (p < 0.001), drowsiness (p = 0.001), and distress (p = 0.045) compared with those underwent VATS. Moreover, participants in RATS group showed less functional interference with walking (p < 0.001) and general activity (p < 0.001). RATS exhibited a shorter postoperative hospitalization (p = 0.021) but higher hospital cost (p < 0.001). Meanwhile, short-term clinical outcomes of operative time, dissected lymph node stations, chest tube drainage, and postoperative complication rates were comparable. CONCLUSION: PROs are important metrics for assessing patients' recovery after lobectomy. Compared with VATS, RATS may induce less symptom burden and better functional status for patients in the early postoperative period.

Pan-cancer analysis for the prognostic and immunological role of CD47: interact with TNFRSF9 inducing CD8 + T cell exhaustion.

PURPOSE: The research endeavors to explore the implications of CD47 in cancer immunotherapy effectiveness. Specifically, there is a gap in comprehending the influence of CD47 on the tumor immune microenvironment, particularly in relation to CD8 + T cells. Our study aims to elucidate the prognostic and immunological relevance of CD47 to enhance insights into its prospective utilities in immunotherapeutic interventions. METHODS: Differential gene expression analysis, prognosis assessment, immunological infiltration evaluation, pathway enrichment analysis, and correlation investigation were performed utilizing a combination of R packages, computational algorithms, diverse datasets, and patient cohorts. Validation of the concept was achieved through the utilization of single-cell sequencing technology. RESULTS: CD47 demonstrated ubiquitous expression across various cancer types and was notably associated with unfavorable prognostic outcomes in pan-cancer assessments. Immunological investigations unveiled a robust correlation between CD47 expression and T-cell infiltration rather than T-cell exclusion across multiple cancer types. Specifically, the CD47-high group exhibited a poorer prognosis for the cytotoxic CD8 + T cell Top group compared to the CD47-low group, suggesting a potential impairment of CD8 + T cell functionality by CD47. The exploration of mechanism identified enrichment of CD47-associated differentially expressed genes in the CD8 + T cell exhausted pathway in multiple cancer contexts. Further analyses focusing on the CD8 TCR Downstream Pathway and gene correlation patterns underscored the significant involvement of TNFRSF9 in mediating these effects. CONCLUSION: A robust association exists between CD47 and the exhaustion of CD8 + T cells, potentially enabling immune evasion by cancer cells and thereby contributing to adverse prognostic outcomes. Consequently, genes such as CD47 and those linked to T-cell exhaustion, notably TNFRSF9, present as promising dual antigenic targets, providing critical insights into the field of immunotherapy.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

Disruption of the rice ALS1 localized in chloroplast causes seedling-lethal albino phenotype.

Chloroplasts are the organelles responsible for photosynthesis and regulate normal plant growth. Although translation elongation factors play important roles in chloroplast development, functional studies of chloroplast translation elongation factors in higher plants remain very sparse. Here, we obtained a rice mutant exhibiting seedling-lethal albino phenotype and named it albino and lethal seedling 1 (als1). Consistently, low content of photosynthetic pigments, malformed chloroplasts and defective photosynthesis were observed in als1 mutant leaves. Map-based cloning experiment showed that als1 mutant had a T base insertion in Os02g0595700, causing a frame shift and premature stop codon. ALS1 encoded a GTP-binding protein EF-Tu, which acts as a translation elongation factor in chloroplast protein translation. ALS1 was found to be expressed throughout plant with highest expression level in young leaves. Moreover, ALS1 was located in chloroplast, whereas the truncated als1 could not normally be located in chloroplast. Additionally, the ALS1 mutation significantly influenced the expression of downstream genes, such as genes relevant to chlorophyll biosynthesis, photosynthesis as well as chloroplast development. These results show that ALS1 acts as a key regulator of chloroplast development and plant growth.

KD_ConvNeXt: knowledge distillation-based image classification of lung tumor surgical specimen sections.

Introduction: Lung cancer is currently among the most prevalent and lethal cancers in the world in terms of incidence and fatality rates. In clinical practice, identifying the specific subtypes of lung cancer is essential in diagnosing and treating lung lesions. Methods: This paper aims to collect histopathological section images of lung tumor surgical specimens to construct a clinical dataset for researching and addressing the classification problem of specific subtypes of lung tumors. Our method proposes a teacher-student network architecture based on a knowledge distillation mechanism for the specific subtype classification of lung tumor histopathological section images to assist clinical applications, namely KD_ConvNeXt. The proposed approach enables the student network (ConvNeXt) to extract knowledge from the intermediate feature layers of the teacher network (Swin Transformer), improving the feature extraction and fitting capabilities of ConvNeXt. Meanwhile, Swin Transformer provides soft labels containing information about the distribution of images in various categories, making the model focused more on the information carried by types with smaller sample sizes while training. Results: This work has designed many experiments on a clinical lung tumor image dataset, and the KD_ConvNeXt achieved a superior classification accuracy of 85.64% and an F1-score of 0.7717 compared with other advanced image classification methods.

Biomimetic Hydrogel Applications and Challenges in Bone, Cartilage, and Nerve Repair.

Tissue engineering and regenerative medicine is a highly sought-after field for researchers aiming to compensate and repair defective tissues. However, the design and development of suitable scaffold materials with bioactivity for application in tissue repair and regeneration has been a great challenge. In recent years, biomimetic hydrogels have shown great possibilities for use in tissue engineering, where they can tune mechanical properties and biological properties through functional chemical modifications. Also, biomimetic hydrogels provide three-dimensional (3D) network spatial structures that can imitate normal tissue microenvironments and integrate cells, scaffolds, and bioactive substances for tissue repair and regeneration. Despite the growing interest in various hydrogels for biomedical use in previous decades, there are still many aspects of biomimetic hydrogels that need to be understood for biomedical and clinical trial applications. This review systematically describes the preparation of biomimetic hydrogels and their characteristics, and it details the use of biomimetic hydrogels in bone, cartilage, and nerve tissue repair. In addition, this review outlines the application of biomimetic hydrogels in bone, cartilage, and neural tissues regarding drug delivery. In particular, the advantages and shortcomings of biomimetic hydrogels in biomaterial tissue engineering are highlighted, and future research directions are proposed.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

BACKGROUND: Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. METHODS: A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. RESULTS: The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). CONCLUSION: A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

Pretreatment radiomic biomarker for immunotherapy responder prediction in stage IB-IV NSCLC (LCDigital-IO Study): a multicenter retrospective study.

BACKGROUND: The predictive efficacy of current biomarker of immune checkpoint inhibitors (ICIs) is not sufficient. This study investigated the causality between radiomic biomarkers and immunotherapy response status in patients with stage IB-IV non-small cell lung cancer (NSCLC), including its biological context for ICIs treatment response prediction. METHODS: CT images from 319 patients with pretreatment NSCLC receiving immunotherapy between January 2015 and November 2021 were retrospectively collected and composed a discovery (n=214), independent validation (n=54), and external test cohort (n=51). A set of 851 features was extracted from tumorous and peritumoral volumes of interest (VOIs). The reference standard is the durable clinical benefit (DCB, sustained disease control for more than 6 months assessed via radiological evaluation). The predictive value of combined radiomic signature (CRS) for pathological response was subsequently assessed in another cohort of 98 patients with resectable NSCLC receiving ICIs preoperatively. The association between radiomic features and tumor immune landscape on the online data set (n=60) was also examined. A model combining clinical predictor and radiomic signatures was constructed to improve performance further. RESULTS: CRS discriminated DCB and non-DCB patients well in the training and validation cohorts with an area under the curve (AUC) of 0.82, 95% CI: 0.75 to 0.88, and 0.75, 95% CI: 0.64 to 0.87, respectively. In this study, the predictive value of CRS was better than programmed cell death ligand-1 (PD-L1) expression (AUC of PD-L1 subset: 0.59, 95% CI: 0.50 to 0.69) or clinical model (AUC: 0.66, 95% CI: 0.51 to 0.81). After combining the clinical signature with CRS, the predictive performance improved further with an AUC of 0.837, 0.790 and 0.781 in training, validation and D2 cohorts, respectively. When predicting pathological response, CRS divided patients into a major pathological response (MPR) and non-MPR group (AUC: 0.76, 95% CI: 0.67 to 0.81). Moreover, CRS showed a promising stratification ability on overall survival (HR: 0.49, 95% CI: 0.27 to 0.89; p=0.020) and progression-free survival (HR: 0.43, 95% CI: 0.26 to 0.74; p=0.002). CONCLUSION: By analyzing both tumorous and peritumoral regions of CT images in a radiomic strategy, we developed a non-invasive biomarker for distinguishing responders of ICIs therapy and stratifying their survival outcome efficiently, which may support the clinical decisions on the use of ICIs in advanced as well as patients with resectable NSCLC.

Radiation-sensitive genetic prognostic model identifies individuals at risk for radiation resistance in head and neck squamous cell carcinoma.

BACKGROUND: The advantages of radiotherapy for head and neck squamous cell carcinoma (HNSCC) depend on the radiation sensitivity of the patient. Here, we established and verified radiological factor-related gene signature and built a prognostic risk model to predict whether radiotherapy would be beneficial. METHODS: Data from The Cancer Genome Atlas, Gene Expression Omnibus, and RadAtlas databases were subjected to LASSO regression, univariate COX regression, and multivariate COX regression analyses to integrate genomic and clinical information from patients with HNSCC. HNSCC radiation-related prognostic genes were identified, and patients classified into high- and low-risk groups, based on risk scores. Variations in radiation sensitivity according to immunological microenvironment, functional pathways, and immunotherapy response were investigated. Finally, the expression of HNSCC radiation-related genes was verified by qRT-PCR. RESULTS: We built a clinical risk prediction model comprising a 15-gene signature and used it to divide patients into two groups based on their susceptibility to radiation: radiation-sensitive and radiation-resistant. Overall survival was significantly greater in the radiation-sensitive than the radiation-resistant group. Further, our model was an independent predictor of radiotherapy response, outperforming other clinical parameters, and could be combined with tumor mutational burden, to identify the target population with good predictive value for prognosis at 1, 2, and 3 years. Additionally, the radiation-resistant group was more vulnerable to low levels of immune infiltration, which are significantly associated with DNA damage repair, hypoxia, and cell cycle regulation. Tumor Immune Dysfunction and Exclusion scores also suggested that the resistant group would respond less favorably to immunotherapy. CONCLUSIONS: Our prognostic model based on a radiation-related gene signature has potential for application as a tool for risk stratification of radiation therapy for patients with HNSCC, helping to identify candidates for radiation therapy and overcome radiation resistance.

Self-assembling peptide RADA16: a promising scaffold for tissue engineering and regenerative medicine.

RADA16 is a peptide-based biomaterial whose acidic aqueous solution spontaneously forms an extracellular matrix-like 3D structure within seconds upon contact with physiological pH body fluids. Meanwhile, its good biocompatibility, low immunogenicity, nontoxic degradation products and ease of modification make it an ideal scaffold for tissue engineering. RADA16 is a good delivery vehicle for cells, drugs and factors. Its shear thinning and thixotropic properties allow it to fill tissue voids by injection and not to swell. However, the weaker mechanical properties and poor hydrophilicity are troubling limitations of RADA16. To compensate for this limitation, various functional groups and polymers have been designed to modify RADA16, thus contributing to its scope and progress in the field of tissue engineering.

Correlation of event-related potentials N170 with dysfunctional attitudes in patients with major depressive disorder.

BACKGROUND: Cognitive impairment frequently accompanies first-episode major depressive disorder (MDD) in patients. Early detection and intervention for cognitive impairment can enhance the quality of life for individuals with depressive disorders. Impaired emotion recognition may serve as an initial manifestation of cognitive impairment in these patients. This study examines the characteristics of event-related potentials N170 and dysfunctional attitudinal questionnaire total scores, as well as each factor and their correlation, revealing characteristic electroencephalogram (EEG) changes associated with cognitive impairment in first-episode MDD patients. METHOD: A total of 88 patients experiencing first-episode MDD and 29 healthy volunteers from the same period participated in the study. They underwent event-related potential N170 measures to assess mood recognition function, the 17-item Hamilton depression scale (HAMD-17) to evaluate the severity of depressive disorder, and the Dysfunctional Attitudes Scales(DAS) to appraise cognitive function. RESULT: The dysfunctional attitude questionnaire's total score and each factor score were higher in the MDD group compared to the healthy control (HC) group. The MDD group exhibited lower amplitudes than the HC group at CZ, PZ, POZ, P7, PO7, P8, and PO8 electrode points. A correlation was identified between the P7 and PO7 electrode points of the event-related potential N170 and cognitive function. LIMITATION: This study solely considered neutral face emotional stimuli and did not account for depressive disorder subtypes. CONCLUSION: Differences were observed between the MDD and HC groups in cognitive function and N170 amplitude in the central brain region (CZ, PZ, POZ), left posterior temporal region (P7), left occipitotemporal region (PO7), right posterior temporal region (P8), and right occipitotemporal region (PO8). Additionally, a correlation was found between N170 latency in the left posterior temporal region of the brain (P7) and the left occipitotemporal region (PO7) with cognitive function.

A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy.

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

Early and Persistent Dysphagia Relief Predicts Tumor Response in Esophageal Squamous Cell Carcinoma Patients Treated with Immunochemotherapy.

BACKGROUND: In this prospective study, we aimed to investigate the role of patient-reported dysphagia relief in predicting pathological tumor responses to neoadjuvant immunochemotherapy (NAIC) in locally advanced esophageal squamous cell carcinoma (ESCC) patients. METHODS: This study was designed as a multi-center, prospective study including ESCC patients who received NAIC in the discovery and validation cohorts. The patients' responses to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES 18 and QLQ-C30 were collected at multiple time points. Subsequent time point-intensive esophageal cancer-specific dysphagia trajectories were depicted using growth mixture modeling (GMM) analysis. Furthermore, univariate and multivariate binary logistic regression was used to assess the independent predictors for pathological tumor responses. RESULTS: A total of 120 patients from the discovery cohort and 42 patients from the validation cohort were included in the analysis. In the discovery cohort, 19 (22.9%) of the 83 patients achieved pCR status. In the independent validation cohort, 24 patients underwent surgery, and 9 (37.5%) patients achieved pCR status. Trajectory analysis showed that, in the pCR group, the beginning of rapid declines in the slope occurred on days 3, 6, and 9. Further multivariate analysis showed that the degree of dysphagia relief (△dysphagia%) was the only significant independent predictor for pCR status (OR = 3.267, 95% CI 1.66-6.428, P < 0.001). The AUC value for △dysphagia% was 0.961 (95% CI: 0.922-0.999, P < 0.001). CONCLUSION: The current study demonstrated that a longitudinal patient-reported outcome (PRO) was an easily obtained, cost-effective, and noninvasive tool for predicting tumor responses to neoadjuvant immunochemotherapy.