Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery.

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-ß1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-ß1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

Wet-adhesive γ-PGA/ε-PLL hydrogel loaded with EGF for tracheal epithelial injury repair.

Following the global COVID-19 pandemic, the incidence of tracheal epithelial injury is increasing. However, the repair of tracheal epithelial injury remains a challenge due to the slow renewal rate of tracheal epithelial cells (TECs). In traditional nebulized inhalation treatments, drugs are enriched in the lungs or absorbed into the blood, reducing drug concentration at the tracheal injury site. In this study, we prepared an epidermal growth factor (EGF)-loaded gamma-polyglutamic acid (γ-PGA)/epsilon-poly-L-lysine (ε-PLL) (PP) hydrogel (EGF@PP) to promote the repair of tracheal epithelial injury. Epidermal growth factor promotes the proliferation of TECs and enhances vascularization, thereby accelerating injury repair. The PP hydrogel exhibits outstanding wet adhesion, slow drug release, and antibacterial and anti-inflammatory properties, making it suitable for application in the airways and creating an environment conducive to epithelial repair. Here, we established a rabbit model of tracheal injury using a laser to destroy the tracheal epithelium and delivered EGF@PP powder to the injury site under fiberoptic bronchoscopy guidance. Our findings revealed that this was an effective therapeutic strategy for accelerating the repair of tracheal epithelial injury.

Cancer Burden Variations and Convergences in Globalization: A Comparative Study on the Tracheal, Bronchus, and Lung (TBL) and Liver Cancer Burdens Among WHO Regions from 1990 to 2019.

Lung cancer and liver cancer are the leading and third causes of cancer death, respectively. Both lung and liver cancer are with clear major risk factors. A thorough understanding of their burdens in the context of globalization, especially the convergences and variations among WHO regions, is useful in precision cancer prevention worldwide and understanding the changing epidemiological trends with the expanding globalization. The Global Burden of Disease (GBD) and WHO Global Health Observatory (GHO) database were analyzed to evaluate the burden metrics and risk factors of trachea, bronchus, and lung (TBL) cancer and liver cancer. Western Pacific Region (WPR) had the highest age-standardized incidence rate (ASIR) for both liver cancer (11.02 [9.62-12.61] per 100,000 population) and TBL cancer (38.82 [33.63-44.04] per 100,000 population) in 2019. Disability-adjusted life years (DALYs) for liver and TBL cancer elevated with the increasing sociodemographic index (SDI) level, except for liver cancer in WPR and TBL cancer in European Region (EUR). Region of the Americas (AMR) showed the biggest upward trends of liver cancer age-standardized rates (ASRs), as well as the biggest downward trends of TBL cancer ASRs, followed by Eastern Mediterranean Region (EMR). Alcohol use and smoking were the leading cause of liver and TBL cancer death in most WHO regions. Variances of ASRs for liver and TBL cancer among WHO memberships have been decreasing during the past decade. The homogenization and convergence of cancer burdens were also demonstrated in different agegroups and sexes and in the evolution of associated risk factors and etiology. In conclusion, our study reflects the variations and convergences in the liver and lung cancer burdens among the WHO regions with the developing globalization, which suggests that we need to be acutely aware of the global homogeneity of the disease burden that accompanies increasing globalization, including the global convergences in various populations, risk factors, and burden metrics.

Short- and medium-term outcomes of video-assisted thoracoscopic surgery versus thoracotomy for carinal lung resection combined with carina reconstruction in locally advanced non-small cell lung cancer patients.

BACKGROUND: The application of video-assisted thoracoscopic surgery (VATS) for complex carina surgeries in treating non-small cell lung cancer (NSCLC) patients with involved carina is controversial. This study compared short- and medium-term outcomes of VATS versus thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC, aiming to assess the potential benefit of VATS over thoracotomy for these patients. METHODS: A total of 37 consecutive NSCLC cases receiving VATS (n = 14) or thoracotomy (n = 23) for carinal lung resection with carina reconstruction from 2016 to 2021 were retrospectively identified. Baseline clinicopathological characteristics, perioperative outcomes, and survival profiles were investigated. RESULTS: Patients in the VATS and thoracotomy groups had comparable baseline clinicopathological characteristics (all p > 0.050). VATS decreased postoperative drainage volume compared with thoracotomy (1280 [1170-1510] vs. 1795 [1510-1905] mL, p = 0.012). Regarding surgical-related pains, VATS reduced numeric rating scale scores on the postoperative day 1 (4 [3, 4] vs. 5 [4, 5], p = 0.021) and day 2 (3 [3, 4] vs. 5 [3-5], p = 0.023) than thoracotomy. No difference was found between the VATS and thoracotomy groups in other perioperative outcomes, postoperative complications, and assessment of lymph nodes (LNs) and LN stations (all p > 0.050). Moreover, patients in the two groups had comparable 3-year disease-free survival (DFS), overall survival (OS), and recurrence and mortality patterns. Further subgroup and Cox hazards regression analyses also observed no difference in DFS or OS between the two groups. CONCLUSIONS: VATS reduced postoperative drainage volume and ameliorated surgical-related pain, and achieved comparable medium-term survival compared to thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC.

Multienzyme-Mimicking LaCoO3 Nanotrigger for Programming Cancer-Cell Pyroptosis.

Pyroptosis, a distinct paradigm of programmed cell death, is an efficient strategy against cancer by overcoming resistance to apoptosis. In this study, LaCoO3 (LCO) lanthanide-based nanocrystals with multienzyme characteristics are rationally designed and engineered to trigger the generation of cytotoxic reactive oxygen species (ROS) and the release of lanthanum ions, ultimately inducing lung cancer cell pyroptosis. The peroxidase- and oxidase-mimicking activities of LCO nanocrystals endow LCO with ROS production capacity in tumor tissues with an acidic pH and high hydrogen peroxide content. Concurrently, the LCO nanoenzyme exhibits catalase- and glutathione peroxidase-like activities, reversing the hypoxic microenvironment, destroying the activated antioxidant system of tumor cells, and amplifying the sensitivity of tumor cells to ROS. The use of ultrasound further accelerates the enzymatic kinetic rate. Most importantly, the La3+ ions released by LCO robustly destroy the lysosomal membrane, finally inducing canonical pyroptotic cell death, together with ROS. LCO-nanocrystal-triggered programmed cell pyroptosis amplifies the therapeutic effects both in vitro and in vivo, effectively restraining lung cancer growth and metastasis. This study paves a new avenue for the efficient treatment of lung cancer and metastasis through US-enhanced lanthanum-based nanoenzyme platforms and pyroptotic cell death.

Multi-scale characterization of tumor-draining lymph nodes in resectable lung cancer treated with neoadjuvant immune checkpoint inhibitors.

BACKGROUND: Regional lymph node (LN) acts as a pivotal organ for antitumor immunity. Paradoxically, tumor-draining LNs (TDLNs) are usually the first site of tumor metastasis in lung cancer. It is largely unknown about the association between the status of TDLNs and the response of primary tumor beds to immune checkpoint inhibitors (ICIs) in lung cancer patients. Also, studies characterizing the TDLNs in response to ICIs are scarce. METHODS: We characterized and compared the radiological, metabolic (18F-FDG) and pathologic responses between primary tumor beds and paired TDLNs (invaded/non-invaded) from 68 lung cancer patients who underwent neoadjuvant ICIs plus surgery. Additionally, we performed the spatial profiling of immune and non-immune cells within TDLNs using multiplexed immunofluorescence. Therapy responses (e.g., pathologic complete (pCR) or major response (MPR)) of primary lung tumor beds and paired TDLNs were investigated separately. FINDINGS: We observed that responses of TDLNs to ICIs markedly differ from their paired primary lung tumors regarding the radiological, metabolic (18F-FDG uptake), and pathologic alterations. Neoadjuvant ICIs therapy specifically decreased 18F-FDG-reflected metabolic activity in the primary tumor beds with pCR/MPR but not their TDLNs counterparts. Furthermore, the presence of invaded TDLNs was associated with poor pathologic responses in the matched primary tumor beds and predictive of rapid post-treatment tumor relapse. Spatial profiling demonstrated exclusion of T cell infiltrates within the metastatic lesions of invaded TDLNs, and diminished multiple immune and non-immune compositions in non-involved regions surrounding the metastatic lesions. INTERPRETATION: These results provide the first clinically-relevant evidence demonstrating unique response patterns of TDLNs under ICIs treatment and revealing the underappreciated association of TDLNs status with the response of their paired primary tumors to ICIs in lung cancer. FUNDING: This work was supported by the National Natural Science Foundation of China (82072570 to F. Yao; 82002941 to B. Sun), the excellent talent program of Shanghai Chest Hospital (to F.Y), the Basic Foundation Program for Youth of Shanghai Chest Hospital (2021YNJCQ2 to H.Yang), and the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212302 to F. Yao).

The improved success rate and reduced complications of a novel localization device vs. hookwire for thoracoscopic resection of small pulmonary nodules: a single-center, open-label, randomized clinical trial.

Background: In our previous study, we developed a 4-hook claw-suture localization device for pulmonary nodule resection, which acheived satifisfactory results. Following this, we conducted this single-center, open-label, randomized clinical trial to compare the success rate and complication rate of this novel localization device and currently widely-used hookwire. Methods: Patients with small pulmonary nodules (0.4-1 cm) who received preoperative localization and thoracoscopic resection at Shanghai Chest Hospital were randomly assigned (1:2 ratio, via computer-generated randomized numbers) to undergo localization using either a novel claw-suture system (claw group) or classical (hookwire group) localization device. The primary endpoint of this study was localization success rate, and the secondary endpoints included complications, localization-related time, and pain. Results: A total of 411 patients were randomly assigned to the claw group (n=136) or the hookwire group (n=275) before thoracoscopic resection of small pulmonary nodules and analyzed. Compared with the hookwire group, the claw group had a significantly higher success rate (133/136, 97.8% vs. 254/275, 92.4%, P=0.027), less asymptomatic hemorrhage (16.9% vs. 37.5%, P=0.003) and pleural reaction (0% vs. 5.1%, P=0.017), as well as better pain alleviation 10 min after localization (measured using the difference between two visual analog scale scores, 0.84±0.98 vs. 0.35±0.79, P<0.001). In contrast, the hookwire group was associated with a shorter localization procedure duration than the claw group (7.2±2.9 vs. 14.4±6.6 min, P<0.001). In the multiple localization subgroup, the claw group compared to the hookwire group also achieved higher success (32/33, 97.0% vs. 70/86, 81.4%) and less pleural reaction (0% vs. 16.3%). Conclusions: The new claw-suture localization device is superior to traditional hookwire, with a higher success rate, fewer complications, and better patient tolerance for preoperative localization of small pulmonary nodules. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900027346.

Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review.

Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.