Predictive value of PD-L1 and TMB for short-term efficacy prognosis in non-small cell lung cancer and construction of prediction models.

Objective: To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated. Methods: A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model. Results: The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model. Conclusion: PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.

Combining Multiple Photosensitizer Modules into One Supramolecular System for Synergetic Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT), as an emerging cancer treatment, requires the development of highly desirable photosensitizers (PSs) with integrated functional groups to achieve enhanced therapeutic efficacy. Coordination-driven self-assembly (CDSA) would provide an alternative approach for combining multiple PSs synergistically. Here, we demonstrate a simple yet powerful strategy of combining conventional chromophores (tetraphenylethylene, porphyrin, or Zn-porphyrin) with pyridinium salt PSs together through condensation reactions, followed by CDSA to construct a series of novel metallo-supramolecular PSs (S1-S3). The generation of reactive oxygen species (ROS) is dramatically enhanced by the direct combination of two different PSs, and further reinforced in the subsequent ensembles. Among all the ensembles, S2 with two porphyrin cores shows the highest ROS generation efficiency, specific interactions with lysosome, and strong emission for probing cells. Moreover, the cellular and living experiments confirm that S2 has excellent PDT efficacy, biocompatibility, and biosafety. As such, this study will enable the development of more efficient PSs with potential clinical applications.

Right upper lobe segmentectomy and subsegmentectomy guided by classification pattern of peripheral segmental veins.

Background: Studies have analyzed the simplified branching pattern of peripheral segmental veins and developed a standardized approach for intersegmental vein identification in the right upper lobe (RUL). However, the identification approach of intersubsegmental veins has not been reported. This study aimed to supplement the identification approach of intersubsegmental veins and the classification pattern of peripheral segmental veins by using three-dimensional computed tomography bronchography and angiography (3D-CTBA). Materials and methods: A total of 600 patients with ground glass opacity (GGO) who had undergone 3D-CTBA preoperatively at Hebei General Hospital between September 2020 and September 2022 were used for the retrospective study. We reviewed the anatomical variations of RUL veins in these patients using 3D-CTBA images. Results: According to the anatomical position, the peripheral segmental veins structures of RUL were classified into five categories: "Iab type of anterior with central vein" (256/600, 42.7%), "Ib type of anterior with central vein" (166/600, 27.7%), "Central vein type" (38/600, 6.3%), "Anterior vein type" (81/600, 13.5%), "Right top pulmonary vein type" (57/600, 9.5%). The approach for intersegmental vein and intersubsegmental veins identification was divided into five types: anterior approach, posterobronchial approach, central vein approach, V2t approach, and intermediate bronchus posterior surface approach. Conclusions: The classification pattern of peripheral segmental veins should find wide application. Further, approaches identifying intersegmental veins and intersubsegmental veins may help thoracic surgeons perform safe and accurate RUL segmentectomy.

The role of extracellular vesicles in the development of nasopharyngeal carcinoma and potential clinical applications.

BACKGROUND: Extracellular vesicles (EVs) can be secreted by a wide variety of cells, including tumor cells, and contain some bioactive molecules from the source cells. Therefore, they can potentially be used as biomarkers for early diagnosis of tumors and for tumor therapy. In addition, EVs can affect the features of target cells and participate in regulating the development process of tumors. METHODS: A literature review was conducted to elucidate the role of extracellular vesicles in the progression and treatment of nasopharyngeal carcinoma. RESULTS: In this review, we discuss the molecular mechanisms of cell proliferation, angiogenesis, epithelial-mesenchymal transformation and metastasis, immune response, and chemo-radiotherapy resistance that are induced by EVs. We also reviewed the potential applications of EVs as biomarkers, therapeutic agents, and carriers so as to determine new directions for the early diagnosis and targeted therapy of nasopharyngeal carcinoma. The application limitations have also been discussed in this review, further work is needed to ensure optimal outcomes for patients. CONCLUSION: Although the roles of extracellular vesicles in the progression of nasopharyngeal carcinoma have been summarized, some aspects are still unclear and need to be further studied. In addition, the applications of extracellular vesicles in the treatment of nasopharyngeal carcinoma still need to optimize conditions to produce better therapeutic outcomes for patients with nasopharyngeal carcinoma.

Analysis of bronchovascular patterns in the left superior division segment to explore the relationship between the descending bronchus and the artery crossing intersegmental planes.

Background: A comprehensive understanding of the anatomical variations in the pulmonary bronchi and arteries is particularly essential to the implementation of safe and precise left superior division segment (LSDS) segmentectomy. However, no report shows the relationship between the descending bronchus and the artery crossing intersegmental planes. Thus, the purpose of the present study was to analyze the branching pattern of the pulmonary artery and bronchus in LSDS using three-dimensional computed tomography bronchography and angiography (3D-CTBA) and to explore the associated pulmonary anatomical features of the artery crossing intersegmental planes. Materials and methods: The 3D-CTBA images of 540 cases were retrospectively analyzed. We reviewed the anatomical variations of the LSDS bronchus and artery and assorted them according to different classifications. Results: Among all 540 cases of 3D-CTBA, there were 16 cases (44.4%) with lateral subsegmental artery crossing intersegmental planes (AX3a), 20 cases (55.6%) Without AX3a in the descending B3a or B3 type, and 53 cases (10.5%) with AX3a, 451 cases (89.5%) Without AX3a in the Without the descending B3a or B3 type. This illustrated that the AX3a was more common in the descending B3a or B3 type (P < 0.005). Similarly, there were 69 cases (36.1%) with horizontal subsegmental artery crossing intersegmental planes (AX1 + 2c), 122 cases (63.9%) Without AX1 + 2c in the descending B1 + 2c type, and 33 cases (9.5%) with AX1 + 2c, 316 cases (90.5%) Without AX1 + 2c in the Without the descending B1 + 2c type. Combinations of the branching patterns of the AX1 + 2c and the descending B1 + 2c type were significantly dependent (p < 0.005). The combinations of the branching patterns of the AX1 + 2c and the descending B1 + 2c type were frequently observed. Conclusions: This is the first report to explore the relationship between the descending bronchus and the artery crossing intersegmental planes. In patients with the descending B3a or B3 type, the incidence of the AX3a was increased. Similarly, the incidence of the AX1 + 2c was increased in patients with the descending B1 + 2c type. These findings should be carefully identified when performing an accurate LSDS segmentectomy.

Analysis of variations in the bronchovascular pattern of the lingular segment to explore the correlations between the lingular segment artery and left superior division veins.

Background: With the development of anatomical segmentectomy, the thoracic surgeons must master the anatomical variations of the pulmonary bronchi and vessels. However, there are only a few reports showing anatomic variations of the lingular segment (LS) using three-dimensional computed tomography bronchography and angiography (3D-CTBA). Thus, the present study aimed to analyze the bronchovascular patterns of the LS and explore the correlation between the lingular segment artery (LSA) and left superior division veins (LSDV). Materials and methods: The 3D-CTBA data of the left upper lobe (LUL) were collected from patients who had undergone lobectomy or segmentectomy at Hebei General Hospital between October 2020 and October 2022. We reviewed the clinical characteristics and variations in bronchi and pulmonary vessels and grouped them according to different classifications. Results: Among all 540 cases of 3D-CTBA, the branching patterns of LSA included 369 (68.3%) cases with the interlobar origin, 126 (23.3%) cases with the interlobar and mediastinal origin, and 45 (8.3%) cases with the mediastinal origin. The branching pattern of LSDV could be classified into three forms: Semi-central vein type (345/540, 63.9%), Non-central vein type (76/540, 14.1%), and Central vein type (119/540, 22.0%). There were 51 cases (9.4%) with Non-central vein type, 50 cases (9.3%) with Central vein type, 268 cases (49.6%) with Semi-central vein type in the interlobar type, and 7 cases (1.3%) with Non-central vein type, 9 cases (1.7%) with Central vein type, 29 cases (5.4%) with Semi-central vein type in the mediastinal type. Moreover, the Non-central vein type, the Central vein type, and the Semi-central vein type accounted for 18 (3.3%), 60 (11.1%), and 48 (8.9%) in the interlobar and mediastinal type. Combinations of the branching patterns of the LSA and LSDV were significantly dependent (p < 0.005). The combinations of the interlobar and mediastinal type with the Central vein type, and the interlobar type and the mediastinal type with the Semi-central vein type were frequently observed. Conclusions: This study found the relationship between the LSA and LSDV and clarified the bifurcation patterns of the bronchovascular in the LS. Our data can be used by thoracic surgeons to perform safe and precise LS segmentectomy.

The detailed classification of the interlobar artery and the artery crossing intersegmental planes in the right upper lobe.

Background: With the prevalence of three-dimensional computed tomography bronchography and angiography (3D-CTBA) and the development of anatomical segmentectomy, several studies have analyzed the branching patterns of peripheral segmental arteries in the right upper lobe (RUL). Nevertheless, the detailed classification of the branching patterns of the interlobar artery and the artery crossing intersegmental planes remains unknown. Thus, we conducted a retrospective study to analyze the variations of the interlobar artery and the artery crossing intersegmental planes in the RUL using 3D-CTBA. Materials and methods: A total of 600 patients with ground-glass opacity (GGO) who had undergone 3D-CTBA preoperatively at Hebei General Hospital between September 2020 and September 2022 were used for the retrospective study. We reviewed the anatomical variations of the RUL arteries in these patients using 3D-CTBA images. Results: The branching patterns of the RUL artery were classified into the following four categories: trunk superior (Tr. sup), Tr. sup + interlobar artery, Tr. sup + trunk inferior (Tr. inf), and Tr. sup + Tr. inf + interlobar artery. The branching patterns of the interlobar artery were subclassified into four subtypes: posterior ascending artery (A. pos), anterior ascending artery (A. ant), A. pos + A. ant, and ascending artery (A. asc). The artery crossing intersegmental planes contains two types: type A, anterior subsegmental artery crossing intersegmental planes (AX1b); type B, recurrent artery crossing intersegmental planes (AX. rec). Conclusion: The variation types of blood vessels in the RUL are complex. This study explored the detailed classification of the interlobar artery and the artery crossing intersegmental planes. It can help thoracic surgeons understand the anatomy variations, accurately locate lesions before surgery, and effectively plan surgeries.

What is the correlation between the defective and splitting posterior segmental bronchus and recurrent artery crossing intersegmental planes in the right upper lobe?

Background: With the prevalence of three-dimensional computed tomography bronchography and angiography (3D-CTBA) and the development of anatomical segmentectomy, studies have confirmed the increased incidence of anomalous veins in patients with tracheobronchial abnormalities. Nevertheless, the characteristic anatomical correlation between bronchus and artery variation remains unknown. Thus, we conducted a retrospective study to investigate recurrent artery crossing intersegmental planes and their associated pulmonary anatomical features by analyzing the incidence and types of the right upper lobe (RUL) bronchus and the artery composition of the posterior segment. Materials and Methods: A total of 600 patients with ground-glass opacity who had undergone 3D-CTBA preoperatively at Hebei General Hospital between September 2020 and September 2022 were included. We reviewed the anatomical variations of the RUL bronchus and artery in these patients using 3D-CTBA images. Results: Among all 600 cases, the defective and splitting B2 contained four types of the RUL bronchial structure: B1 + BX2a, B2b, B3 (11/600, 1.8%); B1, B2a, BX2b + B3 (3/600, 0.5%); B1 + BX2a, B3 + BX2b (18/600, 3%); B1, B2a, B2b, B3 type (29/600, 4.8%). The incidence of recurrent artery crossing intersegmental planes was 12.7% (70/600). The incidence of recurrent artery crossing intersegmental planes with and without the defective and splitting B2 was 26.2% (16/61) and 10.0% (54/539), respectively (p < 0.005). Conclusions: In patients with defective and splitting B2, the incidence of recurrent artery crossing intersegmental planes was increased. Our study provides certain references that surgeons can use to plan and perform RUL segmentectomy.

Electroacupuncture vs Sham Electroacupuncture in the Treatment of Postoperative Ileus After Laparoscopic Surgery for Colorectal Cancer: A Multicenter, Randomized Clinical Trial.

Importance: Despite the adoption of the optimized Enhanced Recovery After Surgery (ERAS) protocol, postoperative ileus (POI) severely impairs recovery after colorectal resection and increases the burden on the health care system. Objective: To assess the efficacy of electroacupuncture (EA) in reducing the duration of POI with the ERAS protocol. Design, Setting, and Participants: This multicenter, randomized, sham-controlled trial was conducted in China from October 12, 2020, through October 17, 2021. There was a 1:1 allocation using the dynamic block random method, and analyses were by intention to treat. Patients 18 years or older undergoing laparoscopic resection of colorectal cancer for the first time were randomly assigned to treatment group by a central system. Interventions: Patients were randomly assigned to 4 sessions of EA or sham electroacupuncture (SA) after surgery. All patients were treated within the ERAS protocol. Main Outcomes and Measures: The primary outcome was the time to first defecation. Secondary outcomes included other patient-reported outcome measures, length of postoperative hospital stay, readmission rate within 30 days, and incidence of postoperative complications and adverse events. Results: A total of 249 patients were randomly assigned to treatment groups. After the exclusion of 1 patient because of a diagnosis of intestinal tuberculosis, 248 patients (mean [SD] age, 60.2 [11.4] years; 153 men [61.7%]) were included in the analyses. The median (IQR) time to first defecation was 76.4 (67.6-96.8) hours in the EA group and 90.0 (73.6-100.3) hours in the SA group (mean difference, -8.76; 95% CI, -15.80 to -1.73; P = .003). In the EA group compared with the SA group, the time to first flatus (median [IQR], 44.3 [37.0-58.2] hours vs 58.9 [48.2-67.4] hours; P < .001) and the tolerability of semiliquid diet (median [IQR], 105.8 [87.0-120.3] hours vs 116.5 [92.0-137.0] hours; P = .01) and solid food (median [IQR], 181.8 [149.5-211.4] hours vs 190.3 [165.0-228.5] hours; P = .01) were significantly decreased. Prolonged POI occurred in 13 of 125 patients (10%) in the EA group vs 25 of 123 patients (20%) in the SA group (risk ratio [RR], 0.51; 95% CI, 0.27-0.95; P = .03). Other secondary outcomes were not different between groups. There were no severe adverse events. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that in patients undergoing laparoscopic surgery for colorectal cancer with the ERAS protocol, EA shortened the duration of POI and decreased the risk for prolonged POI compared with SA. EA may be considered as an adjunct to the ERAS protocol to promote gastrointestinal function recovery and prevent prolonged POI after surgery. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038444.

Superwetting Bi2MoO6/Cu3(PO4)2 Nanosheet-Coated Copper Mesh with Superior Anti-Oil-Fouling and Photo-Fenton-like Catalytic Properties for Effective Oil-in-Water Emulsion Separation.

Superwetting materials with excellent anti-oil-fouling performance for the treatment of oily wastewater are urgently demanded in practice. In this work, aiming at effectively separating diverse oil-in-water emulsions, a multifunctional Bi2MoO6/Cu3(PO4)2 nanosheet-coated copper mesh was successfully fabricated by the combination of chemical oxidation and ultrasonic irradiation deposition methods. The resultant copper mesh exhibited superior superhydrophilicity/underwater superoleophobicity and, more importantly, preferable anti-oil-fouling property benefitting from the stable and firm hydration layer. A series of oil/water separation experiments for the highly emulsified surfactant-free and surfactant-stabilized oil-in-water emulsions were conducted, with the respective permeation fluxes of up to 3000 and 700 L·m-2·h-1 and the corresponding separation efficiencies of 99.5 and 98.6% solely driven by gravity. Meanwhile, considering the photo-Fenton-like catalytic activity of Bi2MoO6, the as-fabricated copper mesh exhibited excellent degradation ability toward organic pollutants under visible light irradiation. More importantly, stability tests were performed to evaluate the ability to cope with the harsh environments for practical applications. With the outstanding performances of high separation efficiency, desirable photo-Fenton-like catalytic capacity, and strong stability, the Bi2MoO6/Cu3(PO4)2 nanosheet-coated copper mesh holds promising potential for purifying emulsified wastewater.

Coordination-Assembled Water-Soluble Anionic Lanthanide Organic Polyhedra for Luminescent Labeling and Magnetic Resonance Imaging.

Lanthanide-containing functional complexes have found a variety of applications in materials science and biomedicine because of their unique electroptical and magnetic properties. However, the poor stability and solubility in water of multicomponent lanthanide organic assemblies significantly limit their practical applications. We report here a series of water-stable anionic Ln2nL3n-type (n = 2, 3, 4, and 5) lanthanide organic polyhedra (LOPs) constructed by deprotonation self-assembly of three fully conjugated ligands (H4L1 and H4L2a/b) featuring a 2,6-pyridine bitetrazolate chelating moiety. The outcomes of the LOPs formation reactions were found to be very sensitive toward the reaction conditions including base, metal source, solvents, and concentrations as characterized by a combination of NMR, high-resolution ESI-MS and X-ray crystallography. Ligands H4L2a/b manifested an excellent sensitization toward lanthanide ions (Ln = EuIII and TbIII), with high luminescent quantum yields for Tb8L2a12 (Φ = 11.2% in water) and Eu8L2b12 (Φ = 76.8% in DMSO) measured in polar solvents. Furthermore, due to the giant molecular weight and rigidity of the polyhedral skeleton, Gd8L2b12 showed a very high longitudinal relaxivity (r1) of 400.53 mM-1S-1. The performance of Gd8L2b12 as potential magnetic resonance imaging contrast agents (CAs) in vivo was evaluated with much longer retention time in the tumor sites compared with the commercial GdIII-based CAs. Dual-modal imaging potential has also been demonstrated with the mixed Eu/Gd LOPs. Our results not only provide a new design route toward water-stable multinuclear lanthanide organic assemblies but also offer potential candidates of supramolecular-edifices for bioimaging and drug delivery.

Mitochondrial EF4 links respiratory dysfunction and cytoplasmic translation in Caenorhabditis elegans.

How animals coordinate cellular bioenergetics in response to stress conditions is an essential question related to aging, obesity and cancer. Elongation factor 4 (EF4/LEPA) is a highly conserved protein that promotes protein synthesis under stress conditions, whereas its function in metazoans remains unknown. Here, we show that, in Caenorhabditis elegans, the mitochondria-localized CeEF4 (referred to as mtEF4) affects mitochondrial functions, especially at low temperature (15°C). At worms' optimum growing temperature (20°C), mtef4 deletion leads to self-brood size reduction, growth delay and mitochondrial dysfunction. Transcriptomic analyses show that mtef4 deletion induces retrograde pathways, including mitochondrial biogenesis and cytoplasmic translation reorganization. At low temperature (15°C), mtef4 deletion reduces mitochondrial translation and disrupts the assembly of respiratory chain supercomplexes containing complex IV. These observations are indicative of the important roles of mtEF4 in mitochondrial functions and adaptation to stressful conditions.