Whole slide image-based weakly supervised deep learning for predicting major pathological response in non-small cell lung cancer following neoadjuvant chemoimmunotherapy: a multicenter, retrospective, cohort study.

Objective: Develop a predictive model utilizing weakly supervised deep learning techniques to accurately forecast major pathological response (MPR) in patients with resectable non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemoimmunotherapy (NICT), by leveraging whole slide images (WSIs). Methods: This retrospective study examined pre-treatment WSIs from 186 patients with non-small cell lung cancer (NSCLC), using a weakly supervised learning framework. We employed advanced deep learning architectures, including DenseNet121, ResNet50, and Inception V3, to analyze WSIs on both micro (patch) and macro (slide) levels. The training process incorporated innovative data augmentation and normalization techniques to bolster the robustness of the models. We evaluated the performance of these models against traditional clinical predictors and integrated them with a novel pathomics signature, which was developed using multi-instance learning algorithms that facilitate feature aggregation from patch-level probability distributions. Results: Univariate and multivariable analyses confirmed histology as a statistically significant prognostic factor for MPR (P-value< 0.05). In patch model evaluations, DenseNet121 led in the validation set with an area under the curve (AUC) of 0.656, surpassing ResNet50 (AUC = 0.626) and Inception V3 (AUC = 0.654), and showed strong generalization in external testing (AUC = 0.611). Further evaluation through visual inspection of patch-level data integration into WSIs revealed XGBoost's superior class differentiation and generalization, achieving the highest AUCs of 0.998 in training and robust scores of 0.818 in validation and 0.805 in testing. Integrating pathomics features with clinical data into a nomogram yielded AUC of 0.819 in validation and 0.820 in testing, enhancing discriminative accuracy. Gradient-weighted Class Activation Mapping (Grad-CAM) and feature aggregation methods notably boosted the model's interpretability and feature modeling. Conclusion: The application of weakly supervised deep learning to WSIs offers a powerful tool for predicting MPR in NSCLC patients treated with NICT.

Efficacy and safety of combining radiotherapy with immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: a real-world study.

BACKGROUND: The significance of local radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC) is well documented. However, the advent of immunotherapy has raised questions regarding the synergistic survival benefits or potential adverse effects. OBJECTIVE: This study aimed to explore whether a combination of RT and systematic immune checkpoint inhibitors (ICIs) can improve the survival outcomes for NSCLC patients. METHODS: Based on collected data patients who received RT were defined as the RT group, and those who had not for any site were defined as the non-RT group. Propensity score matching (PSM) was employed to mitigate bias. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and treatment-related adverse events (AEs). RESULTS: Out of 709 patients (235 in RT group and 474 in non-RT group) were included, with 213 patients per group. The median PFS of the RT group was better than that of the non-RT group (13.8 months versus 9.5 months; p < 0.0001), although no superiority in median overall survival (OS) of the RT group was observed (p = 0.715). However, among the cohort of patients with ≤3 metastases, the median OS of the RT group improved significantly (HR = 0.60, [95% CI 0.44-0.83]; p = 0.004). Treatment-related AEs occurred in 94.5% of RT group patients and in 94.9% of non-RT group patients (p = 0.792), which indicated no observable increase in AEs from RT. CONCLUSIONS: These results demonstrate the tolerability of RT when administered along with immunotherapy, suggesting its potential to positively impact the survival outcomes of NSCLC patients.

Molecular Networking-Guided Discovery of a New Antitumor Pyranonaphthoquinone from Streptomyces tanashiensis DSM 731: Insights from Single-Molecule Stretching Assays.

Guided by molecular networking based on single-molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2-6 were isolated from Streptomyces tanashiensis DSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X-ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC-3, SW620, and C4-2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC50 values below 2.382 µM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single-molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.

Integrating bioinformatics and ferroptosis to reveal the protective mechanism of Astragaloside IV on chronic heart failure rats.

Ferroptosis is an important pathological mechanism of chronic heart failure (CHF). This study aimed to investigate the protective mechanism of Astragaloside IV (AS-IV) on CHF rats by integrating bioinformatics and ferroptosis. CHF-related targets and ferroptosis-related targets were collected. After the intersection, the common targets were obtained. The PPI network of the common targets was constructed, and topological analysis of the network was carried out. The target with the highest topological parameter values was selected as the key target. The key target p53 was obtained through bioinformatics analysis, and its molecular docking model with AS-IV was obtained, as well as molecular dynamics simulation analysis. The rat models of CHF after myocardial infarction were established by ligation of left coronary artery and treated with AS-IV for 4 weeks. AS-IV treatment significantly improved cardiac function in CHF rats, improved cardiomyocyte morphology and myocardial fibrosis, reduced mitochondrial damage, decreased myocardial MDA and Fe2+ content, increased GSH content, inhibited the expression of p53 and p-p53, and up-regulated the expression of SLC7A11 and GPX4. In conclusion, AS-IV improved cardiac function in CHF rats, presumably by regulating p53/SLC7A11/GPX4 signaling pathway and inhibiting myocardial ferroptosis.

Chloride-Ion-Enriched Solid Electrolyte Interphase with Rapid Na+ Migration toward High-Performance Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have emerged as potential alternatives to lithium-ion batteries (LIBs), particularly for large-scale applications. Alloy-type anode materials for sodium-ion batteries are esteemed as prospective candidate materials for sodium-ion anodes, owing to their elevated theoretical capacity, heightened utilization efficiency, and minimal production of insulating byproducts. However, the severe volume changes and sluggish ion diffusion kinetics can lead to irreversible particle fragmentation and reaggregation phenomena, ultimately resulting in electrode degradation. Additionally, repetitive volume changes can cause an unstable solid electrolyte interphase (SEI). This study presents the synthesis of chloride-ion-modulated bimetallic SnSb/C nanoparticle anode materials, highlighting the following advantages: (i) Designing a bimetallic SnSb alloy structure serves to buffer the structural stresses generated during sodium insertion/extraction processes, effectively mitigating particle fracture phenomena induced by electrode material expansion/contraction. (ii) Nanostructuring both alloy materials enables the full utilization of active materials and shortens diffusion pathways, thereby significantly enhancing the diffusion rate of sodium ions. (iii) Introducing a carbonaceous matrix serves to alleviate self-agglomeration phenomena of the material during charge/discharge cycles, enhancing the material's conductivity and structural stability. (iv) Utilizing chloride-ion interface modification to achieve a chloride-rich solid-electrolyte interphase (SEI) enhances battery performance.

Genome-Driven Discovery of Antiviral Atralabdans A-C from the Soil-Dwelling Streptomyces atratus.

Heterologous expression of an atr terpenoid gene cluster derived from Streptomyces atratus Gö66 in S. albus J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (1-3), along with a known compound, labdanmycin A. Compounds 1-3 were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed. Compounds 1-3 exhibited inhibitory activity against the human neurotropic coxsackievirus B3 (CVB3); 1 was the most potent, surpassing the positive control ribavirin with a higher therapeutic index.

Accelerated and Guided Zn2+ Diffusion via Polarized Interface Engineering Toward High Performance Wearable Zinc-Ion Batteries.

Rechargeable aqueous Zn-ion batteries (ZIBs) are considered as a new energy storage device for wearable electronic equipment. Nowadays, dendrite growth and uneven deposition of zinc have been the principal problems to suppress the development of high-performance wearable zinc-ion batteries. Herein, a perovskite material of LaAlO3 nanoparticle has been applied for interface engineering and zinc anode protection. By adjusting transport channels and accelerating the Zn2+ diffusion, the hydrogen evolution reaction potential is improved, and electric field distribution on the Zn electrode surface is regulated to navigate the fast and uniform deposition of Zn2+. As a proof of demonstration, the assembled LAO@Zn||MnO2 batteries can display the highest capacity of up to 140 mAh g-1 without noticeable decay even after 1000 cycles. Moreover, a motor-driven fan and electronic wristwatch powered by wearable ZIBs can demonstrate the practical feasibility of LAO@Zn||MnO2 in wearable electronic equipment.

Prospects for the Protective Mechanisms and Compounds of Bufei Huoxue Capsule against COVID-19 Convalescence: Evaluation of Integrating UHPLC-HRMS Analysis and Network Pharmacology Strategy.

INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

The preservation of cervical flexibility helps maintain cervical sagittal alignment after laminoplasty.

BACKGROUND CONTEXT: Cervical spine range of motion (ROM) is a critical factor in changes in cervical sagittal alignment (CSA) and clinical outcomes after cervical laminoplasty (LMP). However, the impact of postoperative cervical ROM on CSA after cervical LMP is still unclear. PURPOSE: Evaluating the imaging and symptomatic data from patients with cervical spondylotic myelopathy (CSM) to identify the influence of postoperative cervical ROM on post-LMP CSA and surgical outcomes. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Eighty-six patients undergoing LMP due to multilevel CSM OUTCOME MEASURES: Radiographic parameters were measured before surgery and at follow-up: cervical lordosis (CL), T1 slope (T1S), cervical sagittal vertical axis (cSVA), CL in flexion (Flex CL), CL in extension (Ext CL), total cervical spine range of motion (ROM), cervical spine range of flexion (Flex ROM), and cervical spine range of extension (Ext ROM). Japanese Orthopedic Association (JOA) and visual analog score (VAS) were used to assessed clinical outcomes. Other parameters included age, gender, body mass index (BMI), follow-up time, number of surgical segments, proximal level, distalis level, and collar wear time. METHODS: We divided patients according to the changes in CSA (loss of cervical lordosis (LCL)>10°, or ≤10°; an increase in cervical sagittal vertical axis (I-cSVA) >10mm, or ≤10mm). A receiver-operating characteristic curve (ROC) analysis was constructed to identify the optimal cut-off value to discriminate the patients with and without postoperative deterioration of CSA. RESULTS: The postoperative total and Flex ROM were significantly lower in the LCL>10° and I-cSVA>10mm groups. Multivariate logistic regression analysis showed that low post-Flex ROM was significant risk factor for postoperative deterioration of CSA. ROC showed that the cut-off value for postoperative Flex ROM was 15.60°. Improvements in JOA recovery rate and neck pain were more significant in the flexibility group (post-Flex ROM ≥15.6°) after surgery. Patients in the stiffness group (post-Flex ROM <15.6°) wore a collar longer. CONCLUSIONS: The preservation of cervical flexibility can maintain CSA after cervical LMP. Postoperative cervical stiffness is related to poor surgical outcomes because significant cervical kyphotic change and sagittal imbalance are likely to occur after surgery. Prolonged wearing of cervical collar is correlated with cervical stiffness following cervical LMP.

Network and Experimental Pharmacology on Mechanism of Yixintai Regulates the TMAO/PKC/NF-κB Signaling Pathway in Treating Heart Failure.

Objective: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation. Materials and Methods: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database. A rat heart failure model was established by ligating the anterior descending branch of the left coronary artery. A small animal color Doppler ultrasound imaging system detected cardiac function indicators. Hematoxylin-eosin (HE), Masson's, and electron microscopy were used to observe the pathological morphology of the myocardium in rats with heart failure. The network pharmacology analysis results were validated by ELISA, qPCR, and Western blotting. Results: A total of 107 effective targets were obtained by combining compound targets and eliminating duplicate values. PPI analysis showed that inflammation-related proteins (TNF and IL1B) were key targets for treating heart failure, and KEGG enrichment suggested that NF-κB signaling pathway was a key pathway for YXT treatment of heart failure. Animal model validation results indicated the following: YXT can significantly reduce the content of intestinal microbiota metabolites such as trimethylamine oxide (TMAO) and improve heart failure by improving the EF and FS values of heart ultrasound in rats and reducing the levels of serum NT-proBNP, ANP, and BNP to improve heart failure. Together, YXT can inhibit cardiac muscle hypertrophy and fibrosis in rats and improve myocardial ultrastructure and serum IL-1ß, IL-6, and TNF-α levels. These effects are achieved by inhibiting the expressions of NF-κB and PKC. Conclusion: YXT regulates the TMAO/PKC/NF-κB signaling pathway in heart failure.

Fluorine-ion-regulated yolk-shell carbon-silicon anode material for high performance lithium ion batteries.

Silicon is considered as the next-generation anode material for lithium-ion batteries due to its high theoretical specific capacity and abundant crustal abundance. However, its poor electrical conductivity results in slow diffusion of lithium ions during battery operation. Simultaneously, the alloying process of silicon undergoes a 300 % volume change, leading to structural fractures in silicon during the cycling process. As a result, it loses contact with the current collector, continuously exposing active sites, and forming a sustained solid electrolyte interface (SEI) membrane. This paper presents the design of a fluorine-ion-regulated yolk-shell carbon-silicon anode material, highlighting the following advantages: (a) Alleviating volume changes through the design of a yolk-shell structure, thereby maintaining material structural integrity during cycling. (b) Carbon shell prevents silicon from coming into contact with the electrolyte, simultaneously improving silicon's electrical conductivity and increasing ion/electron conductivity. (c) Utilizing fluorine-ion interface modification to obtain an SEI membrane rich in fluorine components (such as LiF), thereby enhancing its long cycling performance. The F-Si@Void@C exhibits outstanding electrochemical performance, with a reversible capacity of 1166 mAh/g after 900 cycles at a current density of 0.5 A/g.

How does cervical sagittal profile change after the spontaneous compensation of global sagittal imbalance following one- or two-level lumbar fusion.

PURPOSE: This study aimed to evaluate the cervical sagittal profile after the spontaneous compensation of global sagittal imbalance and analyze the associations between the changes in cervical sagittal alignment and spinopelvic parameters. METHODS: In this retrospective radiographic study, we analyzed 90 patients with degenerative lumbar stenosis (DLS) and sagittal imbalance who underwent short lumbar fusion (imbalance group). We used 60 patients with DLS and sagittal balance as the control group (balance group). Patients in the imbalance group were also divided into two groups according to the preoperative PI: low PI group (≤ 50°), high PI group (PI > 50°). We measured the spinal sagittal alignment parameters on the long-cassette standing lateral radiographs of the whole spine. We compared the changes of spinal sagittal parameters between pre-operation and post-operation. We observed the relationships between the changes in cervical profile and spinopelvic parameters. RESULTS: Sagittal vertical axis (SVA) occurred spontaneous compensation (p = 0.000) and significant changes were observed in cervical lordosis (CL) (p = 0.000) and cervical sagittal vertical axis (cSVA) (p = 0.023) after surgery in the imbalance group. However, there were no significant differences in the radiographic parameters from pre-operation to post-operation in the balance group. The variations in CL were correlated with the variations in SVA (R = 0.307, p = 0.041). The variations in cSVA were correlated with the variations in SVA (R=-0.470, p = 0.001). CONCLUSION: Cervical sagittal profile would have compensatory changes after short lumbar fusion. The spontaneous decrease in CL would occur in patients with DLS after the spontaneous compensation of global sagittal imbalance following one- or two-level lumbar fusion. The changes of cervical sagittal profile were related to the extent of the spontaneous compensation of SVA.

Change of cervical flexion range of motion influences postoperative sagittal alignment of the cervical spine after laminoplasty.

OBJECTIVE: The relationships between preoperative cervical spine range of motion (ROM) and postoperative cervical sagittal alignment (CSA), and clinical outcomes after laminoplasty (LMP) have been widely studied. However, the impact of ROM changes on postoperative CSA and clinical outcomes after LMP remains unclear. Herein, patients with cervical spondylotic myelopathy (CSM) were retrospectively analyzed to explore the association between postoperative cervical ROM changes and CSA and surgical outcomes. METHODS: Patients who underwent cervical LMP at our hospital between January 2019 to June 2022 were retrospectively reviewed. CSA parameters were measured before the surgery and at the final follow-up. Loss of cervical lordosis (LCL) was defined as preoperative cervical lordosis (CL) - postoperative CL. An increase in the cervical sagittal vertical axis (I-cSVA) was defined as postoperative cervical sagittal vertical axis (cSVA) - preoperative cSVA. We defined the changes in cervical flexion range of motion (△Flex ROM, preoperative Flex ROM minus postoperative Flex ROM) > 10° as L- Flex ROM group, and △Flex ROM ≤ 10° as S- Flex ROM group. Japanese Orthopedic Association (JOA) score and visual analog score (VAS) were used to assess the surgical outcomes. RESULTS: The study comprised 74 patients and the average follow-up period was 31.83 months. CL, total ROM, and Flex ROM decreased and cSVA increased after cervical LMP. LCL and I-cSVA were positively correlated with △Flex. Multiple linear regression analysis showed that a decrease in the Flex ROM was a risk factor for LCL and I-cSVA after LMP. LCL and I-cSVA were higher in the L-Flex ROM group than in the S-Flex ROM group. Postoperative JOA and the JOA recovery rate were worse in the L-Flex ROM group than in the S-Flex ROM group. CONCLUSIONS: Cervical total and Flex ROM decreased after cervical LMP. The reduction of Flex ROM was associated with LCL and I-cSVA after surgery. The preservation of cervical Flex ROM helps maintain CSA after LMP. Therefore, more attention should be paid to maintaining cervical ROM to obtain good CSA and surgical effects after cervical LMP.

Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Accurate location describe and management of lymph node recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Describe the accurate locations of lymph node recurrence (LNR) of Chinese patients with postoperative thoracic esophageal squamous cell carcinoma (ESCC) is essential for determining the need for further surveillance protocols and treatments. The authors aimed to evaluate the patterns of postoperative ESCC and its current risk stratification with LNR. METHODS: This population-based cohort study included a retrospective review of the medical records and image material of patients with ESCC who underwent LNR after radical surgery between January 2013 and September 2022, with a median follow-up time of 5.71 years. Clinical features were extracted from these records, and survival analysis was performed. The primary endpoint was the accurate location and range of LNR according to the nomenclature of the Japanese Society for Esophageal Diseases. The second endpoints was to explore the related factors of recurrence range and overall survival. RESULTS: A total of 3268 lymph node regions were recurrence from 1129 patients, with a mean of 2.89 regions per patient. No.104, 106, and 107 was the most common recurrence of thoracic ESCC with an LNR rate higher than 15%. In upper thoracic ESCC, No.105 was a common recurrence site and abdominal LNR was rare. In lower thoracic ESCC, retroperitoneal lymph node was a unique regions (15.4%). Anastomotic recurrence is an important recurrence pattern in patients with postoperative esophageal cancer, with an incidence of 24.5%. Rates of LNR in range of lymph node dissection was low (13.9%). The median time of LRT was 20.0 (1.5-184.0) months. High range of recurrence was associated with significantly poorer OS in patients. Multiple linear regression analysis identified demonstrated N stage, tumor differentiation, adjuvant radiotherapy, and total lymph nodes removed were association with recurrence range for patients. CONCLUSIONS: Supraclavicular and upper mediastinums lymph nodes were common recurrence site for ESCC patients, and careful initial staging and surveillance are needed. Thorough lymph node dissection may reduce the range of regional recurrence.

Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments.

Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.

The application of three-dimensional custom-made prostheses in chest wall reconstruction after oncologic sternal resection.

BACKGROUND AND OBJECTIVES: As one of the cutting-edge advances in the field of reconstruction, three-dimensional (3D) printing technology has been constantly being attempted to assist in the reconstruction of complicated large chest wall defects. However, there is little literature assessing the treatment outcomes of 3D printed prostheses for chest wall reconstruction. This study aimed to analyze the surgical outcomes of 3D custom-made prostheses for the reconstruction of oncologic sternal defects and to share our experience in the surgical management of these rare and complex cases. METHODS: We summarized the clinical features of the sternal tumor in our center, described the surgical techniques of the application of 3D customized prosthesis for chest wall reconstruction, and analyzed the perioperative characteristics, complications, overall survival (OS), and recurrence-free survival of patients. RESULTS: Thirty-two patients with the sternal tumor who underwent chest wall resection were identified, among which 13 patients used 3D custom-made titanium implants and 13 patients used titanium mesh for sternal reconstruction. 22 cases were malignant, and chondrosarcoma is the most common type. The mean age was 46.9 years, and 53% (17/32) of the patients were male. The average size of tumor was 6.4 cm, and the mean defect area was 76.4 cm2. 97% (31/32) patients received R0 resection. Complications were observed in 29% (9/32) of patients, of which wound infection (22%, 7/32) was the most common. The OS of the patients was 72% at 5 years. CONCLUSION: We demonstrated that with careful preoperative assessment, 3D customized prostheses could be a viable alternative for complex sternal reconstruction.

Analysis of Mechanical Characteristics of the Swing Angle Milling Head of a Heavy Computer Numerical Control Milling Machine and Research on the Light Weight of a Gimbal.

As the key component of a five-axis CNC planer-type milling machine, the integral mechanical property of the A/C swing angle milling head directly affects the machining accuracy and stability of the milling machine. Taking the mechanical A/C swing-angle milling head of a five-axis numerical-control gantry milling machine as the research object, the stress deformation characteristics and natural frequency of the swing-angle milling head under actual working conditions were studied using finite-element analysis. Based on the analytical results, it was determined that the cardan frame, with its large mass proportion and strong rigidity of the whole milling head, is the object to be optimized. The topological optimization of the cardan frame, in which achieving the minimum flexibility was the optimization objective, was carried out to determine the quality reduction area. By comparing the simulation results of the cardan frames of three different rib plate structures, it was shown that the cardan frame performance of the ten-type rib plate structure was optimal. The analytical results showed that, when the cardan frame met the design requirements for stiffness and strength, the mass after optimization was reduced by 13.67% compared with the mass before optimization, the first-order natural frequency was increased by 7.9%, and the maximum response amplitude was reduced in all directions to avoid resonance, which was beneficial to the improvement of the dynamic characteristics of the whole machine. At the same time, the rationality and effectiveness of the lightweight design method of the cardan frame were verified, which has strong engineering practicality. The research results provide an important theoretical basis for the optimization of other machine tool gimbals and have important practical significance and application value.

Mitophagy plays a "double-edged sword" role in the radiosensitivity of cancer cells.

Mitochondria are organelles with double-membrane structure of inner and outer membrane, which provides main energy support for cell growth and metabolism. Reactive oxygen species (ROS) mainly comes from mitochondrial and can cause irreversible damage to cells under oxidative stress. Thus, mitochondrial homeostasis is the basis for maintaining the normal physiological function of cells and mitophagy plays a pivotal role in the maintenance of mitochondrial homeostasis. At present, to enhance the sensitivity of cancer cells to radiotherapy and chemotherapy by regulating mitochondria has increasingly become a hot spot of cancer therapy. It is particularly important to study the effect of ionizing radiation (IR) on mitochondria and the role of mitophagy in the radiosensitivity of cancer cells. Most of the existing reviews have focused on mitophagy-related molecules or pathways and the impact of mitophagy on diseases. In this review, we mainly focus on discussing the relationship between mitophagy and radiosensitivity of cancer cells around mitochondria and IR.