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Background: Low-dose Computed Tomography (CT) is used for the detection of pulmonary nodules, but the ambiguous risk evaluation causes overdiagnosis. Here, we explored the significance of the DNA methylation of 7 genes including TAC1, CDO1, HOXA9, ZFP42, SOX17, RASSF1A and SHOX2 in the blood cfDNA samples in distinguishing lung cancer from benign nodules and healthy individuals. Method: A total of 149 lung cancer patients [72 mass and 77 ground-glass nodules (GGNs)], 5 benign and 48 healthy individuals were tested and analyzed in this study. The lasso-logistic regression model was built for distinguishing cancer and control/healthy individuals or IA lung cancer and non-IA lung cancer cases. Results: The positive rates of methylation of 7 genes were higher in the cancer group as compared with the healthy group. We constructed a model using age, sex and the ΔCt value of 7 gene methylation to distinguish lung cancer from benign and healthy individuals. The sensitivity, specificity and AUC (area under the curve) were 86.7%, 81.4% and 0.891, respectively. Also, we assessed the significance of 7 gene methylation together with patients’ age and sex in distinguishing of GGNs type from the mass type. The sensitivity, specificity and AUC were 77.1%, 65.8% and 0.753, respectively. Furthermore, the methylation positive rates of CDO1 and SHOX2 were different between I-IV stages of lung cancer. Specifically, the positive rate of CDO1 methylation was higher in the non-IA group as compared with the IA group. Conclusion: Collectively, this study reveals that the methylation of 7 genes has a big significance in the diagnosis of lung cancer with high sensitivity and specificity. Also, the 7 genes present with certain significance in distinguishing the GGN type lung cancer, as well as different stages. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have shown a powerful benefit in the neoadjuvant therapy for esophageal cancer, but evidence for its safety and efficacy is limited and may not reflect real-world practice. We retrospectively reviewed the database of treatment-naive patients from 15 esophageal cancer centers in China who received ICIs as neoadjuvant treatment for locally advanced esophageal cancer from May 2019 to December 2020. The primary endpoints were rate and severity of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs). Secondary endpoints included pathologically complete response (pCR) rate, R0 resection rate, mortality and morbidity. Among the 370 patients, 311 (84.1%) were male with a median age of 63 (range: 30–81) years and stage III or IVa disease accounted for 84.1% of these patients. A total of 299 (80.8%) patients were treated with ICIs and chemotherapy. TRAEs were observed in 199 (53.8%) patients with low severity (grade 1-2, 39.2%; grade 3-4, 13.2%; grade 5, 1.4%), and irAEs occurred in 24.3% of patients and were mostly of grade 1-2 severity (21.1%). A total of 341 (92.2%) patients had received surgery and R0 resection was achieved in 333 (97.7%) patients. The local pCR rate in primary tumor was 34.6%, including 25.8% of ypT0N0 and 8.8% of ypT0N+. The rate of postoperative complications was 41.4% and grade 3 or higher complications occurred in 35 (10.3%) patients. No death was observed within 30 days after surgery, and three patients (0.9%) died within 90 days postoperatively. This study shows acceptable toxicity of neoadjuvant immunotherapy for locally advanced esophageal cancer in real-world data. Long-term survival results are pending for further investigations. [ABSTRACT FROM AUTHOR]

• A morphing nose cone that can achieve length and bending angle adjustments is introduced into an underwater glider. • The optimal configurations of morphing nose cone are determined by multi-objective optimization and surrogate models. • A novel design scheme for the driving mechanism of the morphing nose cone and its principle prototype. • The morphing nose cone effectively balances the glider energy utilization rate, static stability, and voyage velocity. As an autonomous underwater vehicle with low energy consumption, underwater glider has been widely applied to long-term ocean exploration missions. To better deal with complex working environments and various mission requirements, morphing underwater gliders are receiving increasing attention. This paper attempts to introduce the morphing nose cone that can achieve length and bending angle adjustments into the glider to improve its comprehensive performance. The performance indicators of the glider include energy utilization rate, static stability, and voyage velocity. Based on dynamic analysis and CFD simulation, performance evaluation models of a glider are established, and the effect of morphing nose cone configurations on the glider's hydrodynamic characteristics is discussed. Then, mathematical optimization models for morphing parameters of the nose cone are established, and they are solved by a multi-objective optimization algorithm and surrogate model technology. Especially, the diving and ascending motion processes of the glider are separately considered in the above optimization. Finally, the multi-objective optimization results are used for guiding the driving mechanism design of the morphing nose cone, and the principle prototype of a novel design scheme is manufactured to verify the feasibility. The research methods and results will provide new development direction for the morphing underwater glider technology. [ABSTRACT FROM AUTHOR]

Background: It is known that ypN0 status after induction treatment can be divided into "natural" N0 (cN0/ypN0) and "downstaged" N0 (cN+/ypN0). Whether natural N0 patients and downstaged N0 patients with esophageal squamous cell carcinoma (ESCC) after neoadjvant chemoradiotherapy (nCRT) have similar prognosis is unknown.Methods: An institutional database was reviewed to identify ESCC patients after nCRT, whose CT scans were retrieved and reviewed to reclassify nodal status. The patients were divided into 3 groups based on node status: natural N0, downstaged N0, and ypN+. Impact of nodal status on survival and associations with survival were analyzed.Results: We identified 110 patients, and 25 had natural N0 disease, 52 had downstaged N0 disease, and 33 had ypN+ disease. The 3-year OS was 76.7%, 79.5%, and 49% in natural N0, downstaged N0 and ypN+ group, respectively, and, correspondingly, the 3-year DFS was 77%, 73.9%, and 36.3%. In multivariable analysis, OS (P = 0.794) and DFS (P = 0.957) did not differ between natural N0 and downstaged N0 groups, but it was significantly shorter in ypN+ group (OS, P = 0.032; DFS, P = 0.021). In subgroups with "poor response" of primary tumor, the prognosis of natural N0 and downstaged N0 paitents was poor almost identical to ypN+ in both OS (P = 0.721; P = 0.252) and DFS (P = 0.694; P = 0.114).Conclusions: The ypN0 status is an important hallmark demonstrating the effectiveness of nCRT for ESCC, regardless of cN status. Additionally, the survival of natural N0 and downstaged N0 patients with bad response at primary site may be poor, similar to ypN+ patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the short-term health-related quality of life (HRQL) between the two different routes of gastric tube reconstruction after minimally invasive esophagectomy (MIE).Methods: From January 2007 to June 2009, 97 patients who underwent three-incision subtotal MIE were enrolled in this retrospective study. Among them, 49 patients followed prevertebral route and 48 patients followed retrosternal route. The questionnaires (EORTC QLQ C-30 and OES-18) were applied to assess the HRQL of the patients before and 2, 4, 12, 24 weeks after operation.Results: All the patients underwent operation with no mortality. No statistical difference was found in age, gender, serum albumin level, the level of growth in the esophagus, pathological diagnosis, tumor stage, operation time, blood loss or ICU stay between the two groups. The perioperative complication rate was 35.4% in retrosternal group and 32.7% in prevertebral group (P = 0.774). However, the rate of cervical anastomotic leak in the retrosternal group was much higher (20.8 vs. 6.1%, P = 0.033). But the rate of cardiac or pulmonary complication in the retrosternal group seemed to be lower (10.4 vs. 22.4%, P = 0.110). Besides, the rate of anastomotic stricture was similar (6.3 vs. 10.2%, P = 0.735). And all HRQL measures did not show major differences between the two groups before operation. However, at the time of 2 weeks after operation, the dysphagia and eating problem questionnaires scores were higher in retrosternal group than in prevertebral group, which meant that the patients in retrosternal group suffered more severe problems; meanwhile, the scores of global quality scale in retrosternal group was also lower, which indicated that the patients had a worse global quality of life. Whereas, at the time of 12 and 24 weeks after operation, the dyspnoea and reflux symptom questionnaire scores were lower in retrosternal group than in prevertebral group, which revealed that there were less problems in the patients of retrosternal group; meanwhile, the score of global quality scale in retrosternal group was higher conversely, which suggested that the patients gain a better status in global quality of life.Conclusion: Our results suggest that retrosternal route may be a good alternative choice for MIE in view of better HRQL after operation, although it has higher risk of anastomotic leak that might lead to worse HRQL in early period. [ABSTRACT FROM AUTHOR]

Clonal haematopoiesis (CH) is an age-associated clonal expansion of blood cells driven by leukaemia-associated somatic mutations. Although CH has been reported to be a risk factor for leukaemia and a number of non-haematopoietic diseases, its role in perioperative medicine remains unexplored. This was a single-centre, prospective, observational study. Patients undergoing radical oesophagectomy were enrolled, and peripheral blood samples were collected for DNA sequencing. Patients with haematopoietic somatic mutations (variant allele frequencies ≥1%) in the DNMT3A gene, TET2 gene, or both were defined as CH carriers. The primary outcome was the incidence of severe postoperative complications (Clavien–Dindo classification ≥3). The secondary outcomes included the major types of postoperative complications, mortality, and other common perioperative variables. Clonal haematopoiesis was found in 21.2% (33/156) of the patients (mean age: 66 yr [range: 26–79 yr]; 83% males). Some 14/33 (42.4%) patients with CH had severe postoperative complications, compared with patients without CH carriers (28 / 123 [22.8%]; P =0.024). Multivariable logistic regression analysis showed that CH was associated with an increased risk of developing severe postoperative complications (odds ratio, 3.63; 95% confidence interval, 1.37–9.66; P =0.010). Among the major postoperative complications, the incidence of pulmonary complications was significantly higher in the patients with CH than in those without CH (15 in 33 [45.5%] vs 30 in 123 [24.4%], P =0.018). Clonal haematopoiesis was associated with a higher incidence of severe postoperative complications in patients undergoing radical oesophagectomy, suggesting that clonal haematopoiesis can play an important role in perioperative medicine. ChiCTR2100044175 (Chinese Clinical Trial Registry, http://www.chictr.org.cn/showproj.aspx?proj=123193). [ABSTRACT FROM AUTHOR]

Background Esophageal squamous cell carcinoma (ESCC) tends to metastasize in a multidirectional fashion through the extensive submucosal lymphatics, even in early stage. Subcarinal lymph nodes (LNs) is regarded as one of regional lymph node stations for esophageal cancer and suggested to be dissected by Guildlines. However, the metastatic rate of subcarinal LNs is relatively low and dissection reportedly may increase pulmonary complications. The purpose of this study was to investigate the impact of subcarinal LN dissection on short-term and long-term outcomes in patients with superficial ESCC and aimed at illustrating the value of subcarinal LN dissection in superficial ESCC. Methods From January 2010 to December 2015, 490 patients with pT1 ESCC were enrolled in the study. Patients in subcarinal dissection (Group 1) or non-dissection group (Group 2) were matched randomly in a 2:1 ratio, eventually, 255 patients were selected for further statistical analysis. Results The metastasis rate of subcarinal LNs in superficial ESCC was 1.24% and significantly lower than perigastric, paraesophageal or bilateral recurrent laryngeal nerves station (7.14–9.96%). Compared with Group 1, Group 2 had shorter operation time (193 ± 35 vs. 204 ± 39, P  = 0.016), less blood loss (157 ± 48 vs. 178 ± 29, P  = 0.011), less harvested LNs (20.7 ± 8.8 vs. 24.5 ± 9.5, P  = 0.002) as well as lower incidence of pulmonary complications (9.4 vs. 20%, P  = 0.032). At a median follow-up of 46 months, the recurrent rates in two groups were similar (16.5 vs. 15.3%, P  = 0.809). The 3-year overall survival(OS) rate of Group 1 and 2 was 89.7% and 90.4%, correspondingly, the 3-year disease-free survival (DFS) was 83.5% and 88.5%, respectively. Survival analysis revealed no OS (P  = 0.992) and DFS (P  = 0.665) reductions in Group 2. Subgroup analyses stratified by pT and pN status also confirmed no significant differences in OS and DFS. In univariate and multivariate analyses, subcarinal LN dissection was not a predictive factor of prognosis in superficial ESCC. View large Download slide View large Download slide Conclusion The present study was the first available analysis investigating values of subcarinal LN dissection in superficial ESCC. Our results showed subcarinal LN dissection did not contribute to improved survival, whereas may increase the risk of postoperative pulmonary complications in superficial ESCC. Therefore, subcarinal LN dissection could be omitted for patients with superficial ESCC. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Key Points: Question: Will an immune checkpoint blocker in combination with perioperative chemotherapy improve event-free survival and major pathological response in patients with resectable non–small cell lung cancer (NSCLC)? Findings: The prespecified interim analysis of event-free survival revealed that the addition of toripalimab to platinum-based chemotherapy showed statistically significant and clinically meaningful improvement in event-free survival compared with chemotherapy alone in patients with stage III NSCLC, while maintaining a manageable safety profile. Meaning: The demonstrated event-free survival benefits support the use of toripalimab in combination with platinum-based chemotherapy as a new treatment option for patients with stage III resectable NSCLC. Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non–small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P <.001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P <.001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440 This randomized clinical trial compares the effects of toripalimab in combination with platinum-based chemotherapy vs chemotherapy alone on event-free survival and major pathological response in patients with stage III resectable non–small cell lung cancer. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is one of the common manifestations of end‐stage lung disease. Chronic lung failure after lung transplantation is mainly caused by bronchiolitis obliterans syndrome (BOS) and is mainly characterized by lung tissue fibrosis. Pulmonary epithelial‐mesenchymal transformation (EMT) is crucial for pulmonary fibrosis. Telocytes (TCs), a new type of mesenchymal cells, play a protective role in various acute injuries. For exploring the anti‐pulmonary fibrosis effect of TCs in the BOS model in vitro and the related mechanism, rat tracheal epithelial (RTE) cells were treated with transforming growth factor‐β (TGF‐β) to simulate lung tissue fibrosis in vitro. The RTE cells were then co‐cultured with TCs primarily extracted from rat lung tissue. Western blot, Seahorse XF Analysers and enzyme‐linked immunosorbent assay were used to detect the level of EMT and aerobic respiration of RTE cells. Furthermore, anti‐hepatocyte growth factor (anti‐HGF) antibody was exogenously added to the cultured cells to explore further mechanisms. Moreover, hexokinase 2 (HK2) in RTE cells was knocked down to assess whether it influences the blocking effect of the anti‐HGF antibody. TGF‐β could induce lung tissue fibrosis in RTE cells in vitro. Nevertheless, TCs co‐culture decreased the level of EMT, glucose metabolic indicators (lactate and ATP) and oxygen levels. Furthermore, TCs released hepatocyte growth factor (HGF). Therefore, the exogenous addition of anti‐HGF antibody in the co‐culture system blocked the anti‐lung tissue fibrosis effect. However, HK2 knockdown attenuated the blocking effect of the anti‐HGF antibody. In conclusion, TCs can protect against lung tissue fibrosis by releasing HGF, a process dependent on HK2. [ABSTRACT FROM AUTHOR]

Esophageal carcinoma is among the most fatal malignancies with increasing incidence globally. Tumor onset and progression can be driven by metabolic reprogramming, especially during esophageal carcinoma development. Exosomes, a subset of extracellular vesicles, display an average size of ∼100 nanometers, containing multifarious components (nucleic acids, proteins, lipids, etc.). An increasing number of studies have shown that exosomes are capable of transferring molecules with biological functions into recipient cells, which play crucial roles in esophageal carcinoma progression and tumor microenvironment that is a highly heterogeneous ecosystem through rewriting the metabolic processes in tumor cells and environmental stromal cells. The review introduces the reprogramming of glucose, lipid, amino acid, mitochondrial metabolism in esophageal carcinoma, and summarize current pharmaceutical agents targeting such aberrant metabolism rewiring. We also comprehensively overview the biogenesis and release of exosomes, and recent advances of exosomal cargoes and functions in esophageal carcinoma and their promising clinical application. Moreover, we discuss how exosomes trigger tumor growth, metastasis, drug resistance, and immunosuppression as well as tumor microenvironment remodeling through focusing on their capacity to transfer materials between cells or between cells and tissues and modulate metabolic reprogramming, thus providing a theoretical reference for the design potential pharmaceutical agents targeting these mechanisms. Altogether, our review attempts to fully understand the significance of exosome-based metabolic rewriting in esophageal carcinoma progression and remodeling of the tumor microenvironment, bringing novel insights into the prevention and treatment of esophageal carcinoma in the future. [Display omitted] • Overview of metabolic reprogramming in esophageal carcinoma. • Functions and potential clinical application of exosomes in esophageal carcinoma. • Exosomes-mediated metabolic reprogramming in esophageal carcinoma progression. • Exosome-mediated metabolic reprogramming in the tumor microenvironment remodeling. [ABSTRACT FROM AUTHOR]

Biomarker-driven neoadjuvant treatment regimens may be explored based on multi-omics exploratory analysis in the early-phase studies when longitudinal peripheral blood and tumour specimens are available. Keywords: biomarkers; locally advanced oesophagal squamous cell carcinoma; neoadjuvant immunotherapy EN biomarkers locally advanced oesophagal squamous cell carcinoma neoadjuvant immunotherapy 1 4 4 10/03/23 20230901 NES 230901 MAIN TEXT The emergence of immune checkpoint agents has transformed neoadjuvant therapy into a life-saving treatment with curative promise. The NATION-1907 trial has identified "Interferon/Epithelial-mesenchymal transition (IFN/EMT) score" signature and immune-enriched tumour microenvironment phenotype to stratify for well responders who would benefit from neoadjuvant adebrelimab blockade, highlighting that anti-PD-L1 monotherapy may be sufficient in the immune "inflamed" patients. [Extracted from the article]

Recently, solid-state amorphization through temperature-induced martensitic transition has been reported. The stability of the amorphous martensite phase, which co-exists with a crystalline counterpart, is intriguing but remains unclear. In this work, we studied the structural stability of a Ti59.1Zr37Cu2.3Fe1.6 amorphous martensite alloy by combining in situ high-pressure synchrotron x-ray diffraction with ex situ transmission electron microscopy. During compression at room temperature, an irreversible pressure-induced crystallization of the amorphous martensite phase into a β-Ti phase is revealed. Qualitative analysis reveals the important role of the local atomic strain in stabilizing/destabilizing amorphous martensite alloys and its high tunability of the local atomic strain under high pressure. [ABSTRACT FROM AUTHOR]

Introduction. LAMA1, also known as laminin subunit α1, is a member of the laminin family, which is widely reported to be a key basement membrane molecule that affects various biological activities and is associated with many kinds of diseases. We aimed to investigate the association between LAMA1single-nucleotide polymorphisms and the occurrence and progression of esophageal squamous cell carcinoma in the Chinese population. Method. 2,186 participants were collected retrospectively between October 2008 and January 2017, including 1,043 ESCC patients and 1,143 noncancer patients. A 2 mL blood sample was obtained intravenously for the LDR for SNP analysis. The 6 SNP loci of LAMA1 were selected and examined. We analyzed the association of several genetic models of 6 LAMA1 SNP loci, sex, age, smoking and drinking status, and the occurrence of esophageal squamous cell carcinoma. Results. In the rs62081531 G > A locus, genotype GA was a protective factor for ESCC compared with GG (OR: 0.830, P = 0.046), especially among the younger and nondrinkers. At rs607230 T > C, genotype TC was linked with a lower risk of ESCC compared with TT. (OR: 0.613, P = 0.034). Haplotype Frequencies revealed that Ars62081531Grs621993Ars539713Trs566655Ars73938538Crs607230 (OR: 0.803, P = 0.028) and Grs62081531Grs621993Ars539713Trs566655Crs73938538Crs607230 (OR: 0.679, P = 0.010) were strongly associated with lower susceptibility of ESCC. Conclusion. The LAMA1 rs62081531, rs539713, rs566655, and rs607230 polymorphisms were demonstrated to be related to susceptibility to ESCC in the Chinese population. LAMA1 SNPs may have a significant impact on the occurrence of esophageal cancer and may serve as potential diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Circular RNAs (CircRNAs) are a class of noncoding RNAs formed by backsplicing during cotranscriptional and posttranscriptional processes, and they widely exist in various organisms. CircRNAs have multiple biological functions and are associated with the occurrence and development of many diseases. While the biogenesis and biological function of circRNAs have been extensively studied, there are few studies on circRNA degradation and only a few pathways for specific circRNA degradation have been identified. Here we outline basic information about circRNAs, summarize the research on the circRNA degradation mechanisms and discusses where this field might head, hoping to provide some inspiration and guidance for scholars who aim to study the degradation of circRNAs. In this Perspective, Longxin Ren and co-authors summarise the role of circular RNAs in disease and discuss recent insights into how circular RNAs are metabolised in the cell. [ABSTRACT FROM AUTHOR]

Purpose: Macrophages (MΦs) play a dual role in the promotion and suppression of lung adenocarcinoma (LUAD), the function of which is influenced by the metabolic status. The role of protein tyrosine phosphatase receptor type F (PTPRF) in cancer has not been elucidated, and its role in MΦs remains to be seen. Methods: The Seahorse XFe 96 Cell Flow Analyzer detected glucose metabolism in tumor cells and macrophages. The expressions of FSCN1, M-CSF, IL4, PTPRF and IGF1 in macrophages were detected by Western blotting and qRT-PCR. Binding of FSCN1 and IGF1R was detected by co-immunoprecipitation. The tumor status in animals was observed using the IVIS Lumina III imaging system. Results: We found that Fascin Actin-Bundling Protein 1 (FSCN1) activates the PI3K-AKT and JAK-STAT signaling pathways in LUAD cells via binding to IGF-1R, thereby promoting the secretion of cytokines such as IL4 and M-CSF. IL4 and M-CSF promote the expression of PTPRF in MΦs, leading to M2 polarization of MΦs by increasing glucose intake and lactate production. In return, M2-type MΦs act on LUAD cells by secreting cytokines such as IGF-1, CCL2, and IL10, which ultimately promote tumor progression. In vivo experiments proved that the knockdown of FSCN1 in A549 cells and PTPRF in MΦs greatly reduced LUAD proliferative and metastatic capacity, which was consistent with the in vitro findings. Conclusions: This study investigated the reprogramming effects of FSCN1 and PTPRF on inflammatory cytokines in the LUAD microenvironment, revealing potential mechanisms by which FSCN1 and PTPRF promote tumor progression and providing a new experimental basis for LUAD treatment. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240).Methods: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events.Discussion: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021.Trial Registration: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered. [ABSTRACT FROM AUTHOR]

Background: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). Methods: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. Results: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2–3] days vs. 3 [3–4] days, p = 0.001), but comparable LOS (10 [9–11.25] days vs. 10 [9–13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). Conclusions: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE. [ABSTRACT FROM AUTHOR]

Purpose: Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy. Methods: Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes in pulmonary function, operative data, and pulmonary complications were compared between the 2 groups. Results: A total of 71 patients were randomized and underwent MIE after receiving CT (n = 34) or CRT (n = 37). Baseline clinical characteristics were comparable between the 2 groups. The CRT group experienced a greater decrease of forced expiratory volume at 1 s (FEV1) (2.66 to 2.18 L, p = 0.023) and diffusion capacity of the lung for carbon monoxide divided by the mean alveolar volume (DLCO/Va) (17.3%, p < 0.001) than the CT group (FEV1 2.53 to 2.41 L; DLCO/Va 4.8%). The incidence of pulmonary complications was higher in the CRT group (13.51 vs. 8.82%), but the difference was not significant (p = 0.532). Conclusions: Preoperative CRT affects pulmonary function more than CT alone, but does not increase the risk of pulmonary complications in patients undergoing MIE. [ABSTRACT FROM AUTHOR]

Studying the fragmentation and refinement of diamond powder as well as the diversification in the intergranular stress is crucial to produce a high-quality polycrystalline diamond. In this paper, using different micron-size diamond powders as the initial materials, the samples were compressed under different pressures at ambient temperature. The fragmentation behavior of the diamond powder was investigated by scanning electron microscopy and with a laser particle size analyzer. The results show that the fragmentation of diamond comprises three stages with increasing pressure: (i) fracturing of edges and corners, (ii) cracking of the crystal plane, and (iii) refinement of particle disorder; the particle deformation tends to become relatively stable after a certain pressure. In situ high-pressure synchrotron X-ray diffraction was used to study the intergranular stress distribution under non-hydrostatic compression to 35.1 GPa. A heterogeneous stress distribution was found in compressed diamond bulk, in which under the highest load, the maximum stress reached 69.5 GPa, whereas the minimum stress was only 18.8 GPa. [ABSTRACT FROM AUTHOR]

Background: The defects and imbalance in lung repair and structural maintenance contribute to the pathogenesis of chronic obstructive pulmonary diseases (COPD), yet the molecular mechanisms that regulate lung repair process are so far incompletely understood. We hypothesized that cigarette smoking causes glycocalyx impairment and endothelial apoptosis in COPD, which could be repaired by the stimulation of fibroblast growth factor 10 (FGF10)/FGF receptor 1 (FGFR1) signaling.Methods: We used immunostaining (immunohistochemical [IHC] and immunofluorescence [IF]) and enzyme-linked immunosorbent assay (ELISA) to detect the levels of glycocalyx components and endothelial apoptosis in animal models and in patients with COPD. We used the murine emphysema model and in vitro studies to determine the protective and reparative role of FGF10/FGFR1.Results: Exposure to cigarette smoke caused endothelial glycocalyx impairment and emphysematous changes in murine models and human specimens. Pretreatment of FGF10 attenuated the development of emphysema and the shedding of glycocalyx components induced by CSE in vivo. However, FGF10 did not attenuate the emphysema induced by endothelial-specific killing peptide CGSPGWVRC-GG-D(KLAKLAK)2. Mechanistically, FGF10 alleviated smoke-induced endothelial apoptosis and glycocalyx repair through FGFR1/ERK/SOX9/HS6ST1 signaling in vitro. FGF10 was shown to repair pulmonary glycocalyx injury and endothelial apoptosis, and attenuate smoke-induced COPD through FGFR1 signaling.Conclusions: Our results suggest that FGF10 may serve as a potential therapeutic strategy against COPD via endothelial repair and glycocalyx reconstitution. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal squamous cell carcinoma (ESCC) is a prevalent tumor in the gastrointestinal tract, but our understanding of the molecular mechanisms underlying ESCC remains incomplete. Existing studies indicate that SUMO specific peptidase 1 (SENP1) plays a crucial role in the development and progression of various malignant tumors through diverse molecular mechanisms. However, the functional mechanism and clinical implications of SENP1 in the progression of ESCC remain unclear.Bulk RNA-Sequencing (RNA-seq) was used to compare potential genes in the esophageal tissues of mice with ESCC to the control group. The up-regulated SENP1 was selected. The protein level of SENP1 in ESCC patient samples was analyzed by immunohistochemistry and western blot. The potential prognostic value of SENP1 on overall survival of ESCC patients was examined using tissue microarray analysis and the Kaplan-Meier method. The biological function was confirmed through in vitro and in vivo knockdown approaches of SENP1. The role of SENP1 in cell cycle progression and apoptosis of ESCC cells was analyzed by flow cytometry and western blot. The downstream signaling pathways regulated by SENP1 were investigated via using RNA-Seq. SENP1-associated proteins were identified through immunoprecipitation. Overexpression of Sirtuin 6 (SIRT6) wildtype and mutant was performed to investigate the regulatory role of SENP1 in ESCC progression in vitro.Our study discovered that SENP1 was upregulated in ESCC tissues and served as a novel prognostic factor. Moreover, SENP1 enhanced cell proliferation and migration of ESCC cell lines in vitro, as well as promoted tumor growth in vivo. Thymidine kinase 1 (TK1), Geminin (GMNN), cyclin dependent kinase 1(CDK1), and cyclin A2 (CCNA2) were identified as downstream genes of SENP1. Mechanistically, SENP1 deSUMOylated SIRT6 and subsequently inhibited SIRT6-mediated histone 3 lysine 56 (H3K56) deacetylation on those downstream genes. SIRT6 SUMOylation mutant (4KR) rescued the growth inhibition upon SENP1 depletion.SENP1 promotes the malignant progression of ESCC by inhibiting the deacetylase activity of SIRT6 pathway through deSUMOylation. Our findings suggest that SENP1 may serve as a valuable biomarker for prognosis and a target for therapeutic intervention in ESCC.Methods: Esophageal squamous cell carcinoma (ESCC) is a prevalent tumor in the gastrointestinal tract, but our understanding of the molecular mechanisms underlying ESCC remains incomplete. Existing studies indicate that SUMO specific peptidase 1 (SENP1) plays a crucial role in the development and progression of various malignant tumors through diverse molecular mechanisms. However, the functional mechanism and clinical implications of SENP1 in the progression of ESCC remain unclear.Bulk RNA-Sequencing (RNA-seq) was used to compare potential genes in the esophageal tissues of mice with ESCC to the control group. The up-regulated SENP1 was selected. The protein level of SENP1 in ESCC patient samples was analyzed by immunohistochemistry and western blot. The potential prognostic value of SENP1 on overall survival of ESCC patients was examined using tissue microarray analysis and the Kaplan-Meier method. The biological function was confirmed through in vitro and in vivo knockdown approaches of SENP1. The role of SENP1 in cell cycle progression and apoptosis of ESCC cells was analyzed by flow cytometry and western blot. The downstream signaling pathways regulated by SENP1 were investigated via using RNA-Seq. SENP1-associated proteins were identified through immunoprecipitation. Overexpression of Sirtuin 6 (SIRT6) wildtype and mutant was performed to investigate the regulatory role of SENP1 in ESCC progression in vitro.Our study discovered that SENP1 was upregulated in ESCC tissues and served as a novel prognostic factor. Moreover, SENP1 enhanced cell proliferation and migration of ESCC cell lines in vitro, as well as promoted tumor growth in vivo. Thymidine kinase 1 (TK1), Geminin (GMNN), cyclin dependent kinase 1(CDK1), and cyclin A2 (CCNA2) were identified as downstream genes of SENP1. Mechanistically, SENP1 deSUMOylated SIRT6 and subsequently inhibited SIRT6-mediated histone 3 lysine 56 (H3K56) deacetylation on those downstream genes. SIRT6 SUMOylation mutant (4KR) rescued the growth inhibition upon SENP1 depletion.SENP1 promotes the malignant progression of ESCC by inhibiting the deacetylase activity of SIRT6 pathway through deSUMOylation. Our findings suggest that SENP1 may serve as a valuable biomarker for prognosis and a target for therapeutic intervention in ESCC.Results: Esophageal squamous cell carcinoma (ESCC) is a prevalent tumor in the gastrointestinal tract, but our understanding of the molecular mechanisms underlying ESCC remains incomplete. Existing studies indicate that SUMO specific peptidase 1 (SENP1) plays a crucial role in the development and progression of various malignant tumors through diverse molecular mechanisms. However, the functional mechanism and clinical implications of SENP1 in the progression of ESCC remain unclear.Bulk RNA-Sequencing (RNA-seq) was used to compare potential genes in the esophageal tissues of mice with ESCC to the control group. The up-regulated SENP1 was selected. The protein level of SENP1 in ESCC patient samples was analyzed by immunohistochemistry and western blot. The potential prognostic value of SENP1 on overall survival of ESCC patients was examined using tissue microarray analysis and the Kaplan-Meier method. The biological function was confirmed through in vitro and in vivo knockdown approaches of SENP1. The role of SENP1 in cell cycle progression and apoptosis of ESCC cells was analyzed by flow cytometry and western blot. The downstream signaling pathways regulated by SENP1 were investigated via using RNA-Seq. SENP1-associated proteins were identified through immunoprecipitation. Overexpression of Sirtuin 6 (SIRT6) wildtype and mutant was performed to investigate the regulatory role of SENP1 in ESCC progression in vitro.Our study discovered that SENP1 was upregulated in ESCC tissues and served as a novel prognostic factor. Moreover, SENP1 enhanced cell proliferation and migration of ESCC cell lines in vitro, as well as promoted tumor growth in vivo. Thymidine kinase 1 (TK1), Geminin (GMNN), cyclin dependent kinase 1(CDK1), and cyclin A2 (CCNA2) were identified as downstream genes of SENP1. Mechanistically, SENP1 deSUMOylated SIRT6 and subsequently inhibited SIRT6-mediated histone 3 lysine 56 (H3K56) deacetylation on those downstream genes. SIRT6 SUMOylation mutant (4KR) rescued the growth inhibition upon SENP1 depletion.SENP1 promotes the malignant progression of ESCC by inhibiting the deacetylase activity of SIRT6 pathway through deSUMOylation. Our findings suggest that SENP1 may serve as a valuable biomarker for prognosis and a target for therapeutic intervention in ESCC.Conclusions: Esophageal squamous cell carcinoma (ESCC) is a prevalent tumor in the gastrointestinal tract, but our understanding of the molecular mechanisms underlying ESCC remains incomplete. Existing studies indicate that SUMO specific peptidase 1 (SENP1) plays a crucial role in the development and progression of various malignant tumors through diverse molecular mechanisms. However, the functional mechanism and clinical implications of SENP1 in the progression of ESCC remain unclear.Bulk RNA-Sequencing (RNA-seq) was used to compare potential genes in the esophageal tissues of mice with ESCC to the control group. The up-regulated SENP1 was selected. The protein level of SENP1 in ESCC patient samples was analyzed by immunohistochemistry and western blot. The potential prognostic value of SENP1 on overall survival of ESCC patients was examined using tissue microarray analysis and the Kaplan-Meier method. The biological function was confirmed through in vitro and in vivo knockdown approaches of SENP1. The role of SENP1 in cell cycle progression and apoptosis of ESCC cells was analyzed by flow cytometry and western blot. The downstream signaling pathways regulated by SENP1 were investigated via using RNA-Seq. SENP1-associated proteins were identified through immunoprecipitation. Overexpression of Sirtuin 6 (SIRT6) wildtype and mutant was performed to investigate the regulatory role of SENP1 in ESCC progression in vitro.Our study discovered that SENP1 was upregulated in ESCC tissues and served as a novel prognostic factor. Moreover, SENP1 enhanced cell proliferation and migration of ESCC cell lines in vitro, as well as promoted tumor growth in vivo. Thymidine kinase 1 (TK1), Geminin (GMNN), cyclin dependent kinase 1(CDK1), and cyclin A2 (CCNA2) were identified as downstream genes of SENP1. Mechanistically, SENP1 deSUMOylated SIRT6 and subsequently inhibited SIRT6-mediated histone 3 lysine 56 (H3K56) deacetylation on those downstream genes. SIRT6 SUMOylation mutant (4KR) rescued the growth inhibition upon SENP1 depletion.SENP1 promotes the malignant progression of ESCC by inhibiting the deacetylase activity of SIRT6 pathway through deSUMOylation. Our findings suggest that SENP1 may serve as a valuable biomarker for prognosis and a target for therapeutic intervention in ESCC. [ABSTRACT FROM AUTHOR]

Metformin has been found to have inhibitory effects on a variety of tumors. However, its effects on non-small cell lung cancer (NSCLC) remain unclear. We demonstrated that metformin could inhibit the proliferation of A549 and H1299 cells. RNA transcriptome sequencing revealed that PDL1 was significantly downregulated in both cell types following treatment with metformin (P < 0.001). Jaspar analysis and chromatin immunoprecipitation showed that CEBPB could directly bind the promoter region of PDL1. Western blotting showed that protein expression of the isoforms CEBPB-LAP*, CEBPB-LAP, and CEBPB-LIP was significantly upregulated and the LIP/LAP ratio was increased. Gene chip analysis showed that PDL1 was significantly upregulated in A549-CEBPB-LAP cells and significantly downregulated in A549-CEBPB-LIP cells (P < 0.05) compared with CEBPB-NC cells. Dual-luciferase reporter gene assay showed that CEBPB-LAP overexpression could promote transcription of PDL1 and CEBPB-LIP overexpression could inhibit the process. Functional assays showed that the changes in CEBPB isoforms affected the function of NSCLC cells. Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK–CEBPB–PDL1 signaling. Animal experiments showed that tumor growth was significantly inhibited by metformin, and atezolizumab and metformin had a synergistic effect on tumor growth. A total of 1247 patients were retrospectively analyzed, including 166 and 1081 patients in metformin and control groups, respectively. The positive rate of PDL1 was lower than that of the control group (HR = 0.338, 95% CI = 0.235–0.487; P < 0.001). In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK–CEBPB–PDL1 signaling-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240). Methods: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events. Discussion: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021. Trial registration: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered. [ABSTRACT FROM AUTHOR]

Background: Open esophagectomy (OE) in elderly patients with esophageal cancer is hazardous due to high surgical mortality and limited survival. The aim of this study was to explore whether minimally invasive esophagectomy (MIE) has perioperative or long-term benefits in elderly patients with esophageal cancer compared with OE. Methods: Between February 2005 and June 2013, 407 patients older than 70 years underwent esophagectomy for esophageal cancer, including 89 who received MIE and 318 who received OE. A retrospective pair-matched study was performed to compare 116 patients (58 pairs) who underwent either OE or MIE. Patients were matched by age, sex, comorbidity, tumor location, histology, TNM stage, and operative approach. Perioperative and long-term outcomes were compared between the two groups. Results: The overall incidence of postoperative complications was significantly lower in the MIE group than in the OE group (37.9 vs. 60.3 %, P = 0.016), especially incidence of pulmonary complications (20.7 vs. 39.7 %, P = 0.026). The mean length of hospital stay was also significantly shorter (10 days [range 7-70] vs. 12 days [range 8-106], P = 0.032). The perioperative mortality rate trended lower in the MIE group but was not significantly different (3.4 vs. 8.6 %, P = 0.435). Kaplan-Meier analysis showed that the median disease-specific survival time in the MIE group was significantly longer than in the OE group (>27 months [range 1-82] vs. 24 months [range 1-99], P = 0.003). No difference was found in overall survival (39 ± 8.9 vs. 22 ± 3.4 months, P = 0.070). Conclusion: In surgical management of elderly patients with esophageal cancer, MIE is associated with lower rates of morbidity and pulmonary complications as well as longer disease-specific survival time. Whether it provides benefit to patients' long-term survival requires further research. [ABSTRACT FROM AUTHOR]

Objectives: Platinum-based chemotherapies are currently the first-line treatment of non-small cell lung cancer. This study will improve our understanding of the causes of resistance to cisplatin, especially in lung adenocarcinoma (LUAD) and provide a reference for therapeutic decisions in clinical practice.Methods: Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA) and Zhongshan hospital affiliated to Fudan University (zs-cohort) were used to identify the multi-omics differences related to platinum chemotherapy. Cisplatin-resistant mRNA and miRNA models were constructed by Logistic regression, classification and regression tree and C4.5 decision tree classification algorithm with previous feature selection performed via least absolute shrinkage and selection operator (LASSO). qRT-PCR and western-blotting of A549 and H358 cells, as well as single-cell Seq data of tumor samples were applied to verify the tendency of certain genes.Results: 661 cell lines were divided into three groups according to the IC50 value of cisplatin, and the top 1/3 (220) with a small IC50 value were defined as the sensitive group while the last 1/3 (220) were enrolled in the insensitive group. TP53 was the most common mutation in the insensitive group, in contrast to TTN in the sensitive group. 1348 mRNA, 80 miRNA, and 15 metabolites were differentially expressed between 2 groups (P < 0.05). According to the LASSO penalized logistic modeling, 6 of the 1348 mRNAs, FOXA2, BATF3, SIX1, HOXA1, ZBTB38, IRF5, were selected as the associated features with cisplatin resistance and for the contribution of predictive mRNA model (all of adjusted P-values < 0.001). Three of 6 (BATF3, IRF5, ZBTB38) genes were finally verified in cell level and patients in zs-cohort.Conclusions: Somatic mutations, mRNA expressions, miRNA expressions, metabolites and methylation were related to the resistance of cisplatin. The models we created could help in the prediction of the reaction and prognosis of patients given platinum-based chemotherapies. [ABSTRACT FROM AUTHOR]

• Part-solid nodules and pure-solid nodules show different clinicopathological characteristics, especially in SUVmax. • SUVmax predicts lung adenocarcinoma with any amount of solid or micropapillary component. • SUVmax can also predict lymph node metastasis for pure-solid nodules. • SUVmax is significantly related to 5-year relapse-free and overall survival in patients with tumor size ≤ 2 cm and CTR > 0.5. This study was conducted to explore the clinical significance of the maximum standard uptake value (SUVmax) in the clinical stage IA lung adenocarcinoma with tumor size ≤ 2 cm and consolidation to tumor ratio (CTR) > 0.5. We retrospectively reviewed non-small cell lung cancer patients who underwent surgeries between January 2014 and March 2017. Clinical stage IA lung adenocarcinoma patients with tumor of size ≤ 2 cm and CTR > 0.5 were enrolled. The patients were divided into two groups: part-solid and pure-solid based on whether CTR = 1.0 or not. Nodules with any amount of solid or micropapillary components were regarded as the high-risk subtype. Time-dependent ROC curve was used to determine the best cut-off value. Finally, we analyzed the relationship between SUVmax, high-risk subtypes, node metastasis and 5-year relapse-free survival and overall survival. Totally, 270 patients were included. The distribution of pathological subtypes (p < 0.001), SUVmax (p < 0.001), and pathological N stage (p < 0.001) were different between the two groups. Multivariable analysis indicated that SUVmax could predict high-risk subtypes in cases of part-solid nodules (p < 0.001) and both high-risk subtypes (p = 0.022) and node metastasis (p < 0.001) in cases of pure-solid ones. SUVmax ≥ 2.6 and SUVmax ≥ 5.1 were strongly associated with 5-year relapse-free survival (p < 0.001) and 5-year overall survival (p < 0.001) among all the patients, respectively. Part-solid nodules with 0.5 < CTR < 1 and pure-solid nodules in lung adenocarcinoma show different clinicopathological characteristics, especially in SUVmax. SUVmax is significantly associated with high-risk subtypes, node metastasis, 5-year relapse-free survival and overall survival. [ABSTRACT FROM AUTHOR]

Background: Metabolic reprogramming and redox homeostasis contribute to esophageal squamous cell carcinoma (ESCC). CDC‐like kinase 4 (CLK4) is a dual‐specificity kinase that can phosphorylate substrates' tyrosine or serine/threonine residue. However, the role and mechanism of CLK4 in ESCC remain unknown. Methods: CLK4 expression was analysed using publicly available datasets and confirmed in ESCC tissues and cell lines. The biological roles of CLK4 were studied with gain and loss‐of‐function experiments. Mass spectrometry was employed to examine the effects of CLK4 on metabolic profiling. In vitro kinase assay, co‐immunoprecipitation, glutathione S‐transferase pulldown, chromatin immunoprecipitation and luciferase reporter were used to elucidate the relationship among CLK4, microphthalmia‐associated transcription factor (MITF), COP1 and ZRANB1. Results: CLK4 down‐regulation was observed in ESCC cell lines and clinical samples and associated with the methylation of its promoter. Low levels of CLK4 promoted ESCC development by affecting the purine synthesis pathway and nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide phosphate (NADP+) ratio. Interestingly, CLK4 inhibited ESCC development by blocking MITF‐enhanced de novo purine synthesis and redox balance. Mechanistically, wild type CLK4 (WT‐CLK4) but not kinase‐dead CLK4‐K189R mutant phosphorylated MITF at Y360. This modification promoted its interaction with E3 ligase COP1 and its K63‐linked ubiquitination at K308/K372, leading to sequestosome 1 recognition and autophagic degradation. However, the deubiquitinase ZRANB1 rescued MITF ubiquitination and degradation. In turn, MITF bound to E‐ rather than M‐boxes in CLK4 promoter and transcriptionally down‐regulated its expression in ESCC. Clinically, the negative correlations were observed between CLK4, MITF, and purine metabolic markers, which predicts a poor clinical outcome of ESCC patients. Notably, CLK4 itself was a redox‐sensitive kinase, and its methionine oxidation at M307 impaired kinase activity, enhanced mitochondria length and inhibited lipid peroxidation, contributing to ESCC. Conclusions: Our data highlight the potential role of CLK4 in modulating redox status and nucleotide metabolism, suggesting potential therapeutic targets in ESCC treatment. [ABSTRACT FROM AUTHOR]

Background: Most cancer cells have fundamentally different metabolic characteristics, particularly much higher glycolysis rates than normal tissues, which support the increased demand for biosynthesis and promote tumor progression. We found that transforming growth factor (TGF)-β plays a dual function in regulating glycolysis and cell proliferation in non-small cell lung cancer. Methods: We used the PET/MRI imaging system to observe the glucose metabolism of subcutaneous tumors in nude mice. Energy metabolism of non-small cell lung cancer cell lines detected by the Seahorse XFe96 cell outflow analyzer. Co-immunoprecipitation assays were used to detect the binding of Smads and HIF-1α. Western blotting and qRT-PCR were used to detect the regulatory effects of TGF-β and HIF-1α on c-MYC, PKM1/2, and cell cycle-related genes. Results: We discovered that TGF-β could inhibit glycolysis under normoxia while significantly promoting tumor cells' glycolysis under hypoxia in vitro and in vivo. The binding of hypoxia-inducible factor (HIF)-1α to the MH2 domain of phosphorylated Smad3 switched TGF-β function to glycolysis by changing Smad partners under hypoxia. The Smad-p107-E2F4/5 complex that initially inhibited c-Myc expression was transformed into a Smad-HIF-1α complex that promoted the expression of c-Myc. The increased expression of c-Myc promoted alternative splicing of PKM to PKM2, resulting in the metabolic reprogramming of tumor cells. In addition, the TGF-β/Smad signal lost its effect on cell cycle regulatory protein p15/p21. Furthermore, high expression of c-Myc inhibited p15/p21 and promoted the proliferation of tumor cells under hypoxia. Conclusions: Our results indicated that HIF-1α functions as a critical factor in the dual role of TGF-β in tumor cells, and may be used as a biomarker or therapeutic target for TGF-β mediated cancer progression. [ABSTRACT FROM AUTHOR]

Introduction: Recent advances in thoracoscopic surgery have made it possible to perform esophagectomy with conventional lymphadenectomy (paraesophageal and subcarinal lymph node dissection) using minimally invasive techniques. However, minimally invasive esophagectomy (MIE) combined with extensive lymphadenectomy along the recurrent laryngeal nerves (RLN) has remained technically challenging for thoracic surgeons. The aim of this study was to examine the safety and efficacy of extensive lymphadenectomy when compared to conventional lymphadenectomy during MIE. Methods: We retrospectively reviewed data from a cohort of 147 consecutive patients who underwent MIE for esophageal cancer (EC) over a 3-year period at our institution. During thoracoscopic esophagectomy, extensive lymphadenectomy along the RLN was performed on 76 patients from June 2009 to December 2010 (group A), while 71 patients underwent conventional lymphadenectomy from June 2008 to May 2009 (group B) and were enrolled as historical controls. Clinical characteristics including patient demographics, operation features, and the rate and type of complications were recorded for both groups. The number of dissected lymph nodes and the number of patients with nodes positive for cancer on histological examination were determined for both groups. Statistical analysis was used to identify differences between the two groups. Results: All patients underwent thoracoscopic esophagectomy without conversion to open thoracotomy. Patient demographics and operation features were similar between the two groups. Of the 76 patients that underwent extensive lymphadenectomy there were 13 patients (17.11%) who were RLN positive, which resulted in upstaging of TNM in 5 patients (6.58%). The overall incidence of postoperative complications (42.10% versus 39.47%, p = 0.742) and permanent recurrent laryngeal nerve palsy (1.32% versus 0%, p = 0.517) was similar between the two groups. Conclusions: Extensive mediastinal lymphadenectomy during minimally invasive esophagectomy is a feasible procedure for EC patients. It is technically safe and oncologically adequate in experienced hands, and improves the accuracy of tumor staging. Further study is required to discuss its long-term prognostic value for esophagus cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC). Methods: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Kaplan–Meier curves with log-rank tests were used to evaluate survival. Results: We identified 8 (1.5%), 35(6.7%) and 109 (20.8%) cases with a NTRK1 rearrangement using 15%, 10% and 5% as cut-off values, respectively. We observed copy number (CN) variation of NTRK1 in some cases: 79 (15.1%) cases had a gain in NTRK1 CN ≥ 3, and 24 (4.6%) cases had NTRK1 CN ≥ 4. A NTRK1 rearrangement at the above-mentioned thresholds was not related to disease-free survival (DFS, P = 0.45, 0.47, 0.87) and overall survival (OS, P = 0.80, 0.74, 0.57), respectively. Gain in NTRK1 CN was associated with a poor prognosis irrespective of whether NTRK1 CN ≥ 4 (DFS, P = 0.015; OS, P = 0.035) or NTRK1 CN ≥ 3 (DFS, P = 0.039; OS, P = 0.025). Conclusion: A NTRK1 rearrangement occurred rarely in ESCC. The increased CN of NTRK1 might be a prognostic indicator for DFS and OS in patients with ESCC. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is one of the most common types of cancer and has a low survival rate. β-1,4- N -Acetyl galactosaminyltransferase 1 (B4GALNT1), which is involved in the synthesis of complex gangliosides, is highly expressed in the progression of various cancers. This study aimed to elucidate the biological functions of B4GALNT1 in LUAD progression and metastasis. We observed that B4GALNT1 overexpression showed enhanced cell migration and invasion in vitro , and promoted tumor metastasis, with reduced survival in mice. Mechanistically, B4GALNT1 regulated metastatic potential of LUAD through activating the JNK/c-Jun/Slug pathway, and with the form of its enzymatic activity. Clinical samples confirmed that B4GALNT1 expression was upregulated in LUAD, and B4GALNT1 was correlated with c-Jun/Slug expression, lymph node involvement, advanced clinical stage, and reduced overall survival. Collectively, our results suggest that B4GALNT1 promotes progression and metastasis of LUAD through activating JNK/c-Jun/Slug signaling, and with the form of its enzymatic activity. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) patients with different American Joint Committee on Cancer stages have different overall 5‐year survival rates. The tumor microenvironment (TME) and intra‐tumor heterogeneity (ITH) have been shown to play a crucial role in the occurrence and development of tumors. However, the TME and ITH in different lesions of LUAD have not been extensively explored. Methods: We present a 204,157‐cell catalog of the TME transcriptome in 29 lung samples to systematically explore the TME and ITH in the different stages of LUAD. Traditional RNA sequencing data and complete clinical information were downloaded from publicly available databases. Results: Based on these high‐quality cells, we constructed a single‐cell network underlying cellular and molecular features of normal lung, early LUAD, and advanced LUAD cells. In contrast with early malignant cells, we noticed that advanced malignant cells had a remarkably more complex TME and higher ITH level. We also found that compared with other immune cells, more differences in CD8+/CTL T cells, regulatory T cells, and follicular B cells were evident between early and advanced LUAD. Additionally, cell‐cell communication analyses, revealed great diversity between different lesions of LUAD at the single‐cell level. Flow cytometry and qRT‐PCR were used to validate our results. Conclusion: Our results revealed the cellular diversity and molecular complexity of cell lineages in different stages of LUAD. We believe our research, which serves as a basic framework and valuable resource, can facilitate exploration of the pathogenesis of LUAD and identify novel therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

Esophageal carcinoma stem cells (ECSCs) are responsible for the initiation and therapy-resistance of esophageal cancer. Nutrient sensor O-GlcNAc transferase (OGT) promoted the growth and metastasis of cancer cells. However, the contributions of OGT to the tumorigenesis of ECSCs remain largely uncover. In the present study, as compared to matched non-stem cancer cells, the expression of OGT was higher in ALDH+ ECSCs. Knock down of OGT by lentivirus system reduced the self-renewal capacities and tumorigenicity of ALDH+ ECSCs. In addition, OGT in exosome derived from ALDH+ ECSCs was taken up by neighboring CD8+ T cells and increased the expression of PD-1 in CD8+ T cells. Down-regulation of OGT increased the apoptosis of ALDH+ ECSCs induced by CD8+ T cells, which could be blocked by overexpression of PD-1 in CD8+ T cells. Together, OGT in exosome from ECSCs protects ECSCs from CD8+ T cells through up-regulation of PD-1. [ABSTRACT FROM AUTHOR]

Background: We assessed visual residual tumour cells (VRTC) with both Becker's tumour regression grading (TRG) system and Japanese TRG system in esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant therapy followed by surgery.Methods: We compared Becker system and Japanese system in 175 ESCC patients treated between 2009 and 2015.Results: According to Becker system, the 5-year DFS/DSS rates were 70.0%/89.3, 53.8%/56.7, 43.0%/49.0, and 42.4%/39.1% for TRG 1a (VRTC 0), TRG 1b (1-10%), TRG 2 (11-50%), and TRG 3 (> 50%). According to Japanese system, the rates were 38.8%/34.1, 49.5%/58.7, 50.2%/49.0 and 70.0%/89.3% for Grade 0-1a (VRTC> 66.6%), Grade 1b (33.3-66.6%), Grade 2 (1-33.3%) and Grade 3 (0). TRG according to two systems significantly discriminate the patients' prognosis. TRG according to Becker system (HR 2.662, 95% CI 1.151-6.157), and lymph node metastasis (HR 2.567, 95% CI 1.442-4.570) were independent parameters of DSS.Conclusions: Both Becker and Japanese system had their advantage in risk stratification of these ESCC patients. It was speculated that dividing 1-10% VRTC into a group might contribute to independently prognostic significance of Becker's TRG system. Therefore, in addition to TRG of different systems, the percentage of VRTC might be recommended in the pathologic report, which could make the results more comparable among different researches, and more understandable for oncologists in the clinical practice. [ABSTRACT FROM AUTHOR]

Until now, neoadjuvant therapy plus surgical resection of the primary tumor and potential metastatic lymph nodes (LNs) has been the current optimal treatment for locally advanced thoracic esophageal cancer (EC). LN metastasis is one of the most negative prognostic factors for thoracic esophageal squamous cell carcinoma (ESCC). However, the extent of LN dissection for thoracic ESCC has long been controversial worldwide. LNs along the recurrent laryngeal nerve (RLN) were reported to have the highest frequency of metastases in thoracic ESCC, so lymphadenectomy along the bilateral RLN is necessary but quite challenging because of a high frequency of recurrent nerve palsy and related postoperative complications. With the development of minimally invasive devices and techniques in recent years, minimally invasive esophagectomy (MIE) has been widely applied in EC surgery. The topics of what the optimal extent of lymphadenectomy is and how the recurrent nerve should be well protected during MIE have been debated in recent years. The purpose of our review is specifically to address the patterns of LN metastasis, the extent of LN dissection, and the protection of the RLN in MIE for thoracic ESCC. [ABSTRACT FROM AUTHOR]

Background: Esophagectomy is still advised as an additional treatment for pathological T1b (pT1b) esophageal squamous cell carcinoma (ESCC) following attempted endoscopic resection (ER). ER followed with definitive chemoradiotherapy (dCRT) has shown increased quality of life as well as comparable oncological outcomes to esophagectomy. However, there is no well-designed phase III trial to compare the two treatments for patients with pT1b ESCC.Methods: One hundred seventy-six patients with clinical stage N0 (cN0) and pT1b ESCC will be recruited at three centers and randomly assigned to the esophagectomy group or the dCRT group. The clinical lymph node status will be measured by image examination, including computer tomography and positron emission tomography-computed tomography. The pathological tumor status will be diagnosed after endoscopic submucosal dissection (ESD). All patients will be followed up for 60 months after randomization. The primary endpoint is 5-year overall survival. The secondary endpoints are quality of life, related adverse events, 3-year overall survival, and relapse-free survival rates.Discussion: To the best of our knowledge, this is the first phase III randomized controlled trial to compare esophagectomy and dCRT for patients with cN0-pT1b ESCC after ESD. Based on the results of this study, we will show whether dCRT will benefit patients more than esophagectomy, which will contribute more high-quality evidence to the primary salvage treatment for these patients.Trial Registration: ClinicalTrials.gov, NCT04135664 . Registered on Aug. 10, 2019. [ABSTRACT FROM AUTHOR]

Objective: In this cohort study, we determined the clinical value of the maximum standardized uptake value (SUVmax) of primary tumors in non‐small cell lung cancer (NSCLC). Study Design: A retrospective review of NSCLC patients was performed from January 2011 to December 2017. Peripheral cN0 NSCLC patients with tumor size ≤2 cm were included. SUVmax was calculated as a continuous variable for semiquantitative analyses. A receiver operating characteristic curve was analyzed to assess the cutoff threshold of SUVmax on pathological (p) nodal metastasis. We further evaluated the clinical relevance of SUVmax in peripheral cN0 NSCLC patients. Results: A total of 670 peripheral NSCLC patients with tumor size ≤2 cm were deemed cN0 by preoperative PET/CT scan. Statistical analyses suggested significant correlations of SUVmax with smoking status (P =.026), tumor volume (P =.001), pathology type (P =.008), tumor differentiation (P <.001), vessel invasion (P =.001), plural invasion (P <.001), pT stage (P <.001), nodal involvement (P <.001), and pathological tumor node metastasis stage (P <.001). A cutoff point of SUVmax of 3.8 (P <.001) could be used to predict pathological nodal metastasis. Multivariable analyses indicated that preoperative SUVmax >3.8 (odds ratio, 12.149; P <.001) was an independent predictor of nodal metastasis. Overall survival analyses further suggested that SUVmax was an independent prognostic indicator (hazard ratio, 2.050; P =.017). Conclusion: Preoperative SUVmax is a predictor of pathological nodal metastasis and prognosis for peripheral cN0 NSCLC patients with tumor size ≤2 cm. Our results indicate that assessment of PET SUVmax could improve stratification of these patients. [ABSTRACT FROM AUTHOR]

Hafnium diboride (HfB2) is one of the most promising hard-brittle ceramic materials with unique physical properties. Here, we have synthesized the well-crystallized HfB2 by a high-pressure solid-state reaction and employ in situ high-pressure synchrotron radiation angle-dispersive X-ray diffraction to investigate the size-effect of HfB2. An abnormal physical behavior of HfB2 under high pressure is observed. The microsized HfB2 shows slight anisotropy along a and c axes; however, the nanosized HfB2 reveals a different compression behavior with pressure-induced shell structural transition from a disordered symmetric amorphous shell state to an asymmetric amorphous shell state. In addition, the results indicate that the pressure calibrations are sensitive to the grain size. The present findings offer insights into the physical behaviors of different sized HfB2, which may also provide valuable information for other transition metal borides under high pressure. [ABSTRACT FROM AUTHOR]

Recently, underwater glider has become an effective tool for long-term ocean exploration. Controllable wing technology, which can improve comprehensive performance of underwater glider, has received widespread attention. This paper mainly proposes a multi-objective optimization based design method of controllable wings for underwater gliders. First, controllable wing configuration parameters are determined, specifically including wing span and sweep angle here. Then, hydrodynamic equations, containing controllable wing configuration parameters, are obtained by CFD simulation and quartic polynomial fitting. On this basis, the glider performance analysis model, quantitatively evaluating voyage velocity, static stability and energy consumption, are derived, and multi-objective optimization model of wing configuration parameters is established. Meanwhile, the relationship between controllable wing configuration parameters and the glider comprehensive performance is discussed. Especially, surrogate model technology is introduced into optimization calculation process to improve optimization efficiency. And non-dominated sorting genetic algorithm II is employed to obtain Pareto optimal set, which will make design objectives of driving mechanism of controllable wings clearer. Based on multi-objective optimization results and linkage synthesis method, a novel driving mechanism of controllable wings is designed, and corresponding principle prototype is manufactured. Besides, the motion characteristic, sealing and locking methods of the design scheme are also discussed. • A multi-objective optimization method for controllable wing configuration parameters of underwater glider. • Multi-objective optimization results make design objectives of driving mechanism of controllable wings clearer. • A novel driving mechanism of controllable wings for underwater glider and its principle prototype. • The effect of controllable wings on the glider comprehensive performance is analyzed. • The motion characteristic, sealing and locking methods of driving mechanism are discussed. [ABSTRACT FROM AUTHOR]

Backgrounds: Since Mesenchymal epithelial transition (MET) amplification has been regarded as a potential treatment target, the knowledge of its prevalence and prognostic importance is crucial. However, its clinical pathologic characteristics are not well known in esophageal squamous cell carcinoma (ESCC).Methods: We investigated MET gene status with fluorescence in situ hybridization (FISH) assay in 495 ESCC cases using tissue microarrays. Prognostic significance as well as correlations with various clinicopathological parameters was evaluated.Results: Among 495 patients, 28 (5.7%) cases were MET FISH positive, including 5 cases (1%) with true gene amplification. There were no statistically significant associations between MET FISH-positivity and clinicopathologic characteristics. A significantly poorer prognosis was observed in 28 patients with MET FISH-positivity (disease free survival/DFS, P < 0.001 and overall survival/OS, P = 0.001). Multivariate analysis revealed MET FISH-positivity was an independent prognostic factor for DFS (hazard ratio/HR, 1.953; 95% confidence interval/CI, 1.271-2.999; P = 0.002) and OS (HR, 1.926; 95% CI, 1.243-2.983; P = 0.003). MET FISH-positivity was associated with DFS (P = 0.022 and 0.020) and OS (P = 0.046 and 0.024) both in stage I-II ESCC and in stage III-IVa ESCC. No statistical significance (DFS, P = 0.492 and OS, P = 0.344) was detected between stage I-II ESCC with MET FISH-positivity and stage III-IVa ESCC with FISH-negativity.Conclusions: Increased MET gene copy number is an independent prognostic factor in ESCC, and ESCC might have potentially been up-staged by increased MET gene copy number. The results indicate that increased MET gene copy number is a very promising parameter, in clinical therapy and follow-up plans. [ABSTRACT FROM AUTHOR]

Histologically node negative esophageal squamous cell carcinoma (pN0 ESCC) after radical resection still carries a significant risk of recurrence, especially in high‐risk patients. Our previous study showed that the risk of recurrence was associated with tumor location and cell differentiation, as well as the presence of lymphovascular invasion. Most recurrence occurs within two years after surgery. There is still a lack of knowledge on the risks or potential benefits of postoperative adjuvant therapies for high‐risk pN0 ESCC patients. This study was designed to evaluate the efficacy and toxicity of adjuvant therapies after radical surgery in high‐risk patients with pN0 ESCC. This study is a multicenter, prospective, controlled randomized trial, which will compare the differences between either adjuvant chemotherapy or adjuvant radiotherapy and surgery alone for high‐risk pN0 ESCC. Patients in group A will receive three cycles of adjuvant chemotherapy with paclitaxel and cisplatin, patients in group B will receive adjuvant radiotherapy with intensity‐modulated radiation of 50 Gy, and patients in group C (the control) will receive surgery alone. The primary endpoint is three‐year disease‐free survival. Secondary endpoints include toxicity of adjuvant therapies and five‐year overall survival. One hundred and sixty‐two patients in each group are required and a total of 486 patients will finally be enrolled into the study. This will be the first randomized trial to investigate the necessity or potential benefit of postoperative adjuvant therapies for high‐risk pN0 ESCC patients. [ABSTRACT FROM AUTHOR]

Underwater gliders are well known as a type of autonomous observation platform of ocean phenomena, which can achieve space motion by low energy consumption. In this paper, we study motion trajectory design methods of underwater gliders executing underwater fixed-point exploration missions. First, performance analysis models of an underwater glider are established, including the dynamic model and the energy consumption model. Then, according to the positions of target exploration points, we divide underwater fixed-point exploration missions into three categories, namely, the short voyage range exploration mission, the moderate voyage range exploration mission, and the long voyage range exploration mission. Based on the glider motion modes of in-profile gliding and spiral gliding, two trajectory design methods are proposed for the above three categories of exploration missions. To achieve the full coverage of target exploration points, we present a net buoyancy compensation strategy of the glider carrying out the spiral motion. Based on the surrogate model technology and a multi-objective optimization algorithm, the optimization method of the glider control parameters is further proposed to design the optimal motion trajectory. Finally, the trajectory design methods are validated by numerical examples. This study can provide certain guidance for the actual application of underwater gliders. • Underwater fixed-point exploration missions (UFEM) of underwater gliders are divided into three categories. • Motion trajectory design for UFEM is achieved using conventional motion modes of underwater gliders. • The proposed methods can achieve the full coverage of target exploration points under specific water depth ranges. • The optimization method of the glider control parameters is proposed to design the optimal glider motion trajectory. [ABSTRACT FROM AUTHOR]

Background The methodology of thromboprophylaxis post minimally invasive esophagectomy (MIE) is unclear. Thus, we compared the efficacy and safety of fondaparinux and nadroparin on the prophylaxis of venous thromboembolism (VTE) after MIE. Materials and methods We conducted a randomized, double-blind, treatment-controlled study. Consecutive patients undergoing MIE randomly received a single dose of either nadroparin 2850 AxaIU (Group H) or fondaparinux 2.5 mg (Group F) daily. We used ultrasonography to identify deep vein thrombosis (DVT) on postoperative day 7. The coagulation status was examined using thromboelastography (TEG) prior to and at 0, 24, 48, and 72 h after the operation. Bleeding events were recorded during anticoagulation therapy and analysis was performed on an intention-to-treat basis. Results We randomly assigned the patients to Group H ( n  = 57) or Group F ( n  = 59). Symptomatic or asymptomatic DVT was identified in seven patients in Group H and one patient in Group F (12.28% vs. 1.69%, p  = 0.031). Pulmonary embolism developed in one patient in Group H, and the VTE incidence was significantly lower in Group F than Group H (1.69% vs. 14.04%, RR: 0.121, 95% CI: 0.016–0.935, p  = 0.016). TEG analysis showed a more inhibited coagulation profile of Group F compared with Group H reflected by the significantly prolonged R time at 48 h and 72 h after operation (6.8 ± 2.2 min vs. 8.4 ± 2.7 min, p  = 0.005; 7.1 ± 1.6 min vs. 9.2 ± 3.7 min, p  = 0.002). Bleeding events were not recorded in either group. Conclusions Fondaparinux could provide similar efficacy and safety in postoperative thromboprophylaxis following MIE compared with nadroparin. [ABSTRACT FROM AUTHOR]

In this study, using MoSi 2 powder as starting material, the bulk MoSi 2 samples were sintered at 1000–1600 °C under 5.5 GPa in a DS6 × 14MN cubic press. Furthermore, their sintering behavior and mechanical properties were investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM) and indentation tests. XRD results elucidate that MoSi 2 can still maintain its body-centered-tetragonal structure after the high pressure and high temperature (HPHT) sintering. SEM images imply the combination between grain growths and re-crystallization. Strong covalent bonding between the grains is crucial for improving the mechanical properties of samples. But re-crystallization results in a large number of pores between grains in the sintered body, so that the density and hardness was reduced. Indentation tests indicate that sintered MoSi 2 have hardness values of 13.6–15.0 GPa, which increase with increasing temperature and is harder than polycrystalline and single crystal MoSi 2 . The results demonstrate that the sintered MoSi 2 at 5.5 GPa/1300 °C possesses outstanding mechanical properties, including a high relative density ( 6.23 g / cm 3 ), Vickers hardness (15.0 GPa) and fracture toughness (10.7 MPa m 1/2 ) at applied load of 29.4 N. In addition, the oxidation resistance of the prepared samples is measured using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis. The results show that the oxidation resistance has been significantly improved from this work compared with polycrystalline MoSi 2 . [ABSTRACT FROM AUTHOR]

In this study, high pressure and high temperature sintering (HPHT) is adopted in the cermet fabrication process, and the microstructure and mechanical properties of cermets with TiC 0.5 N 0.5 –15WC–10Mo 2 C–5TaC–10Ni–10Co (wt%) sintered under 5 GPa and different temperatures (900–1600 °C) using 6 × 14 MN cubic press are investigated. Results show that the densities of samples can reach up to 7.00 g/cm 3 . Vickers hardness and fracture toughness of the products are over 1727 HV30 and 7.2 MPa m 1/2 respectively. In addition, the sintering results are compared with the data that obtained from commercial samples which produced via conventional sintering technique. The conclusion is that high density and high hardness cermets can be obtained through HPHT sintering. [ABSTRACT FROM AUTHOR]

Background: Postoperative chylothorax is a rare, but potentially fatal complication after esophagectomy. Preventive measures aimed at decreasing the incidence of chyle leakage after minimally invasive esophagectomy (MIE) could potentially reduce the high postoperative mortality associated with this complication. However, previous techniques are traumatic and time consuming. We present a simple method in the prophylaxis of chylothorax after MIE. Study Design: A total of 344 consecutive esophageal cancer patients who underwent 3-stage MIE between June 2006 and July 2012 were included. Of these, 178 patients were given preoperative milk orally 6 hours before surgery (Group M+), and 166 underwent MIE without preoperative milk and served as controls (Group M−). Patient demographics were retrospectively collected. The incidences of intraoperative thoracic duct identification and postoperative chylothorax were recorded and statistically compared between the 2 groups. Results: In this cohort, the 2 groups were comparable in clinical features including age, sex, tumor location, histologic type, and TNM stage. No patient was converted to open thoracotomy. During the thoracoscopic stage, a higher incidence of duct identification (95.5% vs 12.7%, p < 0.001) and a lower incidence of duct ligation (6.74% vs 13.25%, p = 0.039) were recorded in Group M+. Postoperatively, a total of 10 cases of chylothorax (2.91%) were observed. The incidence of chylothorax was significantly lower in Group M+ than in Group M− (0.56% vs 5.42%, p = 0.018). Conclusions: Preoperative oral administration of milk facilitates visualization of the thoracic duct and minimizes the risk of iatrogenic injury to the thoracic duct during thoracoscopic esophagectomy. It is a simple and safe method for preventing chyle leakage after MIE. A randomized and controlled trial is required to confirm these findings. [Copyright &y& Elsevier]

● GdB 6 is extremely stable under high pressure. ● Contrary to most other materials, the smooth X-ray diffraction rings of GdB 6 become spotty under high pressure. ● High-pressure spotty diffraction rings of GdB 6 are caused by the regional texture effect, which is reversible. ● Grain rotation behavior motivated by stress difference dominates the regional texturing in GdB 6. [Display omitted] As hard and refractory materials with high chemical resistance and mechanical strength, lanthanide hexaborides (LnB 6) have attracted much attention. Among the family of LnB 6 , gadolinium hexaboride (GdB 6) occupies a special position due to the half-filled 4 f shell of Gd. Here, using in situ synchrotron radiation angle-dispersive X-ray diffraction in a diamond anvil cell at room temperature, the structural stability and compression behavior of GdB 6 are investigated extensively, GdB 6 is observed to be structurally stable up to 73 GPa, and the bulk modulus of 177 GPa is obtained under hydrostatic compression. In this paper, an interesting observation of pressure-induced spotty diffraction rings of GdB 6 is reported, its formation mechanism can be well described by the reversible regional texture effect, which highlights the rearrangement of crystal grains under high pressure. The rearrangement mechanism has been well explained by investigating the pressure dependence of full width at half maximum, macro-differential stress and grain size. Collective grain rotation behavior motivated by stress difference is critical for the rearrangement process, the strong isotropy and strong stability of GdB 6 structure also provide necessary conditions for high-pressure grain rotation behavior. These results will help to promote the understanding of high-pressure structural properties of GdB 6 , and provide novel insights on the high-pressure grain behavior in hard materials with strong isotropy and three-dimensional skeleton constituted of strong covalent bonds. [ABSTRACT FROM AUTHOR]

Background: During the last few years, prone thoracoscopic esophagectomy has been increasingly adopted for thoracolaparoscopic esophagectomy (TLE). However, evidence for the prone position (PP) over the decubitus position (DP) during TLE is currently not strong enough to reach conclusions. Study Design: From May 2009 to December 2010, we conducted thoracoscopic esophagectomies in the DP and then PP on consecutive patients admitted to our institution. TLE in DP was conducted from May 2009 to February 2010 and in PP from March 2010 to December 2010. Clinical features and operation characteristics of all patients were collected and compared to determine differences between the 2 groups. Results: A total of 93 consecutive esophageal cancer patients were enrolled; Forty-one had their operations in DP and 52 in PP. There was no significant difference found between the 2 groups in age, sex, body mass index, tumor location, histological type, and TNM stage. When compared with DP, thoracoscopic esophagectomy in PP had a shorter operation duration (67 vs 77 minutes; p = 0.013), horter overall hospital stay (17.4 vs 11.4 days; p = 0.011), and yielded a larger number of lymph nodes (11.6 ± 4.0 vs 8.9 ± 4.9 on average; p = 0.005). Complication rates were similar between the 2 groups, with anastomotic leak developing in a significantly smaller number of patients in PP (7.7% vs 22.0%; p = 0.049). Conclusions: TLE in the PP is a feasible and safe alternative to DP and is potentially associated with fewer complications. Additional randomized studies are required to discuss the long-term prognostic value of this procedure. [Copyright &y& Elsevier]