The role of reactive oxygen species in gastric cancer.

Gastric cancer (GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species (ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC.

Plasma-Free Blood as a Potential Alternative to Whole Blood for Transcriptomic Analysis.

RNA sequencing (RNAseq) technology has become increasingly important in precision medicine and clinical diagnostics, and emerged as a powerful tool for identifying protein-coding genes, performing differential gene analysis, and inferring immune cell composition. Human peripheral blood samples are widely used for RNAseq, providing valuable insights into individual biomolecular information. Blood samples can be classified as whole blood (WB), plasma, serum, and remaining sediment samples, including plasma-free blood (PFB) and serum-free blood (SFB) samples that are generally considered less useful byproducts during the processes of plasma and serum separation, respectively. However, the feasibility of using PFB and SFB samples for transcriptome analysis remains unclear. In this study, we aimed to assess the suitability of employing PFB or SFB samples as an alternative RNA source in transcriptomic analysis. We performed a comparative analysis of WB, PFB, and SFB samples for different applications. Our results revealed that PFB samples exhibit greater similarity to WB samples than SFB samples in terms of protein-coding gene expression patterns, detection of differentially expressed genes, and immunological characterizations, suggesting that PFB can serve as a viable alternative to WB for transcriptomic analysis. Our study contributes to the optimization of blood sample utilization and the advancement of precision medicine research. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00121-1.

Needs and Constraints for Cardiac Rehabilitation Among Patients with Coronary Heart Disease Within a Community-Based Setting: A Study Based on Focus Group Interviews.

Objective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population. Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi's method of descriptive data analysis. Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) "Insufficient CR resources for patients": Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) "Patient CR initiative": Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise. Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.

Development and validation of a deep learning model for predicting gastric cancer recurrence based on CT Imaging: a multicenter study.

INTRODUCTION: The postoperative recurrence of gastric cancer has a significant impact on the overall prognosis of patients. Therefore, accurately predicting the postoperative recurrence of gastric cancer is crucial. METHODS: This retrospective study gathered data from 2,813 gastric cancer patients who underwent radical surgery between 2011 and 2017 at two medical centers. Follow-up was extended until May 2023, and cases were categorized as recurrent or non-recurrent based on postoperative outcomes. Clinical pathological information and imaging data were collected for all patients. A new deep learning signature (DLS) was generated using pretreatment CT images, based on a pre-trained baseline (a customized Resnet50), for predicting postoperative recurrence. The deep learning fusion signature (DLFS) was created by combining the score of DLS with the weighted values of identified clinical features. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. Survival curves were plotted to investigate the differences between DLFS and prognosis. RESULTS: In this study, 2813 patients with gastric cancer (GC) were recruited and allocated into training, internal validation, and external validation cohorts. The DLFS was developed and assessed for its capability in predicting the risk of postoperative recurrence. The DLFS exhibited excellent performance with AUCs of 0.833 (95% CI, 0.809-0.858) in the training set, 0.831 (95% CI, 0.792-0.871) in the internal validation set, and 0.859 (95% CI, 0.806-0.912) in the external validation set, along with satisfactory calibration across all cohorts (P>0.05). Furthermore, the DLFS model significantly outperformed both the clinical model and DLS (P<0.05). High-risk recurrent patients exhibit a significantly poorer prognosis compared to low-risk recurrent patients (P<0.05). CONCLUSIONS: The integrated model developed in this study, focusing on GC patients undergoing radical surgery, accurately identifies cases at high risk of postoperative recurrence and highlights the potential of DLFS as a prognostic factor for GC patients.

The Enhanced Performance of NiCuOOH/NiCu(OH)2 Electrode Using Pre-Conversion Treatment for the Electrochemical Oxidation of Ammonia.

Electrochemical oxidation of ammonia is an attractive process for wastewater treatment, hydrogen production, and ammonia fuel cells. However, the sluggish kinetics of the anode reaction has limited its applications, leading to a high demand for novel electrocatalysts. Herein, the electrode with the in situ growth of NiCu(OH)2 was partially transformed into the NiCuOOH phase by a pre-treatment using highly oxidative solutions. As revealed by SEM, XPS, and electrochemical analysis, such a strategy maintained the 3D structure, while inducing more active sites before the in situ generation of oxyhydroxide sites during the electrochemical reaction. The optimized NiCuOOH-1 sample exhibited the current density of 6.06 mA cm-2 at 0.5 V, which is 1.67 times higher than that of NiCu(OH)2 (3.63 mA cm-2). Moreover, the sample with a higher crystalline degree of the NiCuOOH phase exhibited lower performance, demonstrating the importance of a moderate treatment condition. In addition, the NiCuOOH-1 sample presented low selectivity (<20%) towards NO2- and stable activity during the long-term operation. The findings of this study would provide valuable insights into the development of transition metal electrocatalysts for ammonia oxidation.

Extend the benchmarking indel set by manual review using the individual cell line sequencing data from the Sequencing Quality Control 2 (SEQC2) project.

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

Pyrogenic Carbon Degradation by Galvanic Coupling with Sprayed Seawater Microdroplets.

Surface waves are known for their mechanical role in coastal processes that influence the weather and climate. However, their chemical impact, particularly on the transformation of pyrogenic carbon, is poorly understood. Pyrogenic carbon is generally assumed to show negligible postformational alteration of its stable carbon isotope composition. Here we present an electrochemical interaction of pyrogenic carbon with the sprayed seawater microdroplets resulting from wave breaking, driven by the galvanic coupling between the microdroplet water-carbon interfaces and the microdroplet water-vapor interfaces. This enables refractory pyrogenic carbon to rapidly degrade via the oxygenation and mineralization reaction, which makes it ∼2.6‰ enriched in 13C, far exceeding the generally assumed postformation alteration values (<0.5‰) of pyrogenic carbon. The unique chemical dynamics of seawater microdroplets provide new insights into the discrepancy in carbon isotope signatures between riverine and marine black carbon, emphasizing the potential of coastal oceans for carbon sequestration in the global carbon cycle.

The supplementation of Rothia as a potential preventive approach for bone loss in mice with ovariectomy-induced osteoporosis.

There is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of Rothia on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 µL/d) gavage of Rothia was performed for 8 weeks starting from 1 week after OVX. Microcomputed tomography was used to analyze the bone mass and bone microstructure of mice in each group after sacrifice. Histological staining and immunohistochemistry were then applied to identify the expression of pro-inflammatory cytokines, intestinal permeability, and osteogenic and osteoclastic activities of mice. The collected feces of mice in each group were used for 16S rRNA high-throughput sequencing to detect the alterations in composition, abundance, and diversity of gut microbiota. This study demonstrated that the gavage of Rothia alleviated bone loss in mice with OVX-induced osteoporosis, improved OVX-induced intestinal mucosal barrier injury, optimized intestinal permeability (zonula occludens protein 1 and occludin), reduced intestinal inflammation (tumor necrosis factor-α and interleukin-1ß), and regulated imbalance of gut microbiota. Based on "gut-bone" axis, this study revealed that regular and quantitative gavage of Rothia can relieve bone loss in mice with OVX-induced osteoporosis by repairing the intestinal mucosal barrier injury, optimizing the intestinal permeability, inhibiting the release of pro-inflammatory cytokines, and improving the disorder of gut microbiota.

Development and validation of nomogram for predicting early recurrence after radical gastrectomy of gastric cancer.

BACKGROUND: After radical surgery, early detection of recurrence and metastasis is a crucial factor in enhancing the prognosis and survival of patients with gastric cancer (GC). Therefore, assessing the risk of recurrence in gastric cancer patients and determining the timing for postoperative recurrence is crucial. METHODS: The clinicopathological data of 521 patients with recurrent gastric cancer, who underwent radical gastrectomy at Zhejiang Cancer Hospital between January 2010 and January 2017, were retrospectively analyzed. These patients were randomly divided into two groups: a training group (n = 365) and a validation group (n = 156). In the training set, patients were further categorized into early recurrence (n = 263) and late recurrence (n = 102) groups based on a 2-year boundary. Comparative analyses of clinicopathological features and prognoses were conducted between these two groups. Subsequently, a nomogram for predicting early recurrence was developed and validated. RESULTS: In this study, the developed nomogram incorporated age, serous infiltration, lymph node metastasis, recurrence mode, and the tumour marker CA19-9. In the training cohort, the area under the curve (AUC value) was 0.739 (95% CI, 0.682-0.798), with a corresponding C-index of 0.739. This nomogram was subsequently validated in an independent validation cohort, yielding an AUC of 0.743 (95% CI, 0.652-0.833) and a C-index of 0.743. Furthermore, independent risk factors for prognosis were identified, including age, absence of postoperative chemotherapy, early recurrence, lymph node metastasis, abdominal metastasis, and vascular cancer embolus. CONCLUSION: Independent risk factors for gastric cancer recurrence following radical surgery were utilized to construct a nomogram for predicting early relapse. This nomogram effectively assesses the risk of recurrence, aids in treatment decision-making and follow-up planning in clinical settings, and demonstrated strong performance in the validation cohort.

Ultrathin Metal-Organic Framework Nanosheets for Selective Photocatalytic C2 H2 Semihydrogenation in Aqueous Solution.

The selective semihydrogenation of C2 H2 to C2 H4 in crude C2 H4 (with ~1 vol % C2 H2 contamination) is a crucial process in the manufacture of polyethylene. Comparing to conventional thermalcatalytic route with Pd as catalyst under high temperature with H2 as hydrogen source, photocatalytic C2 H2 reduction reaction with H2 O as hydrogen source can achieve high selectivity under milder conditions, but has rarely been reported. Here, we present a kind of ultrathin metal-organic framework nanosheets (Cu-Co-MNSs) that demonstrate excellent catalytic activities in the semihydrogenation of C2 H2 . Employing Ru(bpy)3 2+ as the photosensitizer, this catalyst attains a noteworthy turnover number (TON) of 2124 for C2 H4 , coupled with an impressive selectivity of 99.5 % after 12 h visible light irradiation. This performance is comparable to molecular catalysts and notably surpasses the efficiency of bulk metal-organic framework materials. Furthermore, Cu-Co-MNSs achieve a 99.95 % conversion of C2 H2 under industrial relevant conditions (1.10 % C2 H2 in C2 H4 ) with 90.3 % selectivity for C2 H4 over C2 H6 , demonstrating a great potential for polymer-grade C2 H4 production.

The role of macrophages in gastric cancer.

As one of the deadliest cancers of the gastrointestinal tract, there has been limited improvement in long-term survival rates for gastric cancer (GC) in recent decades. The poor prognosis is attributed to difficulties in early detection, minimal opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are among the most abundant infiltrating immune cells in the GC stroma. These cells engage in crosstalk with cancer cells, adipocytes and other stromal cells to regulate metabolic, inflammatory and immune status, generating an immunosuppressive tumour microenvironment (TME) and ultimately promoting tumour initiation and progression. In this review, we summarise recent advances in our understanding of the origin of macrophages and their types and polarisation in cancer and provide an overview of the role of macrophages in GC carcinogenesis and development and their interaction with the GC immune microenvironment and flora. In addition, we explore the role of macrophages in preclinical and clinical trials on drug resistance and in treatment of GC to assess their potential therapeutic value in this disease.

TGFB1 induces fetal reprogramming and enhances intestinal regeneration.

The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy.

LINC01305 recruits basonuclin 1 to act on G-protein pathway suppressor 1 to promote esophageal squamous cell carcinoma.

EsophageaL squamous cell carcinoma (ESCC) is one of the most common and lethal tumors, however, its underlying molecular mechanisms are not completely understood and new therapeutic targets are needed. Here, we found that the transcription factor basonuclin 1 (BNC1) was significantly upregulated and closely related to the differentiation and metastasis of ESCC. Furthermore, BNC1, LINC01305, and G-protein pathway suppressor 1 (GPS1) had significant oncogenic roles in ESCC. In addition, in vivo experiments showed that knockdown of BNC1 indeed significantly inhibited the proliferation and metastasis of ESCC. We also revealed the molecular mechanism by which LINC01305 recruits BNC1 to the promoter of GPS1, and then GPS1 could mediate the JNK signaling pathway to promote the proliferation and metastases of ESCC. Taken together, we discovered the novel molecular mechanism by which LINC01305/BNC1 upregulates GPS1 expression to promote the development of ESCC, providing a new therapeutic target for ESCC.

Multi-omics data integration using ratio-based quantitative profiling with Quartet reference materials.

Characterization and integration of the genome, epigenome, transcriptome, proteome and metabolome of different datasets is difficult owing to a lack of ground truth. Here we develop and characterize suites of publicly available multi-omics reference materials of matched DNA, RNA, protein and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters. These references provide built-in truth defined by relationships among the family members and the information flow from DNA to RNA to protein. We demonstrate how using a ratio-based profiling approach that scales the absolute feature values of a study sample relative to those of a concurrently measured common reference sample produces reproducible and comparable data suitable for integration across batches, labs, platforms and omics types. Our study identifies reference-free 'absolute' feature quantification as the root cause of irreproducibility in multi-omics measurement and data integration and establishes the advantages of ratio-based multi-omics profiling with common reference materials.

Overexpression of CD99 is associated with tumor adaptiveness and indicates the tumor recurrence and therapeutic responses in gliomas.

Glioma undergoes adaptive changes, leading to poor prognosis and resistance to treatment. CD99 influences the migration and invasion of glioma cells and plays an oncogene role. However, whether CD99 can affect the adaptiveness of gliomas is still lacking in research, making its clinical value underestimated. Here, we enrolled our in-house and public multiomics datasets for bioinformatic analysis and conducted immunohistochemistry staining to investigate the role of CD99 in glioma adaptive response and its clinical implications. CD99 is expressed in more adaptative glioma subtypes and cell states. Under hypoxic conditions, CD99 is upregulated in glioma cells and is associated with angiogenesis and metabolic adaptations. Gliomas with over-expressed CD99 also increased the immunosuppressive tumor-associated macrophages. The relevance with tumor adaptiveness of CD99 presented clinical significance. We discovered that CD99 overexpression is associated with short-time recurrence and validated its prognostic value. Additionally, Glioma patients with high expression of CD99 were resistant to chemotherapy and radiotherapy. The CD99 expression was also related to anti-angiogenic and immune checkpoint inhibitor therapy response. Inhibitors of the PI3K-AKT pathway have therapeutic potential against CD99-overexpressing gliomas. Our study identified CD99 as a biomarker characterizing the adaptive response in glioma. Gliomas with high CD99 expression are highly tolerant to stress conditions such as hypoxia and antitumor immunity, making treatment responses dimmer and tumor progression. Therefore, for patients with CD99-overexpressing gliomas, tumor adaptiveness should be fully considered during treatment to avoid drug resistance, and closer clinical monitoring should be carried out to improve the prognosis.

Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study.

OBJECTIVE: Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead to high-performance blood tests towards GC diagnosis and prognosis. We attempted to develop diagnostic and prognostic models for GC based on plasma metabolic information. DESIGN: We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort and 264 participants in prospective cohort. Discovery and verification phases of diagnostic and prognostic models were conducted in retrospective cohort through machine learning and Cox regression of plasma metabolic fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, the developed diagnostic model was validated in prospective cohort by both NPELDI-MS and ultra-performance liquid chromatography-MS (UPLC-MS). RESULTS: We demonstrated the high throughput, desirable reproducibility and limited centre-specific effects of PMFs obtained through NPELDI-MS. In retrospective cohort, we achieved diagnostic performance with areas under curves (AUCs) of 0.862-0.988 in the discovery (n=1157 from 5 centres) and independent external verification dataset (n=787 from another 2 centres), through 5 different machine learning of PMFs, including neural network, ridge regression, lasso regression, support vector machine and random forest. Further, a metabolic panel consisting of 21 metabolites was constructed and identified for GC diagnosis with AUCs of 0.921-0.971 and 0.907-0.940 in the discovery and verification dataset, respectively. In the prospective study (n=264 from lead centre), both NPELDI-MS and UPLC-MS were applied to detect and validate the metabolic panel, and the diagnostic AUCs were 0.855-0.918 and 0.856-0.916, respectively. Moreover, we constructed a prognosis scoring system for GC in retrospective cohort, which can effectively predict the survival of GC patients. CONCLUSION: We developed and validated diagnostic and prognostic models for GC, which also contribute to advanced metabolic analysis towards diseases, including but not limited to GC.

The Preventive Effects of Probiotic Prevotella histicola on the Bone Loss of Mice with Ovariectomy-Mediated Osteoporosis.

It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this study is to investigate whether the supplementation of Prevotella histicola (Ph) can prevent the bone loss in mice with ovariectomy (OVX)-mediated OP, and further explore relevant mechanisms. Regular (once a day for 8 consecutive weeks) and quantitative (200 µL/d) perfusion of Ph (the bacteria that orally gavaged) was conducted starting from 1 week after the construction of mice models. Bone mass and bone microstructure were detected by Micro-computed tomography (Micro-CT). Expressions of intestinal permeability, pro-inflammatory cytokines, and osteogenic and osteoclastic activities of mice were analyzed by histological staining and immunohistochemistry (IHC). 16S rRNA high throughput sequencing technique was applied to analyze the alterations of composition, abundance, and diversity of collected feces. Regular and quantitative perfusion of Ph mitigated the bone loss in mice with OVX-mediated OP. Compared with OVX + PBS group, perfusion of Ph repressed osteoclastogenesis and promoted osteogenesis, reduced release of pro-inflammatory cytokine cytokines (interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)), and reversed expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin). Besides, the perfusion of Ph improved the composition, abundance, and diversity of GM. Collectively, this study revealed that regular and quantitative perfusion of Ph can improve the bone loss in mice with OVX-mediated OP by repairing intestinal mucosal barrier damage, optimizing intestinal permeability, inhibiting release of pro-osteoclastogenic cytokines, and improving disturbance of GM.

Prognostic significance of inflammatory and nutritional markers in perioperative period for patients with advanced gastric cancer.

BACKGROUND: It has been reported that inflammatory and nutritional markers are related to prognosis in numerous malignancies. The present study analyzed the significance of these markers' alterations during neoadjuvant chemotherapy in the long-term outcomes in patients with advanced gastric cancer. METHODS: A retrospective review was performed of 437 advanced gastric cancer patients who underwent a neoadjuvant chemotherapy (NACT) regimen followed by surgical treatment. Inflammatory and nutritional markers measured from the blood samples collected from the patients before the first neoadjuvant chemotherapy and after the last neoadjuvant chemotherapy were used for analysis. Statistical analysis, including Mann-Whitney U or chi-square tests, the Kaplan-Meier method and Cox multivariate analysis, were performed to analyze the predictive value of these markers for overall survival outcomes (OS). RESULTS: Most biomarkers, including lymphocyte, leucocyte, neutrophil, monocyte, platelet, LMR, PLR, SII, CRP, CAR, hemoglobulin and albumin levels, changed during NACT (P <  0.05). After separately grouping the patients based on the normal range of hematologic indexes and the change rate (α) of systemic inflammatory and nutritional markers by the cutoff value derived from X-tile (P <  0.05), we found that differentiation, TRG, pre-NACT BMI, pre-NACT platelet counts, post-NACT lymphocyte counts, the change in lymphocyte counts, change in platelet counts and LMR(α), PLR(α), SII(α), and CAR(α) were associated with OS. Multivariate analysis revealed that PLR (α) > - 19% was correlated with a 3.193-fold (95% CI: 2.194-4.649) higher risk of death (P <  0.001) than others. CONCLUSION: NACT could significantly change several inflammatory and nutritional markers in the perioperative period; the platelet counts before NACT, and the change in lymphocytes during NACT truly correlated with long-term outcomes among patients with advanced gastric cancer. The systemic inflammatory marker PLR may be a reliable marker for the prediction of prognosis.

hsa_circ_0140180 affects the migration and invasion of esophageal squamous cell carcinoma cells by regulating miR-1287-5p / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨hsa_circ_0140180在食管鳞状细胞癌（ESCC）细胞中的表达水平及对其细胞恶性生物学行为的影响与分子机制。方法：收集2018年11月至2019年3月间在南充市中心医院胸心外科手术切除的6对ESCC组织和对应癌旁组织并进行全转录组测序，筛选出在ESCC组织中低表达的hsa_circ_0140180；建立过表达hsa_circ_0140180的TE-1和KYSE30细胞，qPCR法检测hsa_circ_0140180在人正常食管上皮细胞、ESCC细胞中的表达，以及过表达hsa_circ_0140180后TE-1和KYSE30细胞中miR-1287-5p的表达；CCK-8法和FCM检测过表达hsa_circ_0140180对TE-1和KYSE30细胞增殖和周期的影响；划痕实验和Transwell实验检测过表达hsa_circ_0140180对TE-1和KYSE30细胞迁移和侵袭能力的影响，双荧光素酶报告实验验证hsa_circ_0140180与miR-1287-5p的靶向关系。WB法检测过表达hsa_circ_0140180对TE-1和KYSE30细胞中EMT相关蛋白的表达及PI3K-Akt通路的磷酸化水平的影响。结果：转录组测序和qPCR结果显示，hsa_circ_0140180在ESCC组织和细胞中呈低表达（P<0.05或P<0.01），并确认其闭合环状分子特征且定位于细胞质。过表达hsa_circ_0140180能明显抑制ESCC细胞的迁移及侵袭能力（P<0.05），但不影响其增殖和周期。双荧光素酶报告基因实验证实hsa_circ_0140180靶向结合miR-1287-5并负调控其表达（P<0.01）。过表达hsa_circ_0140180能显著上调TE-1和KYSE30细胞中E-cadherin的表达（（P<0.05），而显著下调Snail的表达（P<0.05）和PI3K-Akt通路的磷酸化水平（P<0.01或P<0.001）。结论：hsa_circ_0140180在ESCC细胞及组织中呈低表达，其可能通过调控miR-1287-5p表达来降低PI3K-Akt通路的磷酸化水平和抑制EMT进程，从而影响ESCC细胞的迁移及侵袭能力。