The unknown vibration has a significant negative effect on the elastic aircraft health. Therefore, it is necessary to predict the vibration response of the structure accurately. However, most ...existing methods have poor prediction effects when the target points exist operational force. To overcome this shortcoming, we propose a response prediction method based on the global transfer function (GTF). The GTF predicts the target responses directly using the reference responses, which neither requires operational force nor relies on the dynamics model. Further more, the contribution of the target point excitation can be effectively compensated and corrected. Experiments of finite element model and real-life systems is used to validate the effectiveness and accuracy of GTF. Effects of sensor location, number of sensors, excitation type, excitation application method and noise level are studied in detail. In addition, the GTF and response prediction results based on direct transfer function (DTF) are compared. The results show that the GTF could predict vibration response effectively and satisfy industrial requirements. Consequently, the GTF could be a promising computational method for response prediction of elastic aircraft.
The utility of cell-free nucleic acids in monitoring cancer has been recognized by both scientists and clinicians. In addition to human transcripts, a fraction of cell-free nucleic acids in human ...plasma were proven to be derived from microbes and reported to have relevance to cancer. To obtain a better understanding of plasma cell-free RNAs (cfRNAs) in cancer patients, we profiled cfRNAs in ~300 plasma samples of 5 cancer types (colorectal cancer, stomach cancer, liver cancer, lung cancer, and esophageal cancer) and healthy donors (HDs) with RNA-seq. Microbe-derived cfRNAs were consistently detected by different computational methods when potential contaminations were carefully filtered. Clinically relevant signals were identified from human and microbial reads, and enriched Kyoto Encyclopedia of Genes and Genomes pathways of downregulated human genes and higher prevalence torque teno viruses both suggest that a fraction of cancer patients were immunosuppressed. Our data support the diagnostic value of human and microbe-derived plasma cfRNAs for cancer detection, as an area under the ROC curve of approximately 0.9 for distinguishing cancer patients from HDs was achieved. Moreover, human and microbial cfRNAs both have cancer type specificity, and combining two types of features could distinguish tumors of five different primary locations with an average recall of 60.4%. Compared to using human features alone, adding microbial features improved the average recall by approximately 8%. In summary, this work provides evidence for the clinical relevance of human and microbe-derived plasma cfRNAs and their potential utilities in cancer detection as well as the determination of tumor sites.
It is generally accepted that colorectal cancer (CRC) originates from cancer stem cells (CSCs), which are responsible for CRC progression, metastasis and therapy resistance. The high heterogeneity of ...CSCs has precluded clinical application of CSC-targeting therapy. Here, we aimed to characterize the stemness landscapes and screen for certain patients more responsive to immunotherapy.
Twenty-six stem cell gene sets were acquired from StemChecker database. Consensus clustering algorithm was applied for stemness subtypes identification on 1,467 CRC samples from TCGA and GEO databases. The differences in prognosis, tumor microenvironment (TME) components, therapy responses were evaluated among subtypes. Then, the stemness-risk model was constructed by weighted gene correlation network analysis (WGCNA), Cox regression and random survival forest analyses, and the most important marker was experimentally verified.
Based on single-sample gene set enrichment analysis (ssGSEA) enrichments scores, CRC patients were classified into three subtypes (C1, C2 and C3). C3 subtype exhibited the worst prognosis, highest macrophages M0 and M2 infiltrations, immune and stromal scores, and minimum sensitivity to immunotherapies, but was more sensitive to drugs like Bosutinib, Docetaxel, Elesclomol, Gefitinib, Lenalidomide, Methotrexate and Sunitinib. The turquoise module was identified by WGCNA that it was most positively correlated with C3 but most negatively with C2, and five hub genes in turquoise module were identified for stemness model construction. CRC patients with higher stemness scores exhibited worse prognosis, more immunosuppressive components in TME and lower immunotherapeutic responses. Additionally, the model's immunotherapeutic prediction efficacy was further confirmed from two immunotherapy cohorts (anti-PD-L1 in IMvigor210 cohort and anti-PD-1 in GSE78220 cohort). Mechanistically, Gene Set Enrichment Analysis (GSEA) results revealed high stemness score group was enriched in interferon gamma response, interferon alpha response, P53 pathway, coagulation, apoptosis, KRAS signaling upregulation, complement, epithelial-mesenchymal transition (EMT) and IL6-mediated JAK-STAT signaling gene sets.
Our study characterized three stemness-related subtypes with distinct prognosis and TME patterns in CRC patients, and a 5-gene stemness-risk model was constructed by comprehensive bioinformatic analyses. We suggest our stemness model has prospective clinical implications for prognosis evaluation and might facilitate physicians selecting prospective responders for preferential use of current immune checkpoint inhibitors.
The purpose of our study was to compare the short-term outcomes of early (within 3 months after stroke) and nonearly (more than 3 months after stroke) radical colorectal cancer surgery to find an ...appropriate time to surgery for these colorectal cancer patients complicated with new-onset cerebral infarction. A retrospective analysis of patients with stroke who underwent curative colorectal cancer surgery between January 2010 and December 2020 was conducted. Propensity score matching (PSM) analysis was performed to overcome patient selection bias between the two groups. A total of 395 patients were reviewed. After PSM, 40 patients in the early group and 40 patients in the nonearly group were compared. The median time to surgery was 4 weeks in the early group. The overall incidence of postoperative complications between the groups was not significantly different (p = 0.745). The early group was associated with less intraoperative blood loss (50 vs. 100, p = 0.029 ml), with no difference in 30-day morbidity and mortality. Additionally, multivariate logistic regression analysis showed that previous abdominal surgery (p = 0.049) was an independent risk factor for postoperative complications after matching. Before matching, multivariate logistic analysis showed that ESRS (p = 0.028) and MRS (p = 0.039) were independent risk factors. Radical surgery after 4 weeks of cerebral infarction may be feasible for colorectal cancer patients with new onset stroke, as it appear not to increase the perioperative complications of Clavien-Dindo grade II or higher, while strengthening the preoperative evaluation and perioperative monitoring.
Luteolin, which is a natural flavonoid, has anti-inflammatory, antioxidant, and anticancer properties. Numerous studies have proven that luteolin inhibits the growth of many types of cancer cells by ...promoting apoptosis, autophagy, and cell cycle arrest in tumour cells. However,
in vivo
research on this topic has been limited. In addition, other studies have shown that luteolin exerts a good inhibitory effect on apoptosis-resistant cancer cells. While existing studies have not completely elucidated the mechanism underlying this phenomenon, we assume that luteolin, which is a natural compound that exerts its effects through various mechanisms, may have the potential to inhibit tumour growth. In our study, we proved that luteolin exerted a good inhibitory effect on the proliferation of colon cancer cells according to CCK8 and EdU fluorescence assays, and the same conclusion was drawn in animal experiments. In addition, we found that luteolin, which is an antioxidant, unexpectedly promoted oxidative stress as shown by measuring the levels of oxidative balance-related indicators, such as reactive oxygen species (ROS), SOD, H
2
O
2
and GSH. However, the decreased oxidation of luteolin-treated HT-29 cells after treatment with the active oxygen scavenger NAC did not reverse the inhibition of cell growth. However, the Caspase1 inhibitor VX765 did reverse the inhibition of cell growth. Western blotting analysis showed that luteolin treatment increased the expression of Caspase1, Gasdermin D and IL-1β, which are members of the pyroptosis signalling pathway, in colon cancer cells. We further intuitively observed NLRP3/Gasdermin D colocalization in luteolin-treated HT-29 cells and mouse tumour tissues by immunofluorescence. These results suggest that luteolin inhibits the proliferation of colon cancer cells through a novel pathway called pyroptosis. This study provides a new direction for the development of natural products that inhibit tumour growth by inducing pyroptosis.
Objective
The vascular anatomic variations of the right colon present a challenge for colorectal surgeons. However, there have been few detailed studies of the variations in the anterosuperior ...pancreaticoduodenal vein (ASPDV).
Methods
We studied consecutive patients with right colon cancer who underwent laparoscopic right hemicolectomy at Peking University First Hospital (N = 117) between January 2018 and June 2021.
Results
The variations in the ASPDV were classified as type I (n = 101, (86.3%)), defined as ASPDVs draining into the gastrocolic trunk of Henle (GCT); type II (n = 10, (8.5%)), defined as ASPDVs draining into the superior mesenteric vein (SMV); or type III, defined as ASPDVs draining into both the GCT and SMV. For type I, subtypes were defined according to the branching of the ASPDVs: subtype a, with one branch (n = 87, (86.1%)); subtype b, with two branches (n = 12, (11.9%)); and subtype c, with more than two branches (n = 2, (2.0%)). Type I was also subtyped according to the confluence of the ASPDV and GCT, with subtype 1 being defined by a proximal site (n = 96, 95%) and subtype 2 by a distal site (n = 5, 5.0%).
Conclusions
We have characterized the variations in ASPDVs encountered during laparoscopic right hemicolectomy, which should provide a reference for colorectal surgeons.
Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its ...antitumor role remains to be elucidated. The aim of this study is to explore the mechanisms underlying the tumor suppressive activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 eliminates colorectal cancer (CRC) cells by activating gasdermin D (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in turn promotes NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively inhibits the proliferation of CRC cells
and in nude mouse models. Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing great anticancer potential.
The majority of gastric cancer (GC) patients are in a progressive stage at the initial stage of treatment, and the overall response rate to immunotherapy remains unsatisfactory largely due to the ...lack of effective prognostic biomarkers. Immunogenic cell death (ICD) was identified as a new form of regulated cell death that can activate adaptive immune responses and further promote immunotherapy efficacy. Therefore, we attempted to characterize the ICD-associated signature to stratify patients who could benefit from immunotherapy. In our study, two subgroups of patients were identified based on the data of 34 ICD-related genes extracted from The Cancer Genome Atlas database via consensus clustering. The estimated scores, stromal scores, immune scores, tumor purity, and survival rate showed significant differences between the low and high ICD groups. Then, we constructed an ICD-related risk signature, including IFNB1, IL6, LY96, and NT5E, using least absolute shrinkage and selection operator Cox regression analysis; then, high- and low-risk groups could be clearly distinguished. Notably, the risk score is a reliable predictor of the prognosis and immunotherapy outcome in GC, which was further validated in an immunohistochemistry assay. These results suggest that ICD is closely associated with the prognosis and tumor immune microenvironment in GC. Taken together, this study first constructed and validated a prognostic ICD-related signature to predict the survival and effect of immunotherapy in GC, which provided new insight for potent individualized immunotherapy strategies.
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare variant of the inflammatory myofibroblastic tumor, characterized by more aggressive clinical course and nuclear membrane staining of ...anaplastic lymphoma kinase (ALK) with ALK rearrangement. An elderly male came to the clinic because of an accidental abdominal mass. Abdominal and pelvic enhanced CT revealed a tumor apparently orginated from mesenchymal tissue. Subsequently, the abdominal mass and multiple organ resection was performed, and the mass was pathologically confirmed as EIMS. The patient developed Clavien-Dindo Grade III postoperative complications and was discharged after his condition improved. He received doxorubicin monotherapy after operation, but only one cycle was administered due to severe vomiting. The follow-up of 5 months after operation showed no evidence of recurrence. Given the rarity of EIMS, and ALk inhibitors have a long and robust effect on patients with ALK gene tumors, it is very important for clinicians to be familiar with the clinicopathological features of EIMS, which will contribute to the accurate diagnosis of EIMS and reduce misdiagnosis.
There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the ...single-stage and two-stage strategies.
All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared.
Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes 31(27, 38) vs 17 (12, 24), P < 0.001, required less blood transfusion 0 (0, 100) vs 200 (0, 800), P = 0.034, had a shorter ICU stay 0 (0, 1.5) vs 3 (0, 3), P = 0.009, and had a significantly better OS (Median OS: 45 months vs 11 months, P = 0.007). Compared with propensity score-matched regular GC patients without perforation, PGC patients who underwent one-stage gastrectomy had a poorer quality of lymphadenectomy 17 (12, 24) vs 29 (21, 37), P < 0.001 and suffered a worse OS (Median OS: 18 months vs 30 months, P = 0.024). Conversely, two-stage gastrectomy can achieve a comparable quality of lymphadenectomy (P = 0.506) and a similar OS (P = 0.096) compared to propensity score-matched regular GC patients.
For PGC patients in poor condition, two-stage treatment is a better option when D2 radical gastrectomy cannot be achieved in emergency surgery, based on our findings that two-stage gastrectomy could provide PGC patients with a better quality of lymphadenectomy and a better OS.
