Development of lactate-related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate-related genes (LRGs) in CRC patients remain to be elucidated. METHODS: We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated. RESULTS: We constructed lactate-related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance. CONCLUSION: We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.

Comparison of Clinical Efficacy and Safety Between da Vinci Robotic and Laparoscopic Intersphincteric Resection for Low Rectal Cancer: A Meta-Analysis.

Background and Aims: The intersphincteric resection (ISR) is beneficial for saving patients' anus to a large extent and restoring original bowel continuity. Laparoscopic ISR (L-ISR) has its drawbacks, such as two-dimensional images, low motion flexibility, and unstable lens. Recently, da Vinci robotic ISR (R-ISR) is increasingly used worldwide. The purpose of this article is to compare the feasibility, safety, oncological outcomes, and clinical efficacy of R-ISR vs. L-ISR for low rectal cancer. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to identify comparative studies of R-ISR vs. L-ISR. Demographic, clinical, and outcome data were extracted. Mean difference (MD) and risk ratio (RR) with their corresponding confidence intervals (CIs) were calculated. Results: Five studies were included. In total, 510 patients were included, of whom 273 underwent R-ISR and 237 L-ISR. Compared with L-ISR, R-ISR has significantly lower estimated intraoperative blood loss (MD = -23.31, 95% CI [-41.98, -4.64], P = 0.01), longer operative time (MD = 51.77, 95% CI [25.68, 77.86], P = 0.0001), hospitalization days (MD = -1.52, 95% CI [-2.10, 0.94], P < 0.00001), and postoperative urinary complications (RR = 0.36, 95% CI [0.16, 0.82], P = 0.02). Conclusions: The potential benefits of R-ISR are considered as a safe and feasible alternative choice for the treatment of low rectal tumors.

A system hierarchy for brain-inspired computing.

Neuromorphic computing draws inspiration from the brain to provide computing technology and architecture with the potential to drive the next wave of computer engineering1-13. Such brain-inspired computing also provides a promising platform for the development of artificial general intelligence14,15. However, unlike conventional computing systems, which have a well established computer hierarchy built around the concept of Turing completeness and the von Neumann architecture16-18, there is currently no generalized system hierarchy or understanding of completeness for brain-inspired computing. This affects the compatibility between software and hardware, impairing the programming flexibility and development productivity of brain-inspired computing. Here we propose 'neuromorphic completeness', which relaxes the requirement for hardware completeness, and a corresponding system hierarchy, which consists of a Turing-complete software-abstraction model and a versatile abstract neuromorphic architecture. Using this hierarchy, various programs can be described as uniform representations and transformed into the equivalent executable on any neuromorphic complete hardware-that is, it ensures programming-language portability, hardware completeness and compilation feasibility. We implement toolchain software to support the execution of different types of program on various typical hardware platforms, demonstrating the advantage of our system hierarchy, including a new system-design dimension introduced by the neuromorphic completeness. We expect that our study will enable efficient and compatible progress in all aspects of brain-inspired computing systems, facilitating the development of various applications, including artificial general intelligence.

Protease-activated receptor-2 induces expression of vascular endothelial growth factor and cyclooxygenase-2 via the mitogen-activated protein kinase pathway in gastric cancer cells.

Protease-activated receptor-2 (PAR-2) has shown strong pro-angiogenesis activity physiologically and pathologically. This study aimed to explore PAR-2 regulation of pro-angiogenesis gene expression and the underlying molecular pathways in gastric cancer cells. MKN28 human gastric cancer cells were treated with trypsin, a PAR-2 activator, and subjected to real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting and ELISA for gene expression analyses. ERK1/2 phosphorylation and p38 MAP kinase inhibitors (PD98059 and SB203580, respectively) were used to block their gene activities. PAR-2 mRNA and protein were expressed in MKN-28 cells and activated by trypsin treatment. Trypsin-activated PAR-2 protein significantly enhanced expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) mRNA and protein in gastric cancer cells in a dose- and time-dependent manner. PAR-2 activation also induced the phosphorylation of ERK1/2 and p38 MAP kinase, but the ERK1/2 and p38 inhibitors blocked the activated PAR-2-induced VEGF and COX-2 expression in gastric cancer cells. PAR-2-induced expression of VEGF and COX-2 mRNA and protein in gastric cancer MKN28 cells was mediated by activation of an ERK1/2- and p38 MAP kinase-dependent pathway. Thus, PAR-2 may serve as a promising target for anti-angiogenesis therapy to treat gastric cancer.

Effects of environmental hypothermia on hemodynamics and oxygen dynamics in a conscious swine model of hemorrhagic shock.

BACKGROUND: Hypothermia is associated with poor outcome in trauma patients; however, hemorrhagic shock (HS) model with anesthetized swine was different from that of clinical reality. To identify the effects of environmental hypothermia on HS, we investigated hemodynamics and oxygen dynamics in an unanesthetized swine model of HS under simulating hypothermia environment. METHODS: Totally 16 Bama pigs were randomly divided into ambient temperature group (group A) and low temperature group (group B), 8 pigs in each group. Venous blood (30 mL/kg) was continuously withdrawn for more than 15 minutes in conscious swine to establish a hemorrhagic shock model. Pulmonary arterial temperature (Tp), heart rate (HR), mean arterial pressure (MAP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), central venous pressure (CVP), cardiac output (CO), hemoglobin (Hb), saturation of mixed venous blood (SvO2) and blood gas analysis were recorded at the baseline and different hemorrhagic shock time (HST). The whole body oxygen delivery indices, DO2I and VO2I, and the O2 extraction ratio (O2ER) were calculated. RESULTS: Core body temperature in group A decreased slightly after the hemorrhagic shock model was established, and environmental hypothermia decreased in core body temperature. The mortality rate was significantly higher in group B (50%) than in group A (0%). DO2I and VO2I decreased significantly after hemorrhage. No difference was found in hemodynamics, DO2I and VO2I between group A and group B, but the difference in pH, lactic acid and O2ER was significant between the two groups. CONCLUSION: Environmental hypothermia aggravated the disorder of oxygen metabolism after hemorrhagic shock, which was associated with poor prognosis.