Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer.From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed.A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I.Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I.
Enhanced recovery after surgery programs are safe and effective, and increased implementation is justified for perioperative care in colorectal surgery. Future studies may examine the benefits of enhanced recovery after surgery programs in elderly patients and in other GI surgery.
The conventional strategy for cancer gene therapy offers limited control of specificity and efficacy. A possible way to overcome these limitations is to construct logic circuits. Here we present modular AND gate circuits based on CRISPR-Cas9 system. The circuits integrate cellular information from two promoters as inputs and activate the output gene only when both inputs are active in the tested cell lines. Using the luciferase reporter as the output gene, we show that the circuit specifically detects bladder cancer cells and significantly enhances luciferase expression in comparison to the human telomerase reverse transcriptase-renilla luciferase construct. We also test the modularity of the design by replacing the output with other cellular functional genes including hBAX, p21 and E-cadherin. The circuits effectively inhibit bladder cancer cell growth, induce apoptosis and decrease cell motility by regulating the corresponding gene. This approach provides a synthetic biology platform for targeting and controlling bladder cancer cells in vitro.
Sarcopenia and previous abdominal surgery are independent risk factors for complications after surgery for colorectal cancer. Including a functional aspect to the definition of sarcopenia may result in a better prediction of postoperative complications.
The complex phenotypes of eukaryotic cells are controlled by decision-making circuits and signaling pathways. A key obstacle to implementing artificial connections in signaling networks has been the lack of synthetic devices for efficient sensing, processing and control of biological signals. By extending sgRNAs to include modified riboswitches that recognize specific signals, we can create CRISPR-Cas9-based 'signal conductors' that regulate transcription of endogenous genes in response to external or internal signals of interest. These devices can be used to construct all the basic types of Boolean logic gates that perform logical signal operations in mammalian cells without needing the layering of multiple genetic circuits. They can also be used to rewire cellular signaling events by constructing synthetic links that couple different signaling pathways. Moreover, this approach can be applied to redirect oncogenic signal transduction by controlling simultaneous bidirectional (ON-OFF) gene transcriptions, thus enabling reprogramming of the fate of cancer cells.
Background: The safety and effectiveness of early oral feeding after colorectal surgery has not been determined. We performed a meta-analysis to evaluate surgical outcomes following early oral feeding compared with traditional oral feeding in patients undergoing elective colorectal surgery. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials comparing the outcomes following early oral feeding versus traditional oral feeding in patients undergoing elective colorectal surgery. The trials must have reported at least one of the following end points: anastomotic dehiscence, pneumonia, wound infection, nasogastric tube reinsertion, vomiting, mortality, length of hospital stay, hospital costs, and quality of life. Results: Seven trials, which included a total of 587 patients, met our inclusion criteria. Compared with traditional oral feeding, early oral feeding reduced the length of hospital stay (weighted mean difference -1.58 days; 95% CI -2.77 to -0.39; p = 0.009) and the total postoperative complications (relative risk 0.70; 95% CI 0.50-0.98; p = 0.04). There were no significant differences in the risk of anastomotic dehiscence, pneumonia, wound infection, rate of nasogastric tube reinsertion, vomiting, or mortality. Conclusions: Early oral feeding is safe and effective in patients undergoing elective colorectal surgery.
The abundant and reversible N6‐methyladenosine (m6A) R
NA
modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated (
FTO
), as an m6A demethylase, plays a critical anti‐tumorigenic role in clear cell renal cell carcinoma (cc
RCC
).
FTO
is suppressed in cc
RCC
tissue. The low expression of
FTO
in human cc
RCC
correlates with increased tumour severity and poor patient survival. The Von Hippel‐Lindau‐deficient cells expressing
FTO
restores mitochondrial activity, induces oxidative stress and
ROS
production and shows impaired tumour growth, through increasing expression of
PGC
‐1α by reducing m6A levels in its
mRNA
transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical
FTO
‐
PGC
‐1α axis for developing effective therapeutic strategies in the treatment of cc
RCC
.
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