Composite nucleic acids, known as 2-5A antisense chimeras, cause the 2-5A-dependent ribonuclease (RNase L) to catalyze the specific cleavage of RNA in cell free systems and in intact cells. Such 2-5A antisense chimeras are 5'-monophosphorylated, 2,'5'-linked oligoadenylates covalently attached to antisense 3',5'-oligodeoxyribonucleotides by means of a linker containing two residues of 1,4-butanediol phosphate. Here we report a fully automated synthesis of 2-5A antisense chimeras on a solid support using phosphoramidite methodology with specific coupling time modifications and their subsequent purification by reverse-phase ion-pair and anion exchange HPLC. Purified 2-5A antisense chimeras were characterized by [1H]NMR and [31P]NMR, MALDIMS, and capillary gel electrophoresis. The synthetic 2',5'-linked oligoadenylate showed no phosphodiester isomerization to 3',5' during or after synthesis. In addition, we have developed facile methodologies to characterize the chimeras using digestion with various hydrolytic enzymes including snake venom phosphodiesterase I and nuclease P1. Finally, Maxam-Gilbert chemical sequencing protocols have been developed to confirm the entire sequence of these chimeric oligonucleotides.
Objective: Our objective is to validate the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) criteria in malnutrition diagnosis compared with Patient-Generated Subjective Global Assessment (PG-SGA) and assess the impact of malnutrition diagnosed using GLIM criteria on the clinical outcomes of patients with GC.
Methods:We retrospectively analyzed the data of 895 patients who underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Nutrition assessment was performed on all patients according to the GLIM criteria and PG-SGA.The κ statistic was used to evaluate the agreement between two methods. Multivariate logistic regression and Cox regression based on single-factor analysis were used to predict postoperative complications and overall survival rates.Results: Based on the GLIM criteria, 38.3% of the patients were diagnosed as malnourished, including 21.7% Stage I (moderate malnutrition) and 16.6% Stage II (severe malnutrition). GLIM criteria had a moderate agreement with PG-SGA (κ = 0.548).Patients in the Stage II malnutrition group had a higher incidence of complications, a longer postoperative length of stay, and higher hospitalization costs. Logistic regression showed that Stage II malnutrition was an independent risk predictor of postoperative complications (odds ratio, 3.28; 95% confidence interval [CI], 2.18-4.94). Furthermore, Cox regression analysis showed that both Stage I (hazard ratio [HR], 1.52; 95% CI, 1.11-2.07; P = .009) and Stage II (HR, 1.85; 95% CI, 1.34-2.53; P < .001) malnutrition were independent risk predictors of overall survival.
Conclusion:Diagnosis of malnutrition according to the GLIM criteria is useful in predicting the adverse postoperative clinical outcomes of patients with gastric cancer.
Sarcopenic obesity, together with age, open surgery, and combined resection are independent predictors of SPCs. Obesity will significantly increase the risk of SPCs in sarcopenic patient with gastric cancer, but it will not bring higher risk to normal patients. Our nomogram is a simple and practical instrument to identify patients at high risk of surgical complications.
PurposeSarcopenia is distinguished by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was designed to demonstrate the relationship between sarcopenia and systemic inflammatory response (neutrophil/lymphocyte ratio [NLR], platelet/lymphocyte ratio [PLR], and large platelet/lymphocyte ratio [LPLR]) prior to radical gastrectomy for gastric cancer.Patients and methodsWe conducted a prospective study of gastric cancer patients who underwent radical gastrectomy. The clinical utility of the NLR, PLR, and LPLR was evaluated by receiver operating characteristic curves. Sarcopenia components including skeletal muscle index, handgrip strength, and 6 m usual gait speed were measured. Logistic analysis was used to identify the independent indices associated with sarcopenia.ResultsA total of 670 patients were included, representing 504 men and 166 women. Of these, 104 patients (15.5%) were diagnosed with sarcopenia and 567 (84.5%) were non-sarcopenia. PLR has a diagnostic sensitivity of 91.3% for sarcopenia. In addition to the indicators of preoperative age, nutritional risk screening, body mass index, preoperative albumin, and diabetes, the NLR and PLR were independent predictors for sarcopenia (P<0.05).ConclusionThe present study showed that at-diagnosis sarcopenia was associated with inflammation in patients with operable gastric cancer. Due to the complex assessment of muscle condition, PLR may be used as a primary screening test for sarcopenia. How systemic inflammatory response influences changes in sarcopenia may provide new therapeutic perception toward improving outcomes.
The aims of the present study were to evaluate the predictive value of the platelet-to-lymphocyte ratio for peritoneal metastasis in patients with gastric cancer and to construct an available preoperative prediction system for peritoneal metastasis. A total of 1080 patients with gastric cancer were enrolled in our study. The preoperative platelet-to-lymphocyte ratio and other serum markers and objective clinical tumor characteristics were evaluated by receiver operating characteristic curves. A logistic analysis was performed to determine the independent predictive indicators of peritoneal metastasis. A prediction system that included the independent predictive indicators was constructed and evaluated by receiver operating characteristic curves. Based on the receiver operating characteristic curves, the ideal platelet-to-lymphocyte ratio cutoff value to predict peritoneal metastasis was 131.00. The logistic analysis showed that the platelet-to-lymphocyte ratio was an independent indicator to predict peritoneal metastasis. The area under the receiver operating characteristic curve was 0.599. When integrating all independent indicators (i.e., platelet-to-lymphocyte ratio, invasion depth, lymphatic invasion, pathological type), the prediction system more reliably predicted peritoneal metastasis with a higher area under the receiver operating characteristic curve (0.769). The preoperative platelet-to-lymphocyte ratio was an indicator that could be used to predict peritoneal metastasis. Our prediction system could be a reliable instrument to discriminate between patients with gastric cancer with and those without peritoneal metastasis.
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