Methyltransferase-like 1 (METTL1) mediated 7-methylguanosine (m7G) is crucial for the regulation of chemoresistance in cancer treatment. However, the role of METTL1 in regulating chemoresistance of colon cancer (CC) cells to cisplatin is still unclear. This study established the cisplatin-resistant CC (CR-CC) cells and found that METTL1 was low-expressed in CR-CC cells compared to their paired cisplatin-sensitive CC (CS-CC) cells. Besides, overexpressed METTL1 enhanced the cytotoxic effects of cisplatin on CR-CC cells. In addition, miR-149-3p was the downstream target of METTL1, which could be positively regulated by METTL1. Further results validated that miR-149-3p was low-expressed in CR-CC cells comparing to the CS-CC cells. In addition, the promoting effects of overexpressed METTL1 on cisplatin induced CR-CC cell death were abrogated by synergistically knocking down miR-149-3p. Furthermore, S100A4/p53 axis was the downstream target of METTL1 and miR-149-3p, and either overexpressed METTL1 or miR-149-3p increased p53 protein levels in CR-CC cells, which were reversed by upregulating S100A4. Similarly, the promoting effects of overexpressed METTL1 on cisplatin-induced CR-CC cell death were abrogated by overexpressing S100A4. Taken together, overexpression of METTL1 sensitized CR-CC cells to cisplatin by modulating miR-149-3p/S100A4/p53 axis.

These data indicate potential associations between BTLA and PD-1 polymorphisms and CRC susceptibility. Additionally, the three co-inhibitory molecule gene SNPs have environmental interactions associated with CRC risk.

Background & ObjectiveNutrition assessment enables early identification of malnourished patients and those at risk of malnutrition. To determine the prevalence of malnutrition, to analyze the correlation between short-form Mini Nutritional Assessment (MNA-SF) and Nutritional Risk Screening 2002 (NRS2002) with classical nutritional markers among elderly hospitalized patients in surgery departments, with a view to improving nutrition advice for these patients.MethodsA total of 142 elderly patients admitted for surgery were enrolled in the study. Within 48 hours of admission, MNA-SF and NRS2002 scale, anthropometric measures and biochemical tests were carried out to assess the nutritional status of each patient.ResultsThe prevalence of malnutrition classified by MNA-SF, NRS2002, BMI, serum albumin, hemoglobin, total lymphocyte count, handgrip strength, calf circumference and mid-arm circumference were 45 %, 38 %, 17 %, 22 %, 24 %, 71 %, 36 %, 12 % and 15 %, respectively. As the nutritional status classified by both MNA-SF and NRS2002 deteriorated, BMI, serum albumin, hemoglobin, handgrip strength, mid-arm circumference and calf circumference of patients with malnutrition were lower (P < 0.05). MNA-SF and NRS2002 had a unanimous correlation with classical nutritional markers (P < 0.05) except total lymphocyte count (P > 0.05). MNA-SF results showed a moderate agreement (P < 0.001) with NRS2002. Malnourished patients were older than well-nourished patients with NRS2002 (P < 0.05). Digestive disease patients tend to suffer from malnutrition, evaluated by MNA-SF (P < 0.05).ConclusionsThe results show a relatively high prevalence of malnutrition among elderly patients in our general surgery department, especially in patients with digestive disease. NRS2002 and MNA-SF on elderly patients showed great consistency but significant difference in elderly patients with digestive disease. Both MNA-SF and NRS2002 correlated with each other and with BMI, serum albumin, hemoglobin, handgrip strength, calf circumference and mid-arm circumference. MNA-SF may be a more suitable tool for the nutrition assessment of surgical elderly inpatients.

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IMPORTANCEThe effect of and optimal timing for initiating supplemental parenteral nutrition (SPN) remain unclear after major abdominal surgery for patients in whom energy targets cannot be met by enteral nutrition (EN) alone.OBJECTIVE To examine the effect of early supplemental parenteral nutrition (E-SPN) (day 3 after surgery) or late supplemental parenteral nutrition (L-SPN) (day 8 after surgery) on the incidence of nosocomial infections in patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to EN. DESIGN, SETTING, AND PARTICIPANTSA multicenter randomized clinical trial was conducted from April 1, 2017, to December 31, 2018, in the general surgery department of 11 tertiary hospitals in China. Participants were those undergoing major abdominal surgery with high nutritional risk and poor tolerance to EN (Յ30% of energy targets from EN on postoperative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) and an expected postoperative hospital stay longer than 7 days. Data analysis was performed from February 1 to October 31, 2020.INTERVENTIONS Random allocation to E-SPN (starting on day 3 after surgery) or L-SPN (starting on day 8 after surgery). MAIN OUTCOMES AND MEASURESThe primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge.RESULTS A total of 230 patients (mean [SD] age, 60.1 [11.2] years; 140 men [61.1%]; all patients were of Han race and Asian ethnicity) were randomized (115 to the E-SPN group and 115 to the L-SPN group). One patient in the L-SPN group withdrew informed consent before the intervention. The E-SPN group received more mean (SD) energy delivery between days 3 and 7 compared with the L-SPN group (26.5 [7.4] vs 15.1 [4.8] kcal/kg daily; P < .001). The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (10/115 [8.7%] vs 21/114 [18.4%]; risk difference, 9.7%; 95% CI, 0.9%-18.5%; P = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (31/115 [27.0%] vs 38/114 [33.3%]; risk difference, 6.4%; 95% CI, −5.5% to 18.2%; P = .32), total adverse events (75/115 [65.2%] vs 82/114 [71.9%]; risk difference, 6.7%; 95% CI, −5.3% to 18.7%; P = .32), and rates of other secondary outcomes. A significant difference was found in the mean (SD) number of therapeutic antibiotic days between the E-SPN group and the L-SPN group (6.0 [0.8] vs 7.0 [1.1] days; mean difference, 1.0 days; 95% CI, 0.2-1.9 days; P = .01). CONCLUSION AND RELEVANCEIn this randomized clinical trial, E-SPN was associated with reduced nosocomial infections in patients undergoing abdominal surgery and seems to be a favorable strategy for patients with high nutritional risk and poor tolerance to EN after major abdominal surgery.