The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma / 中华肝脏病杂志

Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.

Safety and efficacy of therapeutic endoscopic retrograde cholangiopancreatography for elderly patients with biliary and pancreatic diseases based on enhanced recovery after surgery / 中国内镜杂志

Objective To study the safety and efficacy of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in elderly patients with biliary and pancreatic diseases under the concept of enhanced recovery after surgery (ERAS). Methods 320 patients were enrolled in ERCP operation. Both ERAS elderly group (experimental group A, n = 58, above 75 years) and young and middle-aged group (control group B, n=202,below 60 years)underwent enhanced recovery after surgery,meanwhile traditional elderly group(control group C, n = 60, above 75 years) received traditional perioperative management. It had compared multiple clinical indexes between group A with B and group A with C during the preoperative, intraoperative, and postoperative period. Results The incidence rate of cholangiocarcinoma, multiple complications, nutrition screening ≥ 3 points, ASA scored III degree and Child-Pugh scored A-level in preoperative ERAS elderly patients were higher than that of the young and middle-aged group (P < 0.05); And its incidence rate of nausea and vomiting and abdominal pain,nutritional screening < 3 points and ASA scored I degree were lower than that of the middle-aged group (P < 0.05);the fasting and water- deprivation time of the ERAS elderly group was shorter than that of the traditional elderly group (P < 0.05). The intraoperative operation time of the elderly ERAS group was slightly longer than that of the traditional elderly group (P < 0.05). The duration of electrocardiographic monitoring and the first aerofluxus time of the elderly patients with ERAS were longer than that of the young and middle-aged group (P < 0.05). The success, failure rate, and complication rate of the elderly patients with ERAS were 91.38% (53/58) and 8.62% (5 /58), 3.45% (2/58), meanwhile the young and middle-aged group were 96.53% (195/202), 3.47% (7/202), and 4.95% (10/202), and with no statistical difference (P > 0.05). The mild pain in ERAS elderly group was more than that of in traditional elderly group, while the moderate, and severe pain was less than that of traditional elderly group (P < 0.05); The opioid use rate, endoscopic nasobiliary indwelling, first-time ambulation and aerofluxus, total hospitalization, and postoperative hospitalization time of ERAS elderly group was less than the traditional elderly group (P < 0.05). Conclusions With ERAS, the treatment effect of ERCP in elderly patients is similar to that in young and middle-aged people, and it has good safety and effectiveness.