Inhibition of B7-H4 promotes hepatocellular carcinoma cell apoptosis and autophagy through the PI3K signaling pathway.

B7-H4 and autophagy can regulate or be induced by the PI3K signaling pathway. However, the association between B7-H4 and autophagy in hepatocellular carcinoma (HCC)remains unclear. The aim of this work was to investigate whether B7-H4 regulates autophagy via the PI3K signaling pathway in HCC cells. Here, western blotting was used to measure the expression of the related proteins involved in changes in of autophagy and apoptosis, such as LC3, P62, cleaved caspase 3, cleaved PARP, BCL-2, and BAX in Huh7 and Hep3B cells. Additionally, PI3K/AKT/mTOR signaling pathway proteins were measured. Cell counting kit-8 and flow cytometry were used to analyze the effects of B7-H4 siRNA interference on cell proliferation with the interference of B7-H4 siRNA. We found that B7-H4 siRNA increased HCC cell apoptosis and autophagy, and reduced cell proliferation. Moreover, the apoptosis-related proteins cleaved caspase 3, cleaved PARP and BAX were increased and Bcl-2 was decreased after B7-H4 siRNA interference. The expression level of the autophagy-related protein LC3Ⅱ was upregulated, while expression of the autophagy adaptor P62 expression was decreased in B7-H4 siRNA-pretreated cells. Furthermore, our data revealed that B7-H4 regulated apoptosis and autophagy through the PI3K signaling pathway in HCC cells. Therefore, these results suggested that B7-H4 plays an important role in HCC progression by affecting cell apoptosis and autophagy.

Unexpected Gallbladder Cancer during or after Laparoscopic Cholecystectomy: Risk Factors and Experience of Diagnosis and Treatment of 22 Cases.

This study aims to provide some experience in diagnosis and treatment of unexpected gallbladder cancer (UGBC) and find the major risk factors. Retrospective data were collected and analyzed on 22 patients who were diagnosed with UGBC during or after laparoscopic cholecystectomy from January 2013 to January 2018 at our hospital. Average age of the patients was (60.2 ± 12.8) years (range, 42-83 years). Among them, there were 6 men and 16 women. Gallbladder stones, atrophic gallbladder, uneven thickened wall of the gallbladder, and choledocholithiasis were found to be the major risk factors. Eight patients (36.4%) were diagnosed intraoperatively. Seven cases (31.8%) were at the T1 stage; of these, three were treated with laparoscopic cholecystectomy; two were converted to cholecystectomy; and two underwent cholecystectomy, lymph node dissection, and liver resection. Eight (36.4%) T2 patients, five (22.7%) T3 patients, and one T4 patient had radical cholecystectomy. Partial cholecystectomy and cholecystotomy were carried out in another T4 patient. T1 patients did not receive chemotherapy or radiotherapy. Eleven had chemotherapy and four received chemoradiotherapy. The follow-up period ranged from six months to five years. The one-year survival rate for T1 to T4 patients was 100 per cent, 75 per cent, 40 per cent, and 0 per cent, respectively. A high index of clinical suspicion of UGBC is needed if one patient suffered from both gallbladder stones and choledocholithiasis with atrophic gallbladder or uneven thickened wall of the gallbladder preoperatively. To avoid more UGBC and reoperation, imaging examinations combined with tumor marker tests and intraoperative histopathologic examination are highly recommended.