OBJECTIVETo systematically evaluate the efficacy and safety of surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced gastric cancer (AGC).

METHODSClinical control trials about the efficacy and safety of surgery combined with HIPEC in the treatment of advanced gastric cancer published before June 2014 were searched in Embase, PubMed, Cochrane Library, Wanfang database and CNKI database. Quality of enrolled articles was evaluated with the guidelines from Cochrane collaborative network. All the retrieved data were analyzed by RevMan 5.3 software for meta-analysis. Sensitivity analysis was performed by exclusion of non-randomly clinical control trials. Publication bias was evaluated by failure safe number (Nfs0.05).

RESULTSOf the 1489 AGC cases included from 16 literature, 698 underwent surgery with HIPEC (HIPEC group) while 791 underwent surgery alone (control group). According to whether or not the patient presented macroscopic peritoneal metastasis before the surgery, the HIPEC group was further divided into the curative HIPEC (n=102) and prophylactic HIPEC groups (n=421). The results of meta-analysis showed that, compared with control group, the 1-year (OR=2.26, 95%CI:1.71 ~ 3.00, P=0.000), 3-year (OR=2.27, 95%CI:1.80 - 2.87, P=0.000) and 5-year (OR=1.58, 95%CI:1.20 - 2.07, P=0.001) survival rates of HIPEC group were significantly improved with significantly decreased overall recurrence rate of liver, lung, bone or peritoneal metastasis (OR=0.43, 95%CI:0.26 - 0.71, P=0.001) and lower peritoneal metastasis recurrence rate (OR=0.30, 95%CI:0.17 - 0.52, P=0.000). However, there was higher incidence of procedure-related morbidity in the HIPEC group (OR=1.67, 95%CI:1.13 - 2.45, P=0.009), whereby the incidences of myelotoxicity (OR=4.90, 95%CI:1.05 - 22.83, P=0.040) and renal insufficiency were higher (OR=3.59, 95%CI:1.67 - 7.74, P=0.001). While the other complications, such as anastomotic leakage, intestinal obstruction and respiratory diseases were not significantly different between the two groups(all P>0.05). Subgroup analysis showed that compared with control group, the rates of peritoneal recurrence and metastasis in the prophylactic HIPEC group were significantly lower (OR=0.34, 95%CI:0.24 - 0.48, P=0.000), while such rates were not significantly different in curative HIPEC group (OR=0.07, 95%CI:0.00 - 1.88, P=0.110).

CONCLUSIONSSurgery combined with HIPEC can improve survival of AGC patients and reduce the recurrence rate after surgery. However its safety should be improved in the future.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate