ObjectiveTo describe the research status of programmed death receptor protein 1 (PD-1) and its ligand(PD-L1) inhibitors in advanced gastric cancer and to understand the key issues of PD/PD-L1 inhibitors in order to provide atheoretical basis for future research.MethodThe classical and up to date literatures on the immunotherapy, especially thePD-1/PD-L1 inhibitors in the advanced gastric cancer were reviewed.ResultsThe PD-1/PD-L1 inhibitors were the hot spot in the current research of tumor immunotherapy. The pembrolizumab and nivolumab were the commonly immunosuppressive agents in the current clinical research, which had also achieved the great success in the clinical research of gastriccancer since it was shown the good results in the malignant melanoma and hematological malignancies. In some clinical studies, the PD-1/PD-L1 inhibitors treatment showed the longer overall survival than the conventional chemotherapy, especially in the patient with positive PD-1. However the study still had some issues to be solved, such as no accurate prediction for the beneficiary population, the tumor hyperprogression and so on. It was gratifying that the current research on the basic research of tumor immunity was increasing, then it provided a theoretical support for solving these problems.ConclusionsTumor immunosuppressive therapy such as PD-1/PD-L1 inhibitors brings a new idea in treatment of patients with advanced gastric cancer. Although there are still many problems need to be solved in clinical research, it is believed that PD-1/PD-L1 inhibitors will become one of key players in treatment of patients with advanced gastric cancer in the further study.
ObjectiveTo summarize the mechanism of hydrogen sulfide (H2S) in regulating autophagy and ameliorating multi-organ dysfunction in the treatment of sepsis.MethodThe relevant literatures at home and abroad in recent years were systematically searched and read to review the mechanism of H2S in regulating autophagy and ameliorating multi-organ dysfunction during sepsis.ResultsAs a new medical gas signal molecule, H2S could regulate autophagy by regulating multiple signal pathways such as Nrf2, NF-κB, MAPK, AMPK, etc., then ameliorated multi-organ dysfunction in sepsis.ConclusionH2S inhibits inflammation, oxidative stress, and apoptosis by regulating autophagy, thus ameliorating multi-organ dysfunction in sepsis, which is expected to become an effective therapeutic target for sepsis.
Objective To evaluate the efficacy and safety of intraoperative mesenchymal chemotherapy with 5-FU implants in radical gastrectomy of advanced gastric cancer. Methods From January 2008 to September 2009， 102 patients with historically proven advanced gastric cancer were enrolled in our department and were allocated to undergo either radical gastrectomy and intraoperative mesenchymal chemotherapy with 5-FU implants 800 mg（treatment group， n=51）， or radical gastrectomy alone （control group， n=51）. The postoperative complications and recurrence rate between two groups were compared. Results There were no significant differences on the volume of abdominal cavity drainage， count of white blood cells， albumin level， and gastrointestinal adverse events between the two groups （P＞0.05）. After a median follow-up of 28 months， the local recurrence rate was lower among patients in treatment group than that in control group （16.3% vs. 39.1%， P＜0.05）， the survival rate of 3-year was higher in treatment group than that in control group （85.8% vs. 67.3%， P＜0.05）. Conclusions Compared with the control group， there are no significant adverse reactions on patients with advanced gastric cancer who were implanted fluorouraci1 implants during operation， which can reduce local recurrence rates and improve the survival rates.
Objective To explore the influences of hydrogen sulfide （H2S） on acute necrotizing pancreatitis （ANP）. Methods Forty-three SD male rats were grouped by random number table， and divided into five groups：the sham group （n=4）， ANP group 〔n=21， which was divided into 3 subgroups：3， 6， and 12 hours group （n=7）〕， NaCl＋ANP group （n=4）， NaHS＋ANP group （n=7）， and PAG＋ANP group （n=7）. Models of ANP were formed byretrograde cholangiopancreatography injection of 5% sodium taurocholate. The NaCl＋ANP group， NaHS＋ANP group， and PAG＋ANP group rats were given pretreatment of saline， NaHS， or PAG at 1 hour before modelingrespectively. The levels of serum amylase （AMY）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， blood urea nitrogen （BUN）， and creatinine （Cr） were detected， and the pathological histological changes of pancreatic tissues were observed. Results The levels of serum AMY， AST， ALT， BUN， and Cr were increased in ANP group. The levels of serum AMY， AST， ALT， BUN， and Cr in the NaHS＋ANP group were higher than those of NaCl＋ANP group （P＜0.05）， and the pathological damage of the pancreatic tissues was more serious in the NaHS＋ANP group. The levels of serum AMY， AST， ALT， BUN， and Cr in the PAG＋ANP group were lower than those of NaCl＋ANPgroup （P＜0.05）， and the pathological damage of pancreatic tissues in the PAG＋ANP group was not so serious as in the NaCl＋ANP group. Conclusions The impairment of liver， kidney， and pancreas function in ANP rats may be related to elevated H2S concentration. Prophylactic administration the PAG of H2S antagonist can improve the function of the liver， kidney， and pancreas， and have the effects of organ protection.
ObjectiveTo investigate the potential role and mechanism of hydrogen sulfide (H2S) in regulating arterial baroreflex (ABR) in septic rats. MethodsThe rat model of cecal ligation and puncture (CLP) induced sepsis was established. Fortyseven male SpargueDawley rats were randomly divided into 9 groups: ① Sham operation (SO)+0.9% NaCl (NS) intravenous injection (i.v.) group; ② SO+NaHS i.v. group; ③ CLP+NaHS i.v. group; ④ SO+artificial cerebrospinal fluid (aCSF) bilater nucleus tractus solitarii (NTS) microinjection group; ⑤ SO+NaHS bilater NTS microinjection group; ⑥ SO+vehicle (DMSO)+NaHS group; ⑦ SO+Gli+NaHS group; ⑧ CLP+vehicle (DMSO) group; ⑨ CLP+Gli group. The ABR function was measured before administration and 5 min and 30 min after administration. Results① The ABR value of rats at different time in the same group: Compared with the ABR value before administration in the SO+NaHS i.v. group, CLP+NaHS i.v. group, SO+NaHS bilater NTS microinjection group, and SO+vehicle+NaHS group, the ABR values of rats significantly decreased at 5 min and 30 min after administration (Plt;0.05, Plt;0.01), which significantly increased in the CLP+Gli group at 5 min and 30 min after administration (Plt;0.05). ② The ABR value of rats at the same time in the different groups: Before administration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v.group (Plt;0.05). At 5 min and 30 min after adminis tration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v. group (Plt;0.05), which in the SO+NaHS i.v. group or SO+NaHS bilater NTS microinjection group was significantly lower than that in the SO+NS i.v. group or SO+aCSF bilater NTS microinjection group, respectively (Plt;0.05, Plt;0.01), in the SO+Gli+NaHS group or CLP+Gli group was significantly higher than that in the SO+vehicle+NaHS group or CLP+vehicle group, respectively (Plt;0.05). ConclusionsH2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the downregulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.
ObjectiveTo summarize the anti-inflammatory effects of irisin in inflammatory diseases.MethodThe relevant literatures at home and abroad in recent years were systematically searched and read to review the anti-inflammatory effects of irisin in the inflammatory diseases.ResultsThe irisin was widely distributed in the body and played a physiological role in inducing the browning of white adipocytes, improving energy metabolism and glucose utilization. A grow body of evidences demonstrated that the irisin exerted the anti-inflammatory effects by inhibiting increased pro-inflammatory cytokines and tumor necrosis factor-α, antagonizing apoptosis and activation of nuclear factor-κB, and improving tissue damage in many inflammatory diseases, such as acute lung injury, inflammatory bowel disease, septic cardiomyopathy, acute pancreatitis, nonalcoholic fatty liver disease, and malignant tumors.ConclusionsIrisin plays an important anti-inflammatory role in pathogenesis of inflammatory diseases. Irisin is considered as a promising candidate biomarker for diagnosis and prognosis of inflammatory diseases, and a novel target for treatment of inflammatory diseases.