ABSTRACT
Aim: To evaluate the clinical efficacy and safety of Xiaoaiping injection combined with chemotherapy in the treatment of advanced gastric cancer by meta-analysis. Methods: Seven databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, Cochrane Library, PubMed, Embase, and Web of Science, were searched by computer for randomized controlled clinical trials of Xiaoaiping injection combined with chemotherapy in the treatment of gastric cancer. Risk of bias assessment and meta-analysis were performed by Review Manager 5.3 software. Results: There were 16 articles that met the inclusion criteria, with a total of 1,236 patients, 617 in the observation group and 619 in the control group. The results of meta-analysis showed that the observation group was better than chemotherapy alone control group in RR [OR = 1.86, p < 0.00001]; disease control rate (DCR) [OR = 2.45, p < 0.00001]; Karnofsky performance status (KPS) score [OR = 3.21, p < 0.00001] or [MD = 7.73, p = 0.001]. In terms of biochemical indicators, Xiaoaiping significantly reduced inflammation factors level, including tumor necrosis factor alpha (TNF-α) [MD = -15.00, p < 0.00001]; interleukin-6 (IL-6) [MD = -13.00, p < 0.00001]; C-reaction protein (CRP) [MD = -5.80, p < 0.00001]. Xiaoaiping could enhance immune function, significantly reducing myeloid-derived suppressor cells (MDSCs) [MD = -6.20, p < 0.00001] and Treg [MD = -1.70, p < 0.00001]. Xiaoaiping injection combined with chemotherapy could significantly decrease tumor markers, including carcinoembryonic antigen (CEA) [MD = -11.64, p < 0.00001]; CA199 [MD = -33.57, p = 0.02]; CA242 [MD = -20.66, p < 0.00001]; CA125 [MD = -12.50, p = 0.0005]. In the comparison of adverse reactions, the incidence rate of Xiaoaiping injection group was significantly lower than that of control group. The funnel plot showed that the left and right sides are basically symmetrical, and it can be considered that there is no obvious publication bias. Conclusion: Xiaoaiping injection combined with chemotherapy has better curative effect and less adverse reactions in the treatment of gastric cancer. However, limited by the quality of the included studies, more high-quality studies are still needed to be verified. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353842], identifier [CRD42022353842].
ABSTRACT
BACKGROUND/AIMS: To explore the role of hepatocyte growth factor (HGF)-loaded polylactic acid-O-carboxymethylated chitosan (PLA-O-CMC) nanoparticles in hepatocyte transplantation (HCT) for treating rat acute liver failure (ALF). METHODS: Five milliliters of hepatocytes respectively treated with conventional culture (group I), PLA-O-CMC nanoparticles (group II) and HGF-loaded PLA-O-CMC nanoparticles (group III) were transplanted into the abdominal cavities of rat with ALF. In group IV, rats were treated as group II except intravenous 10 pg of HGF daily for 7 days, and in group V, rats were given intraperitoneal RPMI-1640. RESULTS: The survival rate on the 14th day after HCT was higher in groups III IV, and II than in group V (p<0.05). Hepatic function in groups II-IV was improved 24 h after HCT (p<0.05, compared with group V). The recovery of hepatic function was the best in group III. In group III, mitotic index was 10.20% on the 5th day after HCT (p<0.05, compared with other groups) and Ki-67 labeling index was 16.8% on the 7th day after HCT (p<0.05, compared with group V). CONCLUSIONS: HGF-loaded PLA-O-CMC nanoparticles can steadily release HGF, and exhibits better tendencies in liver regeneration, survival rate and hepatic function compared with intravenous HGF.
Subject(s)
Chitosan/chemistry , Drug Carriers , Hepatocyte Growth Factor/administration & dosage , Hepatocytes/drug effects , Hepatocytes/transplantation , Lactic Acid/chemistry , Liver Failure, Acute/surgery , Nanoparticles , Polymers/chemistry , Animals , Biomarkers/metabolism , Cells, Cultured , Chemistry, Pharmaceutical , Chitosan/analogs & derivatives , Delayed-Action Preparations , Disease Models, Animal , Female , Hepatocyte Growth Factor/chemistry , Hepatocytes/metabolism , Hepatocytes/pathology , Injections, Intraperitoneal , Injections, Intravenous , Ki-67 Antigen/metabolism , Liver Failure, Acute/metabolism , Liver Failure, Acute/pathology , Liver Failure, Acute/physiopathology , Liver Regeneration/drug effects , Male , Mitotic Index , Polyesters , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
This paper is aimed to observe the hepatocyte growth factor (HGF) loading and delivery ability of polylactic acid and oxygen carboxymethylated chitosan copolyer nanoparticles (PLA-O-CMC NPs). We prepared PLA-O-CMC NPs loaded with HGF by ultrasound in combination with magnetic stirring method. The NPs were characterized by transmission electron microscopy, embedding ratio; drug loading and drug delivery behaviors were observed by ELISA. The characteristics of PLA-O-CMC NPs loaded with HGF showed that the mean size was 139. 82 nm, polydispersity was 0.108, maximal HGF-embedding ratio was 76. 32%. The cumulative HGF release gradually increased in the first 24 hours in vitro, with sharp increasing in the first 7 hours, and moderate and steady increasing in the following 17 hours. The HGF had a burst release in the first 24 hours, and in this process the released HGF took up 36.7% of the whole release. From the second day,the HGF release decreased obviously, while it kept on releasing steadily (45-55 ng/d) for quite long time up to 30 days. The experiment proved that PLA-O-CMC NPs is a favourable carrier of HGF. PLA-O-CMC NPs loaded with HGF could rapidly release HGF in vitro. The released HGF reached the effective drug concentration and maintained the certain effective drug concentration for a long time.
