Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer. METHODS: For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate. RESULTS: There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups. CONCLUSIONS: These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.

Safe temperature range for intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion in a swine model of experimental distal gastrectomy with Billroth II reconstruction.

BACKGROUND: The current study sought to investigate the safety of intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion (IEPCHIP) at different temperatures in a swine model of experimental distal gastrectomy with Billroth II reconstruction. METHODS: Thirty pigs were randomly divided into 5 groups. Two groups were used as the control groups (groups A1 and A2), and 3 groups were used as the perfusion groups (groups B, C and D). Pigs in group A1 received distal gastrectomy with Billroth II reconstruction only. Pigs in groups A2, B, C and D received the same surgery as group A1, followed by IEPCHIP at 37 ± 0.5°C, 42.5 ± 0.5°C, 43.5 ± 0.5°C or 44.5 ± 0.5°C, respectively. The perfusion time was assessed for each pig in group A2 as well as in the perfusion groups, and the perfusions were performed twice for each group. The first perfusion was conducted intraoperatively, and the second perfusion was initiated 1 day after surgery. Data concerning vital signs and hepatic and renal function were collected. Parameters concerning anastomotic healing, the pathology of the anastomotic tissue and abdominal adhesion were compared. RESULTS: The vital signs and hepatic and renal functions of the pigs in groups A1, A2, B and C were not significantly affected by this procedure. In contrast, the vital signs and hepatic and renal functions of the pigs in group D were significantly affected. Compared to the pigs in groups A1, A2 or B, the anastomotic bursting pressure, breaking strength and hydroxyproline content in group C and D pigs were significantly lower. No significant differences were observed in these parameters between groups A1, A2 and B. Abdominal adhesion was more severe in group D pigs. Collagen deposition in group A1, A2 and B pigs was dense in the anastomosis, and inflammatory cell infiltration was observed in group D. CONCLUSIONS: IEPCHIP at 42.5 ± 0.5°C was safe and caused minimal impairments. However, anastomotic healing was affected by perfusion at 43.5 ± 0.5°C and 44.5 ± 0.5°C, and abdominal adhesion was most severe in the group D animals, which were perfused at 44.5 ± 0.5°C.

Functional analysis and molecular docking identify two active short-chain prenyltransferases in the green peach aphid, Myzus persicae.

Short-chain prenyltransferases are responsible for biosynthesis of the C(10)-C(20) precursors of a variety of isoprenoids. We previously isolated two different short-chain prenyltransferases from the green peach aphid, Myzus persicae (MpIPPS1 and MpIPPS2). In this study, the activity of the two aphid prenyltransferases was analyzed in vitro. Kinetic analysis using recombinant enzymes showed that both prenyltransferases could efficiently catalyze the formation of C(10) geranyl diphosphate (GPP) and C(15) farnesyl diphosphate (FPP) from the C(5) substrates isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), and MpIPPS2 had higher catalytic activity than MpIPPS1. Product analysis by gas chromatography-mass spectrometry demonstrated that FPP was generated as the major product, but GPP could be detected at low enzyme concentrations. Molecular docking revealed that MpIPPS2 had higher binding affinity with the substrates DMAPP, IPP, and GPP than MpIPPS1, which supported the experimentally determined kinetic parameters. Molecular docking also identified an amino acid residue (K266) critical to the catalytic activity of both MpIPPS1 and MpIPPS2. This prediction was subsequently confirmed by site-directed mutagenesis, in which a point mutation (K266I) abolished the activity of both MpIPPS1 and MpIPPS2. Our data illustrate that both aphid short-chain prenyltransferases are active forms, which is in contrast to the previously reported results.

[Impact of provincial infrastructure investment on the vulnerability of social-ecological system in China]. / æˆ‘å›½çœåŸŸåŸºç¡€è®¾æ–½æŠ•å ¥å¯¹ç¤¾ä¼š-生态系统脆弱性的影响.

The impact of infrastructure investment on social-economic system or ecological system has been widely discussed, yet, the overall impact of infrastructure investment on social-ecological system (SES) is still unknown. This study summarized the impact mechanism of infrastructure investment on social ecosystem vulnerability. We first sorted out the impact mechanism of infrastructure investment on SES vulnerability, and then empirically analyzed the effect of provincial infrastructure investment on SES vulnerability by using spatial autocorrelation and spatial econometric models on the basis of accounting provincial per capita infrastructure capital stock and comprehensive evaluation of SES vulnerability. The results showed that the infrastructure capital stock per capita at provincial level increased significantly during 2004-2017, with a spatial pattern that the north was higher than the south and the east/west was higher than the middle in China. The provincial SES vulnerability was improved, with spatial distribution characteristics of gradually getting worse from east to west in China. There was positive spatial correlation between provincial infrastructure investment and SES vulnerability, with aggregation distribution characteristics. There was inverted U-shaped relationship between infrastructure investment and SES vulnerability in China, that was, the appropriate investment of infrastructure at early could decrease SES vulnerability, while over-investment would increase it. Our results revealed the overall impact mechanism and dynamic characteristics of infrastructure investment on SES vulnerability, and could provide theoretical and policy-making support for the coordination of infrastructure construction and SES vulnerability governance at the macro level for China.

Odorant Binding Protein C17 Contributes to the Response to Artemisia vulgaris Oil in Tribolium castaneum.

The red flour beetle, Tribolium castaneum (T. castaneum), generates great financial losses to the grain storage and food processing industries. Previous studies have shown that essential oil (EO) from Artemisia vulgaris (A. vulgaris) has strong contact toxicity to larvae of the beetle, and odorant-binding proteins (OBPs) contribute to the defense of larvae against A. vulgaris. However, the functions of OBPs in insects defending against plant oil is still not clear. Here, expression of one OBP gene, TcOBPC17, was significantly induced 12-72 h after EO exposure. Furthermore, compared to the control group, RNA interference (RNAi) against TcOBPC17 resulted in a higher mortality rate after EO treatment, which suggests that TcOBPC17 involves in the defense against EO and induces a declining sensitivity to EO. In addition, the tissue expression profile analysis revealed that the expression of TcOBPC17 was more abundant in the metabolic detoxification organs of the head, fat body, epidermis, and hemolymph than in other larval tissue. The expression profile of developmental stages showed that TcOBPC17 had a higher level in early and late adult stages than in other developmental stages. Taken together, these results suggest that TcOBPC17 could participate in the sequestration process of exogenous toxicants in T. castaneum larvae.

[Comparison study of three methods of digestive tract reconstruction after radical gastrectomy in gastric cancer patients].

OBJECTIVE: To investigate the ideal digestive tract reconstruction methods among three different surgical methods after radical gastrectomy of gastric cancer patients. METHODS: A total of 123 patients who received elective radical gastrectomy for gastric cancer from February 2010 to August 2011 were prospectively enrolled and randomly divided into radical proximal gastrectomy and jejunal interposition group, radical proximal gastrectomy and esophageal with the posterior of residual-stomach group, and radical total gastrectomy and Roux-en-Y esophagojejunostomy group. Patients were followed up for 12 months. Symptoms of reflux esophagitis were observed, gastric emptying tests were done, liver and kidney function was also monitored. The quality of life was documented before operation, and one and twelve months after operation. RESULTS: No significant differences were found among these three groups in the pH value of lower part of esophagus, the blood regular test results and the functional parameters of kidney and liver before and after operation(all P>0.05). Symptoms of reflux esophagitis was reported in 1(2.4%) patients in the jejunal interposition group, 10(24.4%) in esophageal with the posterial of residual-stomach group, and 7(17.1%) in the Roux-en-Y esophagojejunostomy group(P=0.017). There was 1(2.4%), 10(17.1%), and 8(19.5%) patients presented reflux of barium meal in these three groups, respectively (P=0.046). There were no statistically significant difference in PH at the distal esophagus(6.9±0.2 vs. 6.8±0.1 vs. 6.9±0.1, P=0.196). The quality of life was significantly improved one year after surgery in terms of general status, physical function, emotional function, fatigue, nausea/vomiting, pain, constipation, and diarrhea (all P<0.05), with the jejunal interposition superior than the other two methods. CONCLUSION: Three methods of digestive tract reconstruction in radical gastrectomy of gastric cancer patients can improve the health status and the quality of life in gastric cancer patients. Radical proximal gastrectomy and jejunal interposition is the preferred method.

Molecular cloning and characterization of a prenyltransferase from the cotton aphid, Aphis gossypii.

Prenyltransferases play a key role in isoprenoid biosynthesis. Here, a cDNA encoding a prenyltransferase was isolated from the cotton aphid, Aphis gossypii, which consists of 1354 nucleotides and encodes a protein of 394 amino acids (AgIPPS). Subsequent sequencing of AgIPPS genomic DNA resulted in one 3138-bp sequence. Southern blotting analysis indicated that only a single IPPS gene exists in the cotton aphid. Real-time quantitative PCR showed that AgIPPS transcripts were mainly present at the corpora allatum, but small quantity could be detected in tissues other than the corpora allatum. Transcript abundance changed in an alternative manner at different life stages. High expression was observed in embryos, second and forth instar nymphs and adults, but only low level was detected in the first and third instars. Functional expression, activity assay and product analysis revealed that the mature form of AgIPPS (AgIPPS-S) could efficiently convert labeled isopentenyl diphosphate in the presence of dimethylallyl diphosphate to both geranyl diphosphate (GPP) and farnesyl diphosphate (FPP). These data suggested that, unlike the green peach aphid and the pea aphid, the cotton aphid appears to contain only a single IPPS with dual FPP/GPP synthase activity.

Two different farnesyl diphosphate synthase genes exist in the genome of the green peach aphid, Myzus persicae.

Farnesyl diphosphate synthase (FPS; EC 2.5.1.1, 2.5.1.10) catalyzes biosynthesis of farnesyl diphosphate, which is important to insects as the precursor of juvenile hormone and the substrate for (E)-beta-farnesene synthase. Here, two FPS cDNAs were isolated from the green peach aphid, Myzus persicae (EU334430 and EU334431). Their shared identity within the coding region is approximately 82%. The deduced amino acid sequences of the two M. persicae FPS cDNAs have the highly conserved motifs characteristic of most known FPSs. Phylogenetic analyses showed that they are closely related to other insect FPSs. Homology modeling of structures suggested a very good fit between the three-dimensional structures of the two putative M. persicae FPSs (designated as MpFPS1 and MpFPS2) and the avian FPS crystal structure. The corresponding genomic DNA sequences were subsequently determined (EU429295 and EU429296). Sequence comparisons revealed a different splicing pattern between the two MpFPS genes. Furthermore, the two MpFPS genes exhibited a seemingly very primitive gene-splicing pattern at 5' ends but a gene-splicing style similar to mammalian FPS genes at 3' ends. These data, combined with results of Southern blotting, suggest that M. persicae contains two different FPS genes. This is the first report that two different FPS genes exist in a hemipteran insect.