Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer. METHODS: The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis. RESULTS: Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%). CONCLUSION: In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.

Pseudemcibacter aquimaris gen. nov., sp. nov., isolated from an aquaculture farm.

A rod-shaped, Gram-stain-negative, aerobic and non-motile bacterium, designated strain Y4T, was isolated from an aquaculture farm in Xiamen, PR China. Strain Y4T had 94.8, 93.3 and 91.8 % 16S rRNA gene sequence similarity to Paremcibacter congregatus ZYLT, Emcibacter nanhaiensis HTCJW17T and Luteithermobacter gelatinilyticus MEBiC09520T, respectively. The genomic DNA G+C content of strain Y4T was 42.7 mol%. The average amino acid identity and percentage of conserved proteins values between strain Y4T and type strains of the family Emcibacteraceae were 57.9-58.6 % and 44.5-47.6 %, respectively. Optimal growth was observed at 28 °C, at pH 7.0 and with 2 % (w/v) NaCl. The novel strain Y4T required Ca2+, K+ and Mg2+ ions in addition to NaCl for growth. The dominant fatty acids of strain Y4T were summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C14 : 0 2-OH. The polar lipid profile contained phosphatidylethanolamine, phosphatidyglycerol, three unidentified aminolipids, four unidentified aminophospholipids and two unidentified lipids. Cells contained exclusively ubiquinone Q-10. On the basis of the polyphasic analysis, strain Y4T (=MCCC 1K06278T=KCTC 82926T) is considered to represent a novel species in a novel genus of the family Emcibacteraceae, for which the name Pseudemcibacter aquimaris gen. nov., sp. nov. is proposed.

Ribosome-Inactivating Proteins of Bougainvillea glabra Uncovered Polymorphism and Active Site Divergence.

Ribosome-inactivating proteins (RIPs) are toxic proteins that can inhibit protein synthesis. RIPs purified from Bougainvillea have low nonspecific toxicity, showing promise for processing applications in the agricultural and medical fields. However, systematic research on the polymorphism of Bougainvillea RIPs is lacking, and it is worth exploring whether different isoforms differ in their active characteristics. The transcriptional and translational expression of type I RIPs in Bougainvillea glabra leaves was investigated in this study. Seven RIPs exhibited seasonal variation at both the mRNA and protein levels. The isoforms BI4 and BI6 showed the highest transcriptional expression in both the summer and autumn samples. Interestingly, BI6 was not detected in the protein level in any of the samples. However, the bioinformatics analysis showed that RIPs derived from the same species were gathered in a different cluster, and that the active sites changed among the isoforms during evolution. The significant discrepancy in Bougainvillea RIPs mainly locates at both termini of the amino acid sequence, particularly at the C terminus. Post-translational modifications may also exist in Bougainvillea RIPs. It is concluded that the reason for the polymorphism of Bougainvillea RIPs may be that these proteins are encoded by multiple genes due to genetic processes such as gene duplication and mutation. According to the results of sequence analysis, the possible functional differences of B. glabra RIP isoforms are discussed with regard to the observed discrepancy in both active sites and structures.

Structural analysis of proanthocyanidins isolated from fruit stone of Chinese hawthorn with potent antityrosinase and antioxidant activity.

Proanthocyanidins were isolated from fruit stone of Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.). Their structures were analyzed and elucidated by methods of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and high performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS). The results demonstrated that these compounds are complicated mixtures of homo- and heteropolymers consisting of procyanidin/procyanidin gallate and prodelphinidin. They possessed structural heterogeneity in monomer units, polymer length, and interflavan linkage (A-type and B-type). Their antityrosinase and antioxidant activity were then investigated. The results revealed that they can inhibit tyrosinase activities, including the monophenolase activity and the diphenolase activity. In addition, proanthocyanidins possessed potent antioxidant activity. Our studies revealed that proanthocyanidins isolated from fruit stone of Chinese hawthorn may be applied in food, agriculture, pharmaceutical, and cosmetic industries.

Inhibitory kinetics of betaine on beta-N-acetyl-D-glucosaminidase from prawn (Litopenaeus vannamei).

The effects of betaine on prawn beta-N-acetyl-D-glucosaminidase (NAGase) activity for the hydrolysis of p-nitrophenyl-N-acetyl- beta-D-glucosaminide (pNP-NAG) have been studied. The results showed that appropriate concentrations of betaine could lead to reversible inhibition against NAGase, and the IC(50) value was estimated to be 15.00 +/- 0.30 mM. The inhibitory kinetics assay showed that betaine was a mixed type inhibitor with a K(I) value of 9.17 +/- 0.85 mM and a K(IS) value of 45.58 +/- 2.52 mM. The inhibitory model was set, and the microscopic rate constants were determined using the kinetic method of the substrate reaction. The time course of the hydrolysis of pNP-NAG catalyzed by NAGase in the presence of different betaine concentrations showed that at each betaine concentration, the rate decreased with an increase in time until a straight line was approached, indicating that the inhibition of NAGase by betaine is a slow, reversible reaction with fractional residual activity. The fact that k(+0) is much larger than k(+0)(') indicated that the free enzyme molecule is more fragile than the enzyme-substrate complex against betaine. It is suggested that the presence of the substrate offers marked protection of NAGase against inhibition by betaine.