RESUMEN
Introduction: Plectropomus leopardus, a commercially significant marine fish, is primarily found in the Western Pacific regions and along the coast of Southeast Asia. A thorough analysis of the molecular mechanisms involved in sex differentiation is crucial for gaining a comprehensive understanding of gonadal development and improving sex control breeding. However, the relevant fundamental studies of P. leopardus are relatively lacking. Methods: In this study, a genome-wide association study (GWAS) was conducted to investigate the genetic basis mechanism of sex differentiation and gonadal developmental traits in P. leopardus utilizing about 6,850,000 high-quality single-nucleotide polymorphisms (SNPs) derived from 168 individuals (including 126 females and 42 males) by the genome-wide efficient mixed-model association (GEMMA) algorithm. Results: The results of these single-trait GWASs showed that 46 SNP loci (-log10 p > 7) significantly associated with sex differentiation, and gonadal development traits were distributed in multiple different chromosomes, which suggested the analyzed traits were all complex traits under multi-locus control. A total of 1,838 potential candidate genes were obtained by considering a less-stringent threshold (-log10 p > 6) and ±100 kb regions surrounding the significant genomic loci. Moreover, 31 candidate genes were identified through a comprehensive analysis of significant GWAS peaks, gene ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, including taf7, ddx6, apoeb, sgk1, a2m, usf1, hsd3b7, dll4, xbp1, tet3, esr1, and gli3. These trait-associated genes have been shown to be involved in germline development, male sex differentiation, gonad morphogenesis, hormone receptor binding, oocyte development, male gonad development, steroidogenesis, estrogen-synthetic pathway, etc. Discussion: In the present study, multiple genomic loci of P. leopardus associated with sex differentiation and gonadal development traits were identified for the first time by using GWAS, providing a valuable resource for further research on the molecular genetic mechanism and sex control in P. leopardus. Our results also can contribute to understanding the genetic basis of the sex differentiation mechanism and gonadal development process in grouper fish.
RESUMEN
OBJECTIVE: To evaluate the therapeutic efficacy and adverse reaction of Aidi Injection (ADI) combined with FOLFOX4 regimen for treatment of patients with advanced colorectal cancer, and controlled with those of FOLFOX4 regimen alone. METHODS: One hundred and seventeen patients were randomized into two groups. All received FOLFOX4 regimen, i.e. Oxaliplatin 85 mg/m2 intravenous dripping in 2 h on day 1, leucovorin CF 200 mg/m2 intravenous dripping and 5-FU 400 mg/m2 intravenous injection followed with 600 mg/m2 continuous infusion by micro-pump in 22 h on day 1 and 2, 14 days as one cycle. Besides, to the treatment group (65 patients), ADI was administered additionally by adding 60 mL ADI in 250 mL 5% glucose for intravenous dripping every day for 10 successive days, while to the control group (52 patients), no additional medication was given. RESULTS: The response rate in the treatment group was 44.62%, and in the control group 30.77% (P = 0.126), the KPS score improving rate in the two groups was 66.15% and 40.38% respectively (P = 0.005), the 1-year survival rate was 53.85% and 40.38% respectively (P = 0.148), and the adverse reaction presented in the treatment group was greatly less than that in the control group (P < 0.05). CONCLUSION: ADI in combining with FOLFOX4 regimen can enhance the efficacy, reduce the adverse reaction of chemotherapy in treating advanced colorectal cancer, and could also improve the quality of life and prolong the survival time of patients.