[Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy].

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

DNA marker analysis for pyramided of Fusarium head blight (FHB) resistance QTLs from different germplasm.

A pyramided FHB resistance line of wheat (WSY) was previously developed from three FHB resistant cultivars (Sumai 3, Wangshuibai, and Nobeokabouzu) in the Jiangsu Academy of Agricultural Sciences, China. In the present study, we analyzed the genetic relationship between WSY and the three parental cultivars using DNA markers in order to clarify how many and which resistance genes had accumulated in WSY. We analyzed 282 DNA markers from the 21 wheat chromosomes. WSY was found to include different chromosome regions that harbored putative FHB QTLs of the three parental germplasm. Haplotypes of DNA markers on these QTL regions revealed that the 1BL, 2BL, 5AS, and 7AL QTL regions were from Sumai 3, the 2AS, 2DS, 3AS, and 6BS QTL regions were from Wangshuibai, and the 3BS QTL region was from Nobeokabouzu. This study showed that different resistance genes from the different resistant germplasm had indeed accumulated in WSY. WSY is a potential resistant resource for FHB resistance in wheat breeding programs.

[Effect of glycosides of Tripterygium wilfordii Hook on the reproductive system and major organs of male rats].

Spermatogenesis and turnover of basic nuclear protein synthesis in late elongated spermatids of rat testis were found to be significantly inhibited by glycosides of Tripterygium wilfordii Hook (T II) at a daily dosage of 10 mg/kg for 7 or 13 weeks and 20 mg/kg for 4 or 10 weeks. The number of spermatozoa in the epididymis was found to be reduced and the remaining spermatozoa deformed, showing head swelling, head and tail separation and severe curling of the middle piece. These changes differed from those effected by gossypol treatment. The formazan deposits of sperm mitochondrial enzyme reactions were also reduced. Activities of several enzymes in the heart, liver and kidney were not obviously affected, except for an enhancement of SDH activity in tissues of all 3 organs and ALP in renal tubules, with a slight decrease of ALP in the brush-borders of proximal renal tubules arising as an adaptation to T II toxicity.