A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer.

BACKGROUND: The metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI. METHODS: Genes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein-protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription-quantitative real-time PCR (RT-qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes. RESULTS: This study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune-related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells. CONCLUSION: We distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI.

Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients' clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)]. Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis. Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score. Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients' sensitivity to therapeutic drugs.

Effect of preoperative nutrition therapy type and duration on short-time outcomes in gastric cancer patient with gastric outlet obstruction.

OBJECTIVE: To avoid perioperative complications caused malnutrition, nutrition therapy is necessary in gastric outlet obstruction (GOO) patients. Compared to parenteral nutrition (PN), enteral nutrition (EN) is associated with many advantages. This study aimed to investigate whether preoperative EN has beneficial clinical effects compared to preoperative PN in gastric cancer patients with GOO undergoing surgery. METHODS: According to the methods of preoperative nutrition therapy, 143 patients were divided into EN group (n=42) and PN group (n=101) between January 2013 and December 2017 at the Chinese People's Liberation Army General Hospital. Multiple logistic regression models were used to assess the association between the methods of preoperative nutrition therapy and postoperative day of flatus passage. The generalized additive model and two-piecewise linear regression model were used to calculate the inflection point of the preoperative nutritional therapy time on the postoperative day of flatus passage in the PN group. RESULTS: EN shortened the postoperative day of flatus passage in gastric cancer patients with GOO, which is a protective factor, especially in patients who underwent non-radical operations and the postoperative day of flatus passage reduced when the preoperative PN therapy was up to 3 d and a longer PN therapy (>3 d) did not accelerate the postoperative recovery of gastrointestinal functions. CONCLUSIONS: Preoperative EN therapy would benefit gastric cancer patients with GOO by accelerating postoperative recovery. For patients with absolute obstruction, no more than 3-day PN therapy is recommended if patients can tolerate general anesthesia and surgery.

Advantages of intraoperative nerve monitoring in endoscopic thyroidectomy for papillary thyroid carcinoma.

BACKGROUND: This study aimed to evaluate the feasibility and effectiveness of intraoperative nerve monitoring (IONM) for reducing the recurrent laryngeal nerve (RLN) injury risk during central compartment lymph node dissection in endoscopic thyroidectomy of papillary thyroid carcinoma (PTC). METHODS: The prospective cohort consisted of 69 patients diagnosed with PTC undergoing endoscopic thyroidectomy via the areola approach with (N.=42) or without IONM (N.=27). Multiple logistic regression models were used to assess the association between IONM and postoperative temporary vocal cord palsy or number of retrieved lymph nodes. RESULTS: IONM was a protective factor against temporary RLN injury. IONM use was positively correlated with number of retrieved lymph nodes (ß=1.563, P=0.003). After adjustment for operation type, the result remained significant (ß=1.581, P<0.001). CONCLUSIONS: IONM use reduced the risk of temporary vocal cord palsy and increased the number of retrieved lymph nodes in endoscopic thyroidectomy via the areola approach for patients with PTC.

Correction to: Incorporating pleiotropic quantitative trait loci in dissection of complex traits: seed yield in rapeseed as an example.

The article "Incorporating pleiotropic quantitative trait loci in dissection of complex traits: seed yield in rapeseed as an example", written by J. Zou et al, was originally published Online First without open access.

Hybrid Performance of an Immortalized F2 Rapeseed Population Is Driven by Additive, Dominance, and Epistatic Effects.

Genomics-based prediction of hybrid performance promises to boost selection gain. The main goal of our study was to investigate the relevance of additive, dominance, and epistatic effects for determining hybrid seed yield in a biparental rapeseed population. We re-analyzed 60,000 SNP array and seed yield data points from an immortalized F2 population comprised of 318 hybrids and 180 parental lines by performing genome-wide QTL mapping and predictions in combination with five-fold cross-validation. Moreover, an additional set of 37 hybrids were genotyped and phenotyped in an independent environment. The decomposition of the phenotypic variance components and the cross-validated results of the QTL mapping and genome-wide predictions revealed that the hybrid performance in rapeseed was driven by a mix of additive, dominance, and epistatic effects. Interestingly, the genome-wide prediction accuracy in the additional 37 hybrids remained high when modeling exclusively additive effects but was severely reduced when dominance or epistatic effects were also included. This loss in accuracy was most likely caused by more pronounced interactions of environments with dominance and epistatic effects than with additive effects. Consequently, the development of robust hybrid prediction models, including dominance and epistatic effects, required much deeper phenotyping in multi-environmental trials.

Breeding histories and selection criteria for oilseed rape in Europe and China identified by genome wide pedigree dissection.

Selection breeding has played a key role in the improvement of seed yield and quality in oilseed rape (Brassica napus L.). We genotyped Tapidor (European), Ningyou7 (Chinese) and their progenitors with the Brassica 60 K Illumina Infinium SNP array and mapped a total of 29,347 SNP markers onto the reference genome of Darmor-bzh. Identity by descent (IBD) refers to a haplotype segment of a chromosome inherited from a shared common ancestor. IBDs identified on the C subgenome were larger than those on the A subgenome within both the Tapidor and Ningyou7 pedigrees. IBD number and length were greater in the Ningyou7 pedigree than in the Tapidor pedigree. Seventy nine QTLs for flowering time, seed quality and root morphology traits were identified in the IBDs of Tapidor and Ningyou7. Many more candidate genes had been selected within the Ningyou7 pedigree than within the Tapidor pedigree. These results highlight differences in the transfer of favorable gene clusters controlling key traits during selection breeding in Europe and China.

Incorporating pleiotropic quantitative trait loci in dissection of complex traits: seed yield in rapeseed as an example.

KEY MESSAGE: A comprehensive linkage atlas for seed yield in rapeseed. Most agronomic traits of interest for crop improvement (including seed yield) are highly complex quantitative traits controlled by numerous genetic loci, which brings challenges for comprehensively capturing associated markers/genes. We propose that multiple trait interactions underlie complex traits such as seed yield, and that considering these component traits and their interactions can dissect individual quantitative trait loci (QTL) effects more effectively and improve yield predictions. Using a segregating rapeseed (Brassica napus) population, we analyzed a large set of trait data generated in 19 independent experiments to investigate correlations between seed yield and other complex traits, and further identified QTL in this population with a SNP-based genetic bin map. A total of 1904 consensus QTL accounting for 22 traits, including 80 QTL directly affecting seed yield, were anchored to the B. napus reference sequence. Through trait association analysis and QTL meta-analysis, we identified a total of 525 indivisible QTL that either directly or indirectly contributed to seed yield, of which 295 QTL were detected across multiple environments. A majority (81.5%) of the 525 QTL were pleiotropic. By considering associations between traits, we identified 25 yield-related QTL previously ignored due to contrasting genetic effects, as well as 31 QTL with minor complementary effects. Implementation of the 525 QTL in genomic prediction models improved seed yield prediction accuracy. Dissecting the genetic and phenotypic interrelationships underlying complex quantitative traits using this method will provide valuable insights for genomics-based crop improvement.

Introgressing Subgenome Components from Brassica rapa and B. carinata to B. juncea for Broadening Its Genetic Base and Exploring Intersubgenomic Heterosis.

Brassica juncea (AjAjBjBj), is an allotetraploid that arose from two diploid species, B. rapa (ArAr) and B. nigra (BnBn). It is an old oilseed crop with unique favorable traits, but the genetic improvement on this species is limited. We developed an approach to broaden its genetic base within several generations by intensive selection. The Ar subgenome from the Asian oil crop B. rapa (ArAr) and the Bc subgenome from the African oil crop B. carinata (BcBcCcCc) were combined in a synthesized allohexaploid (ArArBcBcCcCc), which was crossed with traditional B. juncea to generate pentaploid F1 hybrids (ArAjBcBjCc), with subsequent self-pollination to obtain newly synthesized B. juncea (Ar/jAr/jBc/jBc/j). After intensive cytological screening and phenotypic selection of fertility and agronomic traits, a population of new-type B. juncea was obtained and was found to be genetically stable at the F6 generation. The new-type B. juncea possesses good fertility and rich genetic diversity and is distinctly divergent but not isolated from traditional B. juncea, as revealed by population genetic analysis with molecular markers. More than half of its genome was modified, showing exotic introgression and novel variation. In addition to the improvement in some traits of the new-type B. juncea lines, a considerable potential for heterosis was observed in inter-subgenomic hybrids between new-type B. juncea lines and traditional B. juncea accessions. The new-type B. juncea exhibited a stable chromosome number and a novel genome composition through multiple generations, providing insight into how to significantly broaden the genetic base of crops with subgenome introgression from their related species and the potential of exploring inter-subgenomic heterosis for hybrid breeding.

Seed Quality Traits Can Be Predicted with High Accuracy in Brassica napus Using Genomic Data.

Improving seed oil yield and quality are central targets in rapeseed (Brassica napus) breeding. The primary goal of our study was to examine and compare the potential and the limits of marker-assisted selection and genome-wide prediction of six important seed quality traits of B. napus. Our study is based on a bi-parental population comprising 202 doubled haploid lines and a diverse validation set including 117 B. napus inbred lines derived from interspecific crosses between B. rapa and B. carinata. We used phenotypic data for seed oil, protein, erucic acid, linolenic acid, stearic acid, and glucosinolate content. All lines were genotyped with a 60k SNP array. We performed five-fold cross-validations in combination with linkage mapping and four genome-wide prediction approaches in the bi-parental population. Quantitative trait loci (QTL) with large effects were detected for erucic acid, stearic acid, and glucosinolate content, blazing the trail for marker-assisted selection. Despite substantial differences in the complexity of the genetic architecture of the six traits, genome-wide prediction models had only minor impacts on the prediction accuracies. We evaluated the effects of training population size, marker density and phenotyping intensity on the prediction accuracy. The prediction accuracy in the independent and genetically very distinct validation set still amounted to 0.14 for protein content and 0.17 for oil content reflecting the utility of the developed calibration models even in very diverse backgrounds.

Co-linearity and divergence of the A subgenome of Brassica juncea compared with other Brassica species carrying different A subgenomes.

BACKGROUND: There are three basic Brassica genomes (A, B, and C) and three parallel sets of subgenomes distinguished in the diploid Brassica (i.e.: B. rapa, A(r)A(r); B. nigra, B(ni)B(ni); B. oleracea, C(o)C(o)) and the derived allotetraploid species (i.e.: B. juncea, A(j)A(j)B(j)B(j); B. napus, A(n)A(n)C(n)C(n); B. carinata, B(c)B(c)C(c)C(c)). To understand subgenome differentiation in B. juncea in comparison to other A genome-carrying Brassica species (B. rapa and B. napus), we constructed a dense genetic linkage map of B. juncea, and conducted population genetic analysis on diverse lines of the three A-genome carrying Brassica species using a genotyping-by-sequencing approach (DArT-seq). RESULTS: A dense genetic linkage map of B. juncea was constructed using an F2 population derived from Sichuan Yellow/Purple Mustard. The map included 3329 DArT-seq markers on 18 linkage groups and covered 1579 cM with an average density of two markers per cM. Based on this map and the alignment of the marker sequences with the physical genome of Arabidopsis thaliana, we observed strong co-linearity of the ancestral blocks among the different A subgenomes but also considerable block variation. Comparative analyses at the level of genome sequences of B. rapa and B. napus, and marker sequence anchored on the genetic map of B. juncea, revealed a total of 30 potential inversion events across large segments and 20 potential translocation events among the three A subgenomes. Population genetic analysis on 26 accessions of the three A genome-carrying Brassica species showed that the highest genetic distance were estimated when comparing A(j)-A(n) than between A(n)-A(r) and A(j)-A(r) subgenome pairs. CONCLUSIONS: The development of the dense genetic linkage map of B. juncea with informative DArT-seq marker sequences and availability of the reference sequences of the A(r), and A(n)C(n) genomes allowed us to compare the A subgenome structure of B. juncea (A(j)) . Our results suggest that strong co-linearity exists among the three A Brassica genomes (A(r), A(n) and A(j)) but with apparent subgenomic variation. Population genetic analysis on three A-genome carrying Brassica species support the idea that B. juncea has distinct genomic diversity, and/or evolved from a different A genome progenitor of B. napus.

Laparoscopic repair of esophageal hiatal hernia.

This study was to appraise safety and feasibility of laparoscopic approach and investigate the clinical effects of laparoscopic tension-free repair of esophageal hiatal hernia using mesh. From August 2006 to July 2009, 24 patients with esophageal hiatal hernia underwent laparoscopic repair. Twenty-three patients received laparoscopic tension-free repair using mesh, at the same time, Toupet or Dor partial fundoplication was performed. One patient was converted to open surgery. The average operating time was 90 min (70-210 min) and the blood loss was between 10-110 mL. There was no death. The mean postoperative hospital stay was 5 days (3-30 days). During a follow-up period of 12-20 months (mean 15 months), there was no recurrence of the hernia, and no complication with use of mesh. The present study suggested that laparoscopic approach was secure and minimally invasive operation for esophageal hiatal hernia and the use of mesh could reduce recurrence rate.

Laparoscopic Repair of Esophageal Hiatal Hernia / 华中科技大学学报（医学）（英德文版）

This study was to appraise safety and feasibility of laparoscopic approach and investigate the clinical effects of laparoscopic tension-free repair of esophageal hiatal hernia using mesh.From August 2006 to July 2009,24 patients with esophageal hiatal hernia underwent laparoscopic repair.Twenty-three patients received laparoscopic tension-free repair using mesh,at the same time,Toupet or Dor partial fundoplication was performed.One patient was converted to open surgery.The average operating time was 90 min (70-210 min) and the blood loss was between 10-110 mL.There was no death.The mean postoperative hospital stay was 5 days (3-30 days).During a follow-up period of 12-20 months (mean 15 months),there was no recurrence of the hernia,and no complication with use of mesh.The present study suggested that laparoscopic approach was secure and minimally invasive operation for esophageal hiatal hernia and the use of mesh could reduce recurrence rate.

[Laparoscopic tension-free repair of umbilical hernia].

OBJECTIVE: To investigate the clinical effects of laparoscopic tension-free repair of umbilical hernia using mesh. METHODS: Form August 2006 to April 2009, 26 patients with umbilical hernia were repaired with mesh under laparoscopy. After the tissues surrounding umbilical perforation were separated by using ultrasonic scalpel, the mesh was stapled to the hernia edge with under laparoscopy. The efficacy of this procedures was analyzed in this study. RESULTS: The tension-free repairing operations were completed successfully in the 26 patients under laparoscopy. The patients felt slight pain and began eating normally on the second day after the operation. The mean operation time was 35 min (30 - 45 min) and the mean blood loss was 8 ml (5 - 15 ml). No operative death and infection occurred postoperatively. The mean postoperative hospital stay was 5 days (3 - 7 days). The patients were followed up for 3 - 25 months (mean 14 months), no recurrence of the hernia occurred in this group.Patients were satisfied with the operation. CONCLUSIONS: Tension-free repairing of umbilical hernia with mesh under laparoscopy is a minimally invasive operation with fast recovery, few complications, it's in line with the principle of tension-free repair for hernia.