Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT

Impacts of Parents’ Divorce on Chinese Children: A Model with Academic Performance as a Mediator

The study examined the impact of parents’ divorce on Chinese children’s well-being. A Chinese theoretical model was tested using Structural Equation Modeling. The sample consisted of 940 Chinese children aged 6-16. The well-being of children from divorced families was compared with that of two-parent and widowed families. The results showed that children’s academic performance mediated the negative impact of divorce on children’s well-being. The societal discriminating attitude towards divorce and single-parent families had a strong negative effect on the children’s well-being. Parenting skills of the custodial parent had more influence on the children’s well-being than the marital conflicts prior to the divorce. Supports from the extended families counterbalanced some negative effects associated with divorce

Knowledge-Enhanced Dual-Channel GCN for Aspect-Based Sentiment Analysis

As a subtask of sentiment analysis, aspect-based sentiment analysis (ABSA) refers to identifying the sentiment polarity of the given aspect. The state-of-the-art ABSA models are developed by using the graph neural networks to deal with the semantics and the syntax of the sentence. These methods are challenged by two issues. For one thing, the semantic-based graph convolution networks fail to capture the relation between aspect and its opinion word. For another, minor attention is assigned to the aspect word within graph convolution, resulting in the introduction of contextual noise. In this work, we propose a knowledge-enhanced dual-channel graph convolutional network. On the task of ABSA, a semantic-based graph convolutional netwok (GCN) and a syntactic-based GCN are established. With respect to semantic learning, the sentence semantics are enhanced by using commonsense knowledge. The multi-head attention mechanism is taken to construct the semantic graph and filter the noise, which facilitates the information aggregation of the aspect and the opinion words. For syntactic information processing, the syntax dependency tree is pruned to remove the irrelevant words, based on which more attention weights are given to the aspect words. Experiments are carried out on four benchmark datasets to evaluate the working performance of the proposed model. Our model significantly outperforms the baseline models and verifies its effectiveness in ABSA tasks

Knowledge-Enhanced Dual-Channel GCN for Aspect-Based Sentiment Analysis

As a subtask of sentiment analysis, aspect-based sentiment analysis (ABSA) refers to identifying the sentiment polarity of the given aspect. The state-of-the-art ABSA models are developed by using the graph neural networks to deal with the semantics and the syntax of the sentence. These methods are challenged by two issues. For one thing, the semantic-based graph convolution networks fail to capture the relation between aspect and its opinion word. For another, minor attention is assigned to the aspect word within graph convolution, resulting in the introduction of contextual noise. In this work, we propose a knowledge-enhanced dual-channel graph convolutional network. On the task of ABSA, a semantic-based graph convolutional netwok (GCN) and a syntactic-based GCN are established. With respect to semantic learning, the sentence semantics are enhanced by using commonsense knowledge. The multi-head attention mechanism is taken to construct the semantic graph and filter the noise, which facilitates the information aggregation of the aspect and the opinion words. For syntactic information processing, the syntax dependency tree is pruned to remove the irrelevant words, based on which more attention weights are given to the aspect words. Experiments are carried out on four benchmark datasets to evaluate the working performance of the proposed model. Our model significantly outperforms the baseline models and verifies its effectiveness in ABSA tasks

Research and application of combined pressure relief technology of roof hydraulic fracturing and deep hole blasting

In order to realize the smooth collapse of high-strength composite roof in 1311 working face of Zhaozhuang Coal Industry company and avoid strong ground pressure disaster caused by large-area roof suspension, firstly, the composite pressure relief mechanism of “cross cutting and longitudinal explosion” is analyzed theoretically, in other words, the secondary propagation radius r of blasting crack is greatly increased on the basis of fracturing damage length R and explosion crack radius a0, which improves the effect of roof pre-cracking, then, based on the industrial test of 1309 working face, the pressure relief process parameters of “cross cutting and longitudinal explosion” are reasonably determined and applied in the field. The results show that: the “cross cutting and longitudinal blasting” composite pressure relief process can increase the density of borehole axial fractures and borehole radial fractures, and the roof separation of roadway in the application area is low; it shows that the “cross cutting and longitudinal blasting” pressure relief process can effectively destroy the integrity of the roof, reduce the stress concentration of the surrounding rock of the roadway, and play a preventive effect on the strong ground pressure disaster

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study

Abstract Background For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. Methods Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. Results We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26–6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06–6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67–4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. Conclusions These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors

Consistent signatures in the human gut microbiome of old- and young-onset colorectal cancer

Abstract The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups

Additional file 1 of The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study

Additional file 1: Fig S1. Flow of study