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Objective To investigate the relationship between daily intake of B vitamins (vitamins B1, B2, B6 and niacin) and chronic constipation and chronic diarrhea. Methods Data of 3 durations (2005-2006, 2007-2008 and 2009-2010) from National Health and Nutrition Examination Survey (NHANES) database were collected and retrospectively analyzed. For the 13 788 participants, their intake of vitamin B1, B2, B6, and niacin were assessed through a 24-hour dietary recall interview. Multivariate logistic regression analysis was employed to explore the correlation between B vitamins and chronic constipation and chronic diarrhea. Additionally, sensitivity analysis and curve fitting correlation analysis were conducted to further elucidate the observed relationships. Results Among the subjects who were enrolled in the study, 2 520 (18.28%) were diagnosed with chronic constipation, while 2 138 (15.51%) were diagnosed with chronic diarrhea. Multivariate logistic regression analysis and sensitivity analysis indicated linear correlations between the intake of vitamin B1, niacin and vitamin B6 and the occurrence of chronic constipation and chronic diarrhea. An increase in the daily intake of these nutrients potentially reduced the risk of chronic constipation, but also increased the risk of chronic diarrhea (P < 0.05). Conclusion Daily intake of vitamins B1, B2, B6 and niacin is correlated with the occurrence of chronic constipation and chronic diarrhea.

Abstract The notion of topological insulators (TIs), characterized by an insulating bulk and conducting topological surface states, can be extended to higher-order topological insulators (HOTIs) hosting gapless modes localized at the boundaries of two or more dimensions lower than the insulating bulk. In this work, by performing high-resolution angle-resolved photoemission spectroscopy (ARPES) measurements with submicron spatial and spin resolution, we systematically investigate the electronic structure and spin texture of quasi-one-dimensional (1D) HOTI candidate Bi4Br4. In contrast to the bulk-state-dominant spectra on the (001) surface, we observe gapped surface states on the (100) surface, whose dispersion and spin-polarization agree well with our ab-initio calculations. Moreover, we reveal in-gap states connecting the surface valence and conduction bands, which is a signature of the hinge states inside the (100) surface gap. Our findings provide compelling evidence for the HOTI phase of Bi4Br4. The identification of the higher-order topological phase promises applications based on 1D spin-momentum locked current in electronic and spintronic devices.

Background It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. Methods and findings This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus [greater than or equal to]5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade [greater than or equal to] 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade [greater than or equal to] 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. Conclusions The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. Trial Registration ClinicalTrials.gov Identifier: NCT03493048., Author(s): De-Shen Wang 1, Chao Ren 1, Shan-Shan Li 2, William Pat Fong 1, Xiao-Jun Wu 3, Jian Xiao 2,4, Bin-Kui Li 5, Yun Zheng 5, Pei-Rong Ding 3, Gong [...]

Since its introduction into China, the film Dune has sparked heated discussions among Chinese moviegoers. This paper explores the sense of cosmic community embedded in Dune, and its cinematic aesthetics conveyed to audiences through the information dissemination path. This paper identifies the hierarchical analysis method as the main research method, first identifies the definition of cosmic community in terms of content, and then conducts an appreciation of the sense of cosmic community in the contextual beauty of “Dune”. The algorithmic framework is established by building a model of the hierarchical analysis method, while the priority weight allocation coefficient is calculated afterward to determine the priority weight of the program, and the results are evaluated using the fuzzy preference evaluation method. The data showed that the highest ratio of movie viewers who liked science and technology very much or more was 36.09% and 35.49%, respectively, while the ratio of movie viewers who were interested in the topics of universe and space exploration was 48.8%. The rating screen effects and movie music scored out of 10, and the average audience rating was above 8.2. And Dune belongs to the topic of cosmic exploration, indicating that at least in terms of the movie audience, Dune already has a large audience base in the early stage, which is one of the sources of the movie’s enthusiasm. This paper is feasible and meaningful to explore the research direction of Dune’s cosmic community of contextual beauty from the contextual level.

The development of the Internet era acts on every change brought by spatial design so that the application of virtual reality technology in spatial design solutions begins to emerge. In this paper, firstly, combining the general process of visualization and the characteristics of visual variables, seven visual variables are selected for preliminary 3D visual representation, and their applicability under virtual reality space is analyzed. The HSV color space is also used for visual coding. According to the intuitive nature of visual perception of spatial design, a multiple visual variables mapping model based on VR is proposed. Considering the sequential characteristics of spatial design, PCA-LSTM spatial design classification model is proposed, and virtual space is applied in spatial design by local changes of the top surface, ground surface, and vertical interface. The simulation experiments are conducted by selecting SVM, BP neural network, and LSTM network as the comparison algorithms, and the results show that the accuracy of both the training set and the test set is found to be improved based on the PCA-LSTM classification model for spatial design classification, which is 4.9% and 9.49% higher than the traditional LSTM algorithm, respectively, verifying the PCA-LSTM for spatial design The effectiveness of PCA-LSTM for spatial design classification is verified. This study cleverly uses the design technique of virtual space to better apply virtual space in spatial design.

This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved. Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions. Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar. P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice. [ABSTRACT FROM AUTHOR]