Correlation of the intestinal flora and its metabolites with the colonic transport function in functional constipation

BackgroundFunctional constipation (FC) is a clinically frequent intestinal disorder. A growing body of evidence emphasizes the link between intestinal microecological imbalance and constipation. However, the microbiota composition associated with FC and the mechanisms by which metabolites influence gut motility remain poorly understood.MethodsStool samples were collected from 60 participants (20 FC patients with delayed colonic transit time, 20 FC patients with normal colonic transit time, and 20 healthy controls), and macrogenomics and metabolomics were used to assess the differences in the microbiota and metabolite composition of different colonic transit functions in FC. In addition to assessing clinical symptoms, this study aimed to better understand how intestinal flora contributed to impaired gut motility in FC patients.ResultsSignificant microbiota taxonomic differences were observed across different gut dynamics in FC; Alistipes, Akkermansia, Oscillibacter, Ruthenibacterium, Alistipes_onderdonkii, and Ruthenibacterium_lactatiformans were key bacteria in FC patients with delayed colonic transit time; Roseburia and Klebsiella_pneumoniae were key bacteria in FC patients with normal colonic transit time; and Escherichia, Enterobacter, Escherichia_coli, Ruminococcus gnavus, Enterobacter_cloacae_complex, and Megamonas_funiformis were the key organisms in healthy controls. The metabolomics analysis revealed three differentially abundant short-chain fatty acids: acetic acid, propionic acid, and butyric acid. Furthermore, there were 11 differentially abundant bile acids, including β-muricholic acid and nor-deoxycholic acid. Correlation analysis revealed significant correlations between the 14 differential bacteria and the 14 metabolites, Notably, Roseburia was positively correlated with butyrate and acetate levels (FDR < 0.05). In addition, Oscillibacter showed positive correlations with several BAs, including nor-deoxycholic acid, isoallolithocholic acid, α-muricholic acid, β-muricholic acid, 5α-cholanic acid-3α-ol, and dehydrolithocholic acid (FDR < 0.05). The Spearman’s |r |value >0.6 combination in the correlation analysis between fecal differential bacteria and differentially abundant metabolites revealed an AUC value of 0.854 between FC patients and healthy controls, indicating good predictive ability.ConclusionThe identified differences in the composition and metabolites of different colonic transmission-dynamic microbiota in FC further our understanding of the underlying mechanisms involved in FC pathogenesis and may provide new insights into diagnostics and therapeutic interventions

Skywork: A More Open Bilingual Foundation Model

In this technical report, we present Skywork-13B, a family of large language models (LLMs) trained on a corpus of over 3.2 trillion tokens drawn from both English and Chinese texts. This bilingual foundation model is the most extensively trained and openly published LLMs of comparable size to date. We introduce a two-stage training methodology using a segmented corpus, targeting general purpose training and then domain-specific enhancement training, respectively. We show that our model not only excels on popular benchmarks, but also achieves \emph{state of the art} performance in Chinese language modeling on diverse domains. Furthermore, we propose a novel leakage detection method, demonstrating that test data contamination is a pressing issue warranting further investigation by the LLM community. To spur future research, we release Skywork-13B along with checkpoints obtained during intermediate stages of the training process. We are also releasing part of our SkyPile corpus, a collection of over 150 billion tokens of web text, which is the largest high quality open Chinese pre-training corpus to date. We hope Skywork-13B and our open corpus will serve as a valuable open-source resource to democratize access to high-quality LLMs

Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.</p> <p>Methods</p> <p>In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes.</p> <p>Results</p> <p>One hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (<it>P </it>< 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; <it>P </it>< 0.001) and vomiting (12.4% vs. 2.0%; <it>P </it>= 0.005).</p> <p>Conclusions</p> <p>Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00136201</p