Numerical Simulation of Proppant Transport in Major and Branching Fractures Based on CFD-DEM.

This research investigated the effect of branching fracture, proppant, and fracturing fluid on proppant transport based on the CFD-DEM coupling model. The obtained results show that the balance height of embankment in the major fracture decreases gradually with increasing angle between major and branching fractures, while it increases gradually in the branching fracture. This is because the additional resistance of fracturing fluid flow at the joint increases with increasing angle, leading to the decrease of the fracturing fluid velocity. The proppant is prone to settling in branching fractures, resulting in the increase of embankment height in the branching fracture. At angles of 45, 60, and 90°, as the diameter of the proppant increases from 0.8 to 1.1 mm, the balance height of embankment increases slightly in the major fracture, while it decreases in the branching fracture. The frictional resistance of the fracture wall enhances the difficulty of large proppant entering the branching fracture, resulting in a decrease in the amount of proppant entering the branching fracture and a decrease of the balance height of embankment in the branching fracture. In the low-viscosity fracturing fluid, the proppant quickly deposits at the bottom of the fracture as it enters the fracture. Improving the viscosity of the fracturing fluid can significantly enhance its ability to transport the proppant. The proppant is less likely to quickly settle in high-viscosity fracturing fluids, especially when the fracturing fluid viscosity exceeds 50 mPa·s.

Potential candidates for liver resection in liver-confined advanced HCC: a Chinese multicenter observational study.

Background: Advanced hepatocellular carcinoma (HCC) is characterized as symptomatic tumors [performance status (PS) score of 1-2], vascular invasion and extrahepatic spread, but patients with PS1 alone may be eliminated from this stage. Although liver resection is used for liver-confined HCC, its role in patients with PS1 alone remains controversial. Therefore, we aimed to explore its application in such patients and identify potential candidates. Methods: Eligible liver-confined HCC patients undergoing liver resection were retrospectively screened in 15 Chinese tertiary hospitals, with limited tumor burden, liver function and PS scores. Cox-regression survival analysis was used to investigate the prognostic factors and develop a risk-scoring system, according to which patients were substratified using fitting curves and the predictive values of PS were explored in each stratification. Results: From January 2010 to October 2021, 1535 consecutive patients were selected. In the whole cohort, PS, AFP, tumor size and albumin were correlated with survival (adjusted P<0.05), based on which risk scores of every patient were calculated and ranged from 0 to 18. Fitting curve analysis demonstrated that the prognostic abilities of PS varied with risk scores and that the patients should be divided into three risk stratifications. Importantly, in the low-risk stratification, PS lost its prognostic value, and patients with PS1 alone achieved a satisfactory 5-year survival rate of 78.0%, which was comparable with that PS0 patients (84.6%). Conclusion: Selected patients with PS1 alone and an ideal baseline condition may benefit from liver resection and may migrate forward to BCLC stage A.

A New inversion method of the initial state of Annulus in killing.

Blowout is a major safety concern for well control in oil and gas well engineering and well killing is an important technical means to avoid blowout. Mastering the initial state of the wellbore is the basis to ensure well killing. The traditional gas column model cannot effectively explain the development law of wellbore pressure. Therefore, this paper is based on the actual killing conditions and the principle of gas-liquid two-phase flow. This paper establishes the physical model and mathematical model of the initial state of the wellbore annulus under overflow conditions. By means of the finite difference method and cyclic iteration calculation, the initial state of the wellbore annulus can be accurately inverted, and the calculation results are verified by an example. The results show that, when the wellhead pressure is determined, the wellbore pressure distribution and annular air phase distribution are more reasonable and the initial length of the overflow section is larger, the calculation results of the inversion method are closer to the actual engineering situation. The findings of this study can help to better understand wellbore state before killing and provide a theoretical basis for optimizing killing parameters, which is of great significance for avoiding well control safety risks during killing.

Succession of the Gut Microbiome in the Tibetan Population of Minjiang River Basin.

Tibetans are one of the oldest ethnic groups in China and South Asia. Based on the analysis of 1,059 Tibetans in the Minjiang River basin at an altitude of 500-4,001 m, we found that the dominant phyla of the Tibetan population were Bacteroidota and Firmicutes, and the main genera were Prevotella and Bacteroides, which were mostly in consistent with other nationalities. We further evaluated in total 115 parameters of seven categories, and results showed that altitude was the most important factor affecting the variation in the microbial community. In the process of emigration from high altitudes to the plain, the gut microbial composition of late emigrants was similar to that of plateau aborigines. In addition, regarding immigration from low altitude to high altitude, the microbial community became more similar to that of high altitude population with the increase of immigration time. Changes in these microbes are related to the metabolism, disease incidence and cell functions of the Tibetan population. The results of other two cohorts (AGP and Z208) also showed the impact of altitude on the microbial community. Our study demonstrated that altitude of habitation is an important factor affecting the enterotype of the microflora in the Tibetan population and the study also provided a basis to explore the interaction of impact parameters with gut microbiome for host health and diseases.

Turbulent Drag Reduction with an Ultra-High-Molecular-Weight Water-Soluble Polymer in Slick-Water Hydrofracking.

Water-soluble polymers as drag reducers have been widely utilized in slick-water for fracturing shale oil and gas reservoirs. However, the low viscosity characteristics, high operating costs, and freshwater consumption of conventional friction reducers limit their practical use in deeper oil and gas reservoirs. Therefore, a high viscosity water-soluble friction reducer (HVFR), poly-(acrylamide-co-acrylic acid-co-2-acrylamido-2-methylpropanesulphonic acid), was synthesized via free radical polymerization in aqueous solution. The molecular weight, solubility, rheological behavior, and drag reduction performance of HVFR were thoroughly investigated. The results showed that the viscosity-average molecular weight of HVFR is 23.2 × 106 g⋅mol-1. The HVFR powder could be quickly dissolved in water within 240 s under 700 rpm. The storage modulus (G') and loss modulus (G″) as well as viscosity of the solutions increased with an increase in polymer concentration. At a concentration of 1700 mg⋅L-1, HVFR solution shows 67% viscosity retention rate after heating from 30 to 90 °C, and the viscosity retention rate of HVFR solution when increasing CNaCl to 21,000 mg⋅L-1 is 66%. HVFR exhibits significant drag reduction performance for both low viscosity and high viscosity. A maximum drag reduction of 80.2% is attained from HVFR at 400 mg⋅L-1 with 5.0 mPa⋅s, and drag reduction of HVFR is 75.1% at 1700 mg⋅L-1 with 30.2 mPa⋅s. These findings not only indicate the prospective use of HVFR in slick-water hydrofracking, but also shed light on the design of novel friction reducers utilized in the oil and gas industry.

Identify optimal HAP series scores for unresectable HCC patients undergoing TACE plus sorafenib: A Chinese multicenter observational study.

Background: Hepatoma arterial-embolization prognostic (HAP) series scores have been proposed for prognostic prediction in patients with unresectable hepatocellular carcinoma (uHCC) undergoing transarterial chemoembolization (TACE). However, their prognostic value in TACE plus sorafenib (TACE-S) remains unknown. Here, we aim to evaluate their prognostic performance in such conditions and identify the best model for this combination therapy. Methods: Between January 2012 and December 2018, consecutive patients with uHCC receiving TACE-S were recruited from 15 tertiary hospitals in China. Cox regression analyses were used to investigate the prognostic values of baseline factors and every scoring system. Their prognostic performance and discriminatory performance were evaluated and confirmed in subgroup analyses. Results: A total of 404 patients were enrolled. In the whole cohort, the median follow-up period was 44.2 (interquartile range (IQR), 33.2-60.7) months, the median overall survival (OS) time was 13.2 months, and 336 (83.2%) patients died at the end of the follow-up period. According to multivariate analyses, HAP series scores were independent prognostic indicators of OS. In addition, the C-index, Akaike information criterion (AIC) values, and time-dependent area under the receiver operating characteristic (ROC) curve (AUC) indicated that modified HAP (mHAP)-III had the best predictive performance. Furthermore, the results remained consistent in most subsets of patients. Conclusion: HAP series scores exhibited good predictive ability in uHCC patients accepting TACE-S, and the mHAP-III score was found to be superior to the other HAP series scores in predicting OS. Future prospective high-quality studies should be conducted to confirm our results and help with treatment decision-making.

The Association of Gut Microbiota With Osteoporosis Is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort.

CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

A Joint Low-Rank and Sparse Method for Reference Signal Purification in DTMB-Based Passive Bistatic Radar.

In a digital terrestrial multimedia broadcasting (DTMB)-based passive bistatic radar (PBR) system, the received reference signal often suffers from serious multipath effect, which decreases the detection ability of low-observable targets in urban environments. In order to improve the target detection performance, a novel reference signal purification method based on the low-rank and sparse feature is proposed in this paper. Specifically, this method firstly performs synchronization operations to the received reference signal and thus obtains the corresponding pseudo-noise (PN) sequences. Then, by innovatively exploiting the inherent low-rank structure of DTMB signals, the noise component in PN sequences is reduced. After that, a temporal correlation (TC)-based adaptive orthogonal matching pursuit (OMP) method, i.e., TC-AOMP, is performed to acquire the reliable channel estimation, whereby the previous noise-reduced PN sequences and a new halting criterion are utilized to improve channel estimation accuracy. Finally, the purification reference signal is obtained via equalization operation. The advantage of the proposed method is that it can obtain superior channel estimation performance and is more efficient compared to existing methods. Numerical and experimental results collected from the DTMB-based PBR system are presented to demonstrate the effectiveness of the proposed method.

Multi-omics analyses reveal relationships among dairy consumption, gut microbiota and cardiometabolic health.

BACKGROUND: Little is known about the interplay among dairy intake, gut microbiota and cardiometabolic health in human prospective cohort studies. METHODS: The present study included 1780 participants from the Guangzhou Nutrition and Health Study. We examined the prospective association between habitual dairy consumption (total dairy, milk, yogurt) and gut microbial composition using linear regression after adjusting for socio-demographic, lifestyle and dietary factors. The cross-sectional association of dairy-associated microbial features with cardiometabolic risk factors was examined with a linear regression model, adjusting for potential confounders. Serum metabolomic profiles were analyzed by partial correlation analysis. FINDINGS: There was a significant overall difference in gut microbial community structure (ß-diversity) comparing the highest with the lowest category for each of total dairy, milk and yogurt (P < 0.05). We observed that dairy-associated microbes and α-diversity indices were inversely associated with blood triglycerides, while positively associated with high-density lipoprotein cholesterol. A follow-up metabolomics analysis revealed the association of targeted serum metabolites with dairy-microbial features and cardiometabolic traits. Specifically, 2-hydroxy-3-methylbutyric acid, 2-hydroxybutyric acid and L-alanine were inversely associated with dairy-microbial score, while positively associated with triglycerides (FDR-corrected P < 0.1). INTERPRETATION: Dairy consumption is associated with the gut microbial composition and a higher α-diversity, which provides new insights into the understanding of dairy-gut microbiota interactions and their relationship with cardiometabolic health. FUNDING: This work was supported by the National Natural Science Foundation of China, Zhejiang Ten-thousand Talents Program, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

Isoflavone biomarkers are inversely associated with atherosclerosis progression in adults: a prospective study.

BACKGROUND: Many studies have examined associations between dietary isoflavones and atherosclerosis, but few used objective biomarkers. OBJECTIVES: We examined the associations of isoflavone biomarkers (primary analyses) and equol production (secondary analyses) with the progression of carotid intima-media thickness (cIMT), and whether inflammation, systolic blood pressure (SBP), blood lipids, and sex hormone-binding globulin (SHBG) mediated these associations, in Chinese adults. METHODS: This 8.8-y prospective study included 2572 subjects (40-75 y old) from the GNHS (Guangzhou Nutrition and Health Study; 2008-2019). The concentrations of daidzein, genistein, and equol were assayed by an HPLC-tandem MS in serum (n = 2572) at baseline and in urine (n = 2220) at 3-y intervals. The cIMT of the common carotid artery (CCA) and bifurcation segment were measured by B-mode ultrasound every 3 y, and the progressions of cIMT ( ∆cIMT) were estimated using the regression method. RESULTS: Multivariable linear mixed-effects models (LMEMs) and ANCOVA revealed that subjects with higher serum isoflavones tended to have lower increases of CCA-cIMT. The mean ± SEM differences in 8.8-y ∆CCA-cIMT between extreme tertiles of serum isoflavones were -17.1 ± 8.4, -20.6 ± 8.3, and -23.3 ± 10.4 µm for daidzein, total isoflavone, and equol (P-trends < 0.05), respectively. LMEMs showed that the estimated yearly changes (95% CIs) (µm/y) in CCA-IMT were -2.0 (-3.8, -0.3), -1.9 (-3.6, -0.1), and -2.1 (-3.8, -0.3) in the highest (compared with the lowest) tertile of daidzein, genistein, and total isoflavones, respectively (P-interaction < 0.05). Path analyses indicated that the serum equol-atherosclerosis association was mediated by increased SHBG and decreased SBP. Similar beneficial associations were observed in the secondary analyses. CONCLUSIONS: Serum isoflavones and equol exposure were associated with reduced cIMT progression, mediated by SHBG and SBP.

Serum isoflavones and lignans and odds of breast cancer in pre- and postmenopausal Chinese women.

OBJECTIVE: Isoflavones and lignans are phytoestrogens present in plant-based foods, which have a potential preventive effect on breast carcinogenesis. The effects of phytoestrogens on breast cancer may differ according to the hormonal environment. This case-control study aimed to investigate the association between serum phytoestrogens and odds of breast cancer among Chinese pre- and postmenopausal women. METHODS: A total of 792 cases and 813 age-matched controls were included. Serum isoflavone (daidzein, genistein, glycitein, equol, and formononetin) and lignan (enterodiol and enterolactone) concentrations were measured using a liquid chromatography-tandem mass spectrometry method. RESULTS: Significant inverse associations were found between serum total soy isoflavone precursors, daidzein, genistein, formononetin, total lignans, enterodiol, enterolactone, and the odds of breast cancer in premenopausal but not postmenopausal women. For premenopausal women, the adjusted odds ratios (95% confidence intervals) for the highest versus the lowest serum concentration groups were 0.60 (0.41-0.87) for total soy isoflavones precursors, 0.64 (0.44-0.93) for daidzein, 0.62 (0.43-0.90) for genistein, 0.49 (0.35-0.68) for formononetin, 0.38 (0.25-0.57) for total lignans, 0.49 (0.33-0.73) for enterodiol, and 0.49 (0.33-0.74) for enterolactone. However, the interaction between serum phytoestrogens and menopausal status on odds of breast cancer was statistically significant only for daidzein. No significant association was found between serum equol or gycitein and the odds of breast cancer among either pre- or postmenopausal women. CONCLUSIONS: Higher levels of certain serum isoflavones and lignans were associated with reduced odds of breast cancer in premenopausal women, but the interaction was statistically significant only for daidzein.

Comprehensive analysis of lncRNAs N6-methyladenosine modification in colorectal cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (M6A) modifications are involved in cancer occurrence and development. METHODS: lncRNA M6A modification in colorectal cancer (CRC) was comprehensively analyzed for the first time. RESULTS: M6A levels of lnRNAs in CRC tissues were higher than those in tumor-adjacent normal tissues. A total of 8,332 M6A peaks were detected in 6,690 lncRNAs in CRC tissues. Approximately 91% of the modified lncRNAs had unique M6A modification peaks. A total of 383 lncRNAs were differentially methylated in CRC, of which 48.24% had a length of 1-1,000 bp. Most of these were located on chromosomes 1, 2, 7, 11, 16 and 19; 42.3% were within a sense-overlapping exon. RNA sequencing identified 163 differentially expressed lncRNAs in CRC. GO and KEGG analyses revealed that genes near differentially-methylated or -expressed lncRNAs were associated with CRC occurrence and development. Methylation was positively correlated with lncRNA expression levels in CRC and tumor-adjacent normal tissues. More unmethylated than M6A methylated lncRNA molecules were detected. A competing endogenous RNA (ceRNA) and lncRNA-mRNA expression-regulation network revealed a regulatory relationship between lncRNAs, microRNAs (miRNAs), and mRNAs. CONCLUSIONS: The findings may help improve our understanding of lncRNA function in colorectal cancer.

Dietary fiber regulates intestinal flora and suppresses liver and systemic inflammation to alleviate liver fibrosis in mice.

OBJECTIVES: Liver fibrosis is a common pathologic process related to chronic liver disease. However, there are currently no effective methods to reverse liver fibrosis. Chronic liver disease is typically associated with a major imbalance in the intestinal flora, and targeting the regulation of the intestinal flora structure may facilitate the prevention and treatment of chronic liver disease. Therefore, in this study, we explored the effects of dietary fiber on the prevention of liver fibrosis in mice. METHODS: C57BL/6J mice were randomly divided into 4 groups: olive oil group (control), fibrosis (CCl4) group, resistant maltodextrin (RM) + CCl4 group, and wheat fiber (WF) + CCl4 group. In the latter 3 groups, liver fibrosis was established by treatment with CCl4. In the RM + CCl4 and WF + CCl4 groups, the mice were treated with soluble dietary fiber (RM) or insoluble dietary fiber (WF) for 3 wk before receiving CCl4. The effects of dietary fiber on various indexes of liver fibrosis in mice induced by CCl4 were observed. RESULTS: The results showed that increasing dietary fiber intake prevented liver fibrosis in mice, reduced serum levels of proinflammatory factors (e.g., tumor necrosis factor-alpha, interleukin [IL] 1-beta and IL-6) and increased IL-10 and interferon-gamma levels. Moreover, increased dietary fiber intake also reduced the infiltration of cluster of differentiation (CD) 3+, 4+, and 8+ T lymphocytes in the liver, regulated the structure of the intestinal flora, and increased the Bacteroidetes/Firmicutes ratio. CONCLUSIONS: Our findings revealed the complex relationships between dietary fiber, intestinal flora, and immunity, and suggested that dietary therapy could alleviate liver fibrosis.

Associations between serum concentration of flavonoids and breast cancer risk among Chinese women.

PURPOSE: In vitro and in vivo studies suggested that flavonols, flavones, flavanones and flavan-3-ols have preventive effects on breast carcinogenesis. Epidemiological evidence about the associations between these flavonoid biomarkers and breast cancer risk is limited. This study aimed to investigate the association between serum concentration of these flavonoids and breast cancer risk among Chinese women. METHODS: This hospital-based case-control study recruited 792 breast cancer cases and 813 age frequency-matched (5-year interval) controls who provided eligible blood samples in Guangdong Province, China. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure flavonoids. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI). RESULTS: Higher concentrations of serum flavonols, isorhamnetin, kaempferol, flavanones and naringenin were significantly associated with lower breast cancer risk, with adjusted ORs (95% CIs) for the highest versus the lowest group of 0.66 (0.49-0.89) for flavonols, 0.52 (0.38-0.70) for isorhamnetin, 0.60 (0.45-0.80) for kaempferol, 0.65 (0.49-0.87) for flavanones and 0.45 (0.34-0.60) for naringenin, respectively. Significant positive associations were observed between serum flavan-3-ols, epigallocatechin, epigallocatechin-3-gallate and breast cancer risk. No significant associations were observed for serum quercetin, flavones, apigenin, luteolin, hesperetin, catechin, epicatechin and epicatechin-3-gallate with overall breast cancer risk. CONCLUSIONS: This study suggested that serum flavonols and flavanones were inversely associated with breast cancer risk and serum flavan-3-ols were positively associated with breast cancer risk. Serum flavones were not associated with overall breast cancer risk. These findings warrant further confirmation in prospective studies.

The Effect of Probiotics Supplementation on Gut Microbiota After Helicobacter pylori Eradication: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Helicobacter pylori eradication therapy may lead to the perturbation of gut microbiota. We aim to investigate the impact of probiotics on eradication rate and gut microbiota during eradication therapy. METHODS: A total of 162 patients receiving bismuth quadruple therapy were enrolled and randomly assigned to groups given probiotics (n = 83) or placebo (n = 79) for 4 weeks. Fecal samples were collected before treatment and 2, 4, 6, and 8 weeks after eradication therapy. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing. RESULTS: The eradication rates in the placebo and probiotics group were 82.43% and 87.01%, respectively (P > 0.05). Compared with baseline, alpha and beta diversity was significantly altered 2 weeks after eradication in both groups, which was restored at week 8. There were no significant differences in diversity between the two groups. H. pylori eradication therapy resulted in enrichment of some detrimental bacteria taxa such as Shigella, Klebsiella, and Streptococcus, while probiotics supplementation could rapidly restore these taxa levels after eradication and increase the taxa of Bacillus and Lactobacillales. Functional analysis revealed that lipopolysaccharide biosynthesis and polymyxin resistance pathways were significantly enriched after eradication, while probiotics supplementation mainly enriched the cofactors and vitamins metabolism pathways. Increased relative abundances of Roseburia and Dialister were associated with the positive eradication outcome. CONCLUSIONS: Probiotics supplementation might help to construct a beneficial profile of gut microbiota after eradication therapy. Specific bacteria taxa are associated with H. pylori eradication outcome. These findings may be of value in rational use of probiotics during H. pylori eradication. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022116.

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies.

BACKGROUND: Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. METHODS: This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008-2013). Fecal samples were collected at follow-up (2015-2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. RESULTS: In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71-0.97). The FMI-fruit association (p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84-0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51-0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13-1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09-1.54), oleylcarnitine (OR 1.77, 95%CI 1.45-2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37-2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33-2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25-1.72) were positively associated with T2D risk. CONCLUSIONS: Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

Potential role of fecal microbiota in patients with constipation.

BACKGROUND: We evaluated the safety and efficacy of fecal microbiota transplantation (FMT) for chronic functional constipation (CFC) ineffectively treated by conventional constipation medication. METHODS: Thirty-four patients with CFC underwent FMT treatment (three rounds, via gastroscopy). Clinical scales, including the Wexner constipation score as the main index of efficiency, were completed at baseline; after each treatment, and at 2 and 3 months of follow up. Secondary evaluation indices included the self-assessment of constipation symptoms, patient assessment constipation quality-of-life questionnaire, Bristol stool form scale, and Zung's self-rating depression and anxiety scales. Gastrointestinal motility, motilin, gastrin, nitric oxide (NO), and 5-hydroxytryptamine (5-HT) were assessed before and after treatment. Intestinal flora changes were assessed by 16S ribosomal ribonucleic acid (rRNA) sequencing. RESULTS: There were no serious adverse reactions. The clinical cure rate was 73.5% (25/34), clinical remission rate was 14.7% (5/34), and the inefficiency rate was 11.8% (4/34). Clinical scale data indicated that the FMT treatment was effective. Furthermore, FMT treatment promoted intestinal peristalsis, increased gastrointestinal motility, and increased serum NO and 5-HT levels. The 16S rRNA sequencing data indicated that high abundances of Bacteroides, Klebsiella, Megamonas, Erysipelotrichaceae and Epulopiscium may be the cause of constipation, and high abundances of Prevotella, Acidaminococcus and Butyricimonas may be the main factors in curing constipation. CONCLUSION: Treatment with FMT regulates the intestinal microflora and changes the abundance of CFC-associated bacterial flora to improve constipation.

Circulating Very-Long-Chain Saturated Fatty Acids Were Inversely Associated with Cardiovascular Health: A Prospective Cohort Study and Meta-Analysis.

Saturated fatty acids with different chain lengths have different biological activities, but little is known about very-long-chain saturated fatty acids (VLCSFAs). This study investigated the associations between the circulating VLCSFAs and cardiovascular health. This community-based cohort study included 2198 adults without carotid artery plaques (CAPs) at baseline. The percentage of baseline erythrocyte VLCSFA (arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)) was measured by gas chromatography. The presence of CAPs was determined at baseline and every 3 years thereafter by ultrasound examination. A meta-analysis was conducted to summarize the pooled associations between circulating VLCSFAs and the risk of cardiovascular diseases (CVDs). During a median of 7.2 years of follow-up, 573 women (35.1%) and 281 men (49.6%) were identified as CAP incident cases. VLCSFAs were inversely related with CAP risk in women (all p-trend <0.05) but not in men. Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CAPs for the highest (vs. lowest) quartile were 0.80 (0.63-1.01) for C20:0, 0.71 (0.56-0.89) for C22:0, 0.75 (0.59-0.94) for C24:0, and 0.69 (0.55-0.87) for total VLCSFAs in women. The pooled HRs (95% CIs) of CVDs for the highest (vs. lowest) circulating VLCSFAs from seven studies including 8592 participants and 3172 CVD events were 0.67 (0.57-0.79) for C20:0, 0.66 (0.48-0.90) for C22:0, and 0.57 (0.42-0.79) for C24:0, respectively. Our findings suggested that circulating VLCSFAs were inversely associated with cardiovascular health.

Association between erythrocyte membrane n-3 and n-6 polyunsaturated fatty acids and carotid atherosclerosis: A prospective study.

BACKGROUND AND AIMS: The relationship of polyunsaturated fatty acids (PUFAs) with cardiovascular risk is still controversial. We aimed to determine whether erythrocyte n-3 and n-6 PUFAs are related to the risk of carotid atherosclerosis. METHODS: From 2008 to 2019, baseline erythrocyte n-3 and n-6 PUFAs were determined in a cohort of 4040 Chinese adults (40-75 ys). The intima-media thickness (IMT) at the common carotid artery (CCA) and bifurcation of the carotid artery (BIF) and carotid plaque were assessed using ultrasonography at baseline and every 3 years. RESULTS: During a median follow-up of 8.8 years, we identified the following newly diagnosed cases: 535 cases of CCAIMT thickening, 654 cases of BIFIMT thickening, and 850 cases of carotid plaque. Higher erythrocyte docosahexaenoic acid (DHA) and arachidonic acid (ARA) and lower gamma-linolenic acid (GLA) were associated with decreased risks of BIFIMT thickening. N-3 eicosatrienoic acid (ETrA), docosapentaenoic acid (DPA), and n-6 dodecylthioacetic acid (DTA) presented a significant beneficial association with carotid IMT thickening in the short-term (2.8 y) follow-up (all p trend <0.02), although the association was attenuated in the relatively long-term (8.8 y) follow-up. In addition, carotid plaque risk was found to be inversely associated with ETrA and DHA but positively associated with alpha-linolenic acid (ALA). N-6 linolenic acid (LA) and eicosadienoic acid (EDA) were not significantly associated with carotid atherosclerosis risk. CONCLUSIONS: Higher erythrocyte very-long-chain n-3 and n-6 PUFAs (especially DHA and ARA) and lower erythrocyte GLA are associated with lower carotid atherosclerosis risk, suggesting potential cardioprotective roles of very-long-chain PUFAs.

Early-Recurrent Overt Hepatic Encephalopathy Is Associated with Reduced Survival in Cirrhotic Patients after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To investigate the role of early overt hepatic encephalopathy (OHE) as a clinical marker of prognosis in cirrhosis with a transjugular intrahepatic portosystemic shunt (TIPS) and to assess the relationship between recurrence of OHE and survival after TIPS. METHODS: From January 2012 to December 2013, a retrospective study of consecutive patients with cirrhosis and a TIPS was performed at a single institution. A total of 304 patients (196 males; mean age, 52 years) were enrolled during the study period. The mean Model for End-Stage Liver Disease (MELD) score was 11.6. Time-dependent Cox regression was applied to estimate the predictive ability of early OHE (within 3 months after TIPS) and the effect of its frequency on survival. RESULTS: During a median follow-up of 28.3 months, 115 patients experienced OHE after the TIPS procedure; of these, 54 had at least 2 OHE episodes. Long-term survival worsened in patients with early OHE (hazard ratio [HR] = 2.75; 95% confidence interval [CI]: 1.75-4.32; P < .001). When early OHE was further divided into early-recurrent and single OHE, death was more common in patients with early-recurrent OHE (P < .001) than in patients with early-single OHE (P = .24). After adjustment by MELD score, ascites, serum albumin, indication for TIPS, and age, patients with early-recurrent OHE had a lower probability of survival (HR = 2.91; 95% CI: 1.04-4.89; P < .001). Furthermore, landmark and propensity score analyses confirmed the predictive value of early-recurrent OHE. CONCLUSIONS: Early recurrence of OHE was associated with an increased risk of mortality for patients with cirrhosis who underwent TIPS.