Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

Glycosidic linkages of fungus polysaccharides influence the anti-inflammatory activity in mice.

INTRODUCTION: Over decades, the source-function relationships of bioactive polysaccharides have been progressively investigated, however, it is still unclear how a defined structure may conduce to the bioactivities of polysaccharides. OBJECTIVES: To explore the structure-function relationship of fungus polysaccharides, we employed a dextran sulfate sodium (DSS)-induced colitis mouse model to compare the anti-inflammatory activity of two fungus polysaccharides from Dictyophora indusiata (DIP) and Tremella fuciformis (TFP), which exhibit distinct glycosidic linkages. METHODS: The structures of DIP and TFP were characterized through molecular weight detection, molecular morphology analysis, methylation analysis, and NMR analysis. Subsequently, we employed a DSS-induced colitis model to assess the anti-inflammatory efficacy of DIP and TFP. The colitis symptoms, histological morphology, intestinal inflammatory cytokines, and the composition and function of gut microbiota before and after polysaccharides treatment in colitis mice were also investigated. RESULTS: DIP, l,3-ß-D-glucan with 1,4-ß and 1,6-ß-D-Glcp as branched chains, exhibited superior therapeutic effect than that of TFP consisted of a linear 1,3-α-D-mannose backbone with D-xylose and L-fucose in the side chains. Both DIP and TFP relieved DSS-induced colitis in a gut microbiota-dependent manner. Furthermore, metagenomics showed that DIP and TFP could partially reverse the bacterial function in colitis mice. Glycoside Hydrolase 1 (GH1) and GH3 were identified as being involved in hydrolyzing the glucose linkages in DIP, while GH92 and GH29 were predicted to be active in cleaving the α-1,3-linked mannose linkages and the glycosidic bonds of L-fucose residues in TFP. CONCLUSION: Our findings highlight the pivotal role of glycosidic linkages in anti-inflammatory activities of fungus polysaccharides and would promote the design and discovery of polysaccharides with designated activity to be used as functional foods and/or therapeutics.

Predictive value of serum fibroblast growth factor 19 and liver stiffness for intestinal failure associated liver disease-cholestasis.

BACKGROUND: Intestinal failure associated liver disease (IFALD)-cholestasis is a common complication of long-term parenteral nutrition (PN) in patients with intestinal failure (IF). The lack of effective early identification indicators often results in poor clinical outcomes. The objective of this study was to evaluate the predictive value of serum FGF19 and liver stiffness in IFALD-cholestasis. METHODS: Eligible adults diagnosed with IF were identified from Jinling Hospital in China. Diagnostic criteria for IFALD-cholestasis: total bilirubin >1 mg/dL and conjugated bilirubin >0.3 mg/dL for ≥6 months. Fasting blood specimens were prospectively collected and serum FGF19 concentrations were determined using ELISA and liver stiffness was measured by Two-dimensional shear wave elastography. Binary logistic regression analysis identified predictors of IFALD-cholestasis. Receiver operating characteristic (ROC) curves and areas under the ROC curves (AUROC) were used to evaluate the accuracy of serum FGF19 and liver stiffness in identifying IFALD-cholestasis. RESULTS: Of 203 study patients with IF, 70 (34.5%) were diagnosed with IFALD-cholestasis. The serum FGF19 levels in those with IFALD-cholestasis were significantly decreased compared with those in patients without, and liver stiffness was significantly increased (p < 0.001). Multivariate logistic regression analyses suggested that intestinal discontinuity, dependence on PN, liver stiffness >6.5 kPa, and serum FGF19 ≤107 pg/mL were independent risk factors for IFALD-cholestasis. The AUROC for serum FGF19 and liver stiffness, which indicate the occurrence of IFALD-cholestasis, were 0.810 and 0.714, respectively. Serum FGF19 had a superior predictive performance than liver stiffness (p < 0.05). CONCLUSION: Both low circulating serum FGF19 concentration and increased liver stiffness are excellent predictors of IFALD-cholestasis, but serum FGF19 is superior to increased liver stiffness in predicting IFALD-cholestasis.

Effects of resistance training on sarcopenia in patients with intestinal failure: A randomized controlled trial.

BACKGROUND: The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of a resistance training program on appendicular skeletal muscle index (ASMI), physical performance, body composition, biochemical parameters, and health-related quality of life (HRQOL) in patients with IF exhibiting sarcopenia. METHODS: A single-center randomized controlled trial was conducted in a Chinese tertiary teaching hospital. Patients with IF exhibiting sarcopenia were randomly assigned to the exercise group or control group. Participants in the exercise group incorporated four sets of resistance training involving the limbs and abdominal and lower back muscles, six times weekly for 4 weeks. The control group received no specific intervention. The primary outcome was the between-group difference in ASMI 4 weeks after intervention. Secondary outcomes included handgrip strength, 6-m gait speed, body composition, biochemical parameters, and HRQOL. RESULTS: A total of 60 participants (control group 30, age 51.2 ± 12.9 years, women 43.3%; exercise group 30, age 53.9 ± 14.5 years, women 56.7%) completed the 4-week intervention trial. For the primary outcome, significant intervention effects were found in ASMI between the exercise group and the control group (mean difference 0.72, 95% CI, 0.56-0.89, P < 0.001). There were notable differences in handgrip strength (mean difference 2.7, 95% CI, 1.7-3.6, P < 0.001), 6-m gait speed (mean difference 0.08, 95% CI, 0.01-0.35, P = 0.034), body composition (including total cell mass, bone mineral content, skeletal muscle mass, lean mass, visceral fat area, total body water, intracellular water, extracellular water, and segmental water-legs), and biochemical parameters (including IGF-1, prealbumin, and hemoglobin) between the two groups (P < 0.05). No significant intervention benefits were observed for other secondary outcomes, including biochemical parameters (including albumin, total bilirubin, etc.) and HRQOL (P > 0.05). CONCLUSIONS: In this randomized clinical trial, we observed that 4 weeks of resistance training was associated with improved ASMI, physical performance, biochemical parameters (including IGF-1, prealbumin, and hemoglobin), and body composition in IF patients with sarcopenia. Resistance training can be recommended as a simple and effective method to improve sarcopenia in patients with IF. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2100051727.

Home nutrition nursing and follow-up pattern for intestinal failure.

BACKGROUND AND OBJECTIVES: To establish and apply the home nutrition care and follow-up management pattern for the treatment of patients with intestinal failure (IF). METHODS AND STUDY DESIGN: This retrospective study analyzed patients with IF who received nutrition nursing and follow-up management at the Clinical Nutrition Treatment Center of Jinling Hospital between January 2018 and April 2022. The changes in nutritional indicators and body compositions of patients before and after standardized management were recorded and compared. RESULTS: A total of 65 patients with IF were enrolled, with a mean age of 52.4±15.8 years and BMI of 17.9±2.7 kg/m2. Compared with before the application of home nutrition nursing and follow-up man-agement, nutritional indicators (Albumin, Prealbumin, and Hemoglobin) were improved significantly in IF patients after the standard management (p<0.05, all). In addition, the body mass index (BMI), fat-free mass index (FFMI), and skeletal muscle mass index (SMI) were also significantly increased after standard management (p<0.05, all). CONCLUSIONS: The establishment and application of home nutrition nursing and follow-up pattern could ensure the nutritional support effect and improve the nutritional status and body composition of patients with IF.

Turmeric-derived nanovesicles as novel nanobiologics for targeted therapy of ulcerative colitis.

Rationale: Ulcerative colitis (UC), a typical kind of inflammatory bowel disease (IBD), is an idiopathic chronic intestinal inflammation. Conventional therapeutic strategies mainly focus on the rebalance of pro-inflammation and anti-inflammation cytokines, whereas targeting damaged intestinal barriers, imbalanced intestinal microbiota and dysregulated mucosal immune responses in UC remain a big challenge. The objective of this study was to develop turmeric-derived nanovesicles (TNVs) for alleviation of colitis and explore the underlying mechanisms. Methods: TNVs were isolated and purified through differential centrifugation. The targeted ability was evaluated on the dextran sulfate sodium (DSS)-induced mouse model by IVIS imaging system. The anti-inflammation efficacy was studied in lipopolysaccharide (LPS)-induced macrophages and DSS-induced acute and chronic colitic mouse model. In addition, the influence of TNVs on the intestinal microbiota was investigated via 16S rRNA microbiome sequence and the condition of macrophage polarization after TNVs treatment was analyzed by flow cytometry. Results: TNVs were isolated and characterized as nano-size spheroids. The IVIS imaging experiment indicated that orally administrated TNVs could accumulate in the inflamed colon sites and exhibited superior anti-inflammatory activity both in vitro and in vivo. The 16S rRNA sequencing suggested the important role of TNVs in the regulation of gut microbiota. Further, TNVs could promote the transformation of M1 phenotype to M2 macrophages and restore the damaged intestinal epithelium barrier to exert the anti-colitis efficacy. Conclusion: Collectively, oral administration of TNVs exhibited excellent anti-inflammatory efficacy through restoring the damaged intestinal barrier, regulating the gut microbiota and reshaping the macrophage phenotype. This study sheds light on the application of natural exosome-like nanovesicles for the treatment of UC.

Prevalence, Risk Factors, and Complications of Cholelithiasis in Adults With Short Bowel Syndrome: A Longitudinal Cohort Study.

Background: Patients with short bowel syndrome (SBS) are at a high risk of cholestasis or cholelithiasis. This study aimed to determine the incidence, risk factors, and clinical consequences of cholelithiasis in adults with SBS over an extended period. Methods: All eligible adults diagnosed with SBS and admitted to a tertiary hospital center between January 2010 and December 2019 were retrospectively identified from the hospital records database. Kaplan-Meier analysis was used to estimate the cumulative incidence of SBS during the 10-year period. For assessment the risk factors for cholelithiasis, we used multivariate Cox proportional hazards model with estimation of hazard ratio (HR) with 95% confidence intervals (95 %CI). Results: This study enrolled 345 eligible patients with SBS. Kaplan-Meier analysis revealed that 72 patients (20.9%) developed cholelithiasis during the 10-year observation period. In multivariate analyses using the Cox proportional hazard model revealed that the remnant jejunum (HR = 2.163; 95% confidence interval [CI]: 1.156-4.047, p = 0.016) and parenteral nutrition dependence (HR = 1.783; 95% CI: 1.077-2.952, p = 0.025) were independent risk factors for cholelithiasis in adults with SBS. Twenty-eight patients developed symptoms and/or complications in the cholelithiasis group. Proportions of acute cholecystitis or cholangitis and acute pancreatitis were significantly increased in the cholelithiasis group compared with the non-cholelithiasis group (31.9 vs. 7.7%, p < 0.01; and 6.9 vs. 1.1%, p = 0.003, respectively). Conclusion: Because of the adverse clinical consequences of cholelithiasis, adult patients with SBS should be closely monitored, and preventive interventions should be considered. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04867538.

The dietary supplement Rhodiola crenulata extract alleviates dextran sulfate sodium-induced colitis in mice through anti-inflammation, mediating gut barrier integrity and reshaping the gut microbiome.

Rhodiola species are edible medicinal plants, which have been traditionally used in both Asia and Europe as an adaptogen, a tonic, an anti-depressant and anti-inflammatory supplement. However, whether it presents a therapeutic effect on colitis or not remains unknown. The aim of this study is to investigate the protective effect of a Rhodiola crenulata extract (RCE) on mice with DSS-induced colitis. RCE significantly alleviated the pathological abnormalities in colitic mice, including the correspondingly increased colon length, ameliorated colonic injury and reduced pro-inflammatory factors. The protective effect was similar to that of the positive control, 5-aminosalicylic acid. The DSS-induced epithelial apoptosis and maintained intestinal barrier function were attenuated by RCE through the upregulation of the level of tight junction proteins such as ZO-1 and occludin. Notably, RCE prevented gut dysbiosis in colitic mice by restoring the microbial richness and diversity, and decreasing the abundance of Proteobacteria phylum and opportunistic pathogenic Parasutterella and Staphylococcus, as well as increasing the abundance of beneficial microbes in Lactobacillus and Bifidobacterium, which were closely correlated with its protective effect against colitis. Meanwhile, chemical characterization of RCE was performed by UPLC-HR-MS to explain its material basis. A total of 63 compounds were identified, while the content of two bioactive ingredients (salidroside, 1.81%; rosavin, 0.034%) was determined.

Computer-aided search for a cold-active cellobiose 2-epimerase.

Cellobiose 2-epimerase (CE) is a promising industrial enzyme that can catalyze bioconversion of lactose to its high-value derivatives, namely epilactose and lactulose. A need exists in the dairy industry to catalyze lactose bioconversions at low temperatures to avoid microbial growth. We focused on the discovery of cold-active CE in this study. A genome mining method based on computational prediction was used to screen the potential genes encoding cold-active enzymes. The CE-encoding gene from Roseburia intestinalis, with a predicted high structural flexibility, was expressed heterologously in Escherichia coli. The catalytic property of the recombinant enzyme was extensively studied. The optimum temperature and pH of the enzyme were 45°C and 7.0, respectively. The specific activity of this enzyme to catalyze conversion of lactose to epilactose was measured to be 77.3 ± 1.6 U/mg. The kinetic parameters, including turnover number (kcat), Michaelis constant (Km), and catalytic efficiency (kcat/Km) using lactose as a substrate were 117.0 ± 7.7 s-1, 429.9 ± 57.3 mM, and 0.27 mM-1s-1, respectively. In situ production of epilactose was carried out at 8°C: 20.9% of 68.4 g/L lactose was converted into epilactose in 4 h using 0.02 mg/mL (1.5 U/mL, measured at 45°C) of recombinant enzyme. The enzyme discovered by this in silico method is suitable for low-temperature applications.

Ultrasensitive all-fiber inline Fabry-Perot strain sensors for aerodynamic measurements in hypersonic flows.

This work proposes an ultrasensitive, temperature-insensitive, all-fiber inline Fabry-Perot (FP) strain sensor for aerodynamic coefficients measurements of a hypervelocity ballistic correlation model 2 in a Φ1 hypersonic wind tunnel. The FP sensors fabricated using 157 nm laser micromachining system are structurally simple, small-sized, and high-temperature resistance. 16 FP sensors are installed on a six-force balance, which is mounted inside the model, to sense the aerodynamic forces and moments of the model, and then the model's aerodynamic coefficients are calculated based on aerodynamic theory according to the test data. A new temperature-compensated method is proposed to improve measurement accuracy of aerodynamic coefficients via eliminating temperature-induced measurement errors. Experimental results show, at high temperatures, the FP sensors based on the balance (FP balance) exhibits a high-repeatability precision of the aerodynamic coefficients measurement of less than 1%, and match well with the results of the traditional method using foil-resistive strain sensors. This enhanced-sensitivity FP sensor is currently the most promising alternative to foil-resistive strain sensors for aerodynamic tests among kinds of fiber-optic strain sensors to the best of our knowledge. The FP balance satisfies the requirements of practical application of aerodynamic characteristic tests, and opens up another test system of the field.

Semi-rational design and molecular dynamics simulations study of the thermostability enhancement of cellobiose 2-epimerases.

Directed evolution using random mutation in vast sequence space leads to the low probability of obtaining target proteins. Emerging engineering strategies with computational tools are developed for more trustable outcomes. We used some semi-rational design methods to modify an industrial enzyme, namely cellobiose 2-epimerase (CE). A mutant was selected for its better thermostability and isomerization activity. The tradeoffs between thermostability, epimerization activity and isomerization activity of the CE mutants were different. To investigate the computational prediction performance of protein stability upon point mutations, molecular dynamics (MD) simulation analyses were conducted. The root mean square deviation (RMSD) and hydrogen bond analyses reproduced the correct trends in stability changes of the wild-type and mutated CEs with relatively high accuracy (correlation coefficients r ~ 0.5-0.8). The simulation temperature and time are important factors that influence the prediction performance. Our result shows that thermostability predictors calculated from MD simulation do better in predicting the thermostability changes of the mutated enzymes than the predictors using static-state information of the enzymes.

Current methods and applications in computational protein design for food industry.

Computational tools for enzyme engineering can readily be used in a broad range of food industrial applications. However, there are too many choices when the enzymologists try to solve their own problems computationally, especially when their studies need to be carried out with a combination of tools. The correct choice of methods requires a broad understanding of the knowledge framework. Therefore, we present a comprehensive overview of the current computational tools and basic principles for enzyme design. The tools can be classified into several groups, including bioinformatics approaches and the calculation methods based on static systems and dynamics systems. In addition, we also provide some successful examples in the food industrial applications to show that the modern tools can dramatically reduce the experimental effort and can help us better understand the catalytic mechanism of food enzymes.

Simulation-guided enzyme discovery: A new microbial source of cellobiose 2-epimerase.

Cellobiose 2-epimerase (CE) is a promising industrial enzyme that can be utilized in the dairy industry. More thermostable CEs from different microorganisms are still needed for a higher lactulose productivity. This study demonstrated the feasibility to use molecular dynamics (MD) simulation as the preliminary computational filter for thermostable enzymes screening. Sequence information of eleven uncharacterized CEs were chosen to be analyzed by MD simulations. The CE from Dictyoglomus thermophilum (Dith-CE) was determined experimentally to be one of the most thermostable CEs with the highest epimerization (160 ±â€¯6.5 U mg-1) and isomerization activities (3.52 ±â€¯0.23 U mg-1) among all the reported CEs. This enzyme shows the highest isomerization activity at 85 °C and pH 7.0. The kinetic parameters (kcat and Km) of isomerization activity of this CE are 3.98 ±â€¯0.3 s-1 and 235.2 ±â€¯11.2 mM, respectively. These results suggest that the CE from Dith-CE is a promising lactulose-producing enzyme.

Temperature-insensitive fiber-optic tip sensors array based on OCMR for multipoint refractive index measurement.

A temperature-insensitive fiber-optic tip sensors array is proposed for multipoint refractive index measurement using optical carrier based on microwave reflection (OCMR). The tip sensors array is made of a series of cleaved fiber end-faces and is spatially multiplexed by physically connecting with a fiber-optic splitter with different lengths of short delay fiber. A sensors array with eight sensing tips is demonstrated for multipoint refractive index measurement. Experimental results show that it can offer a high refractive-index resolution of 3.60 × 10-6 RIU and a low temperature-refractive index cross sensitivity of 3.74 × 10-7 RIU/°C. Such a sensors array not only possesses excellent sensing performances, but also can be integrated into a chip for biochemical sensing applications.

An overview on biological production of functional lactose derivatives.

Lactose is a natural disaccharide obtained from the milk of most mammals and a waste product of cheese and casein manufacturing. Over the past decades, lactose in whey has increasingly been promoted as an important resource, and an increasing number of significant advances have been made to investigate its healthy and functional properties. Lactose can be biotransformed into many kinds of derivatives, including galacto-oligosaccharides, epilactose, lactulose, lactosucrose, and D-tagatose. Biological efficiency and safety are critical for the enzymatic production of lactose derivatives from lactose. These lactose derivatives show a range of prominent physiological features and effects, such as prebiotic properties, indigestibility, and obesity prevention, which can be utilized in the pharmaceutical, health, and food industries. In this review, we present the properties and physiological effects of lactose derivatives, detailing their biological production by various enzymes and their applications in dairy products, especially directly in the milk industry.

lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1.

BACKGROUND/AIMS: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). METHODS: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. RESULTS: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. CONCLUSION: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.