The protective effect of teprenone in TNBS-induced ulcerative colitis rats by modulating the gut microbiota and reducing inflammatory response.

OBJECTIVE: Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This in vitro and in vivo study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms. METHODS: Human intestinal epithelial cells (Caco-2 cells) serve as the in vitro experimental model. Lipopolysaccharide (LPS, 1 µg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the in vivo assay. RESULTS: Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 µg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, Fusobacterium, Escherichia coli, Porphyromonas gingivalis elevation, and Mogibacterium timidum decline in UC rats were inhibited by teprenone. CONCLUSION: Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.

Long Non-Coding RNA (lncRNA) BMP/OP-Responsive Gene (BORG) Promotes Development of Chemoresistance of Colorectal Cancer Cells to Carboplatin.

BACKGROUND The function of long non-coding RNA (lncRNA) BMP/OP-responsive gene (BORG) has only been studied in breast cancer. We analyzed the role of BORG in colorectal cancer (CRC). MATERIAL AND METHODS BORG in CRC tissues and non-cancer tissues from 66 CRC patients was detected by performing quantitative reverse-transcription PCR (RT-qPCR). BORG in plasma of CRC patients was detected at 3 times-points: before treatment and at 3 and 6 months after treatment. p53 expression in tumor tissues was also detected by RT-qPCR. QPCR was performed to confirm the overexpression of p53 in cells of both CRC cell lines. RESULTS We found that BORG expression was upregulated in CRC tissues and was inversely correlated with p53. With application of carboplatin-based treatment, the expression level of BORG was further upregulated. In CRC cells, carboplatin upregulated the expression of BORG and BORG negatively regulated p53. Under carboplatin treatment, BORG positively regulated the viability of CRC cells. In addition, p53 overexpression attenuated the effects of BORG overexpression. CONCLUSIONS BORG promotes the development of chemoresistance of CRC cells to carboplatin.

Effects of flaxseed supplementation on functional constipation and quality of life in a Chinese population: A randomized trial.

BACKGROUND AND OBJECTIVES: This prospective, randomized, controlled study aimed to evaluate the effects of flaxseed supplementation on functional constipation and quality of life in adult men and women in China. METHODS AND STUDY DESIGN: 90 subjects with functional constipation diagnosed by the Rome IV criteria were enrolled. Subjects were randomly assigned to receive either 50 g/day flaxseed flour with meals (n=60) or 15 mL/day of a lactulose solution on an empty stomach (n=30) every morning for 4 weeks. Wexner constipation scores, stool consistency according to the Bristol Stool Form Scale, and bowel habits (frequency of bowel movements/week, the time spent on defecation) were the primary outcomes. The change in Patient Assessment of Constipation Quality of Life score was the secondary outcome. RESULTS: After 4 weeks, the bowel habits in both groups were significantly improved. The median Wexner constipation score decreased from 14 to 6.5 in the flaxseed group (p<0.001) and from 15 to 9 in the lactulose group (p<0.001). The median defecation frequency per week increased significantly (2 to 7 for flaxseed and 2 to 6 for lactulose, p<0.001 for both groups). The Patient Assessment of Constipation Quality of Life score decreased significantly (-1.34 and -0.66 for flaxseed and lactulose, respectively; p<0.001 for both groups). CONCLUSIONS: Flaxseed flour is somewhat more effective at increasing defecation frequency than lactulose, improving bowel movements and promoting life quality of subjects with chronic functional constipation in the Chinese population.

Continuous subcutaneous insulin infusion combined with liraglutide reduced glycemic variability and oxidative stress in type 2 diabetes mellitus: a study based on the flash glucose monitoring system.

We aimed to explore the use of the flash glucose monitoring (FGM) system in hospitalized newly diagnosed type 2 diabetes mellitus (T2DM) patients and to evaluate a new combination therapy of continuous subcutaneous insulin infusion (CSII) with or without liraglutide. This was an open-label, randomized study that was conducted in 60 newly diagnosed T2DM patients. The patients were randomized to receive either CSII (n = 30) or CSII + liraglutide (n = 30). The FGM system was used to assess the glycemic control and glycemic variability (GV) indices for 2 weeks. Mean blood glucose concentration (MBG), estimated hemoglobin A1c (HbA1c), and measures of GV, including the standard deviation of the mean glucose (SD), coefficient of variation (CV), interquartile range (IQR), mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE), and mean of daily difference (MODD) were compared between the two groups. Two oxidative stress biomarkers, 4-hydroxynonenal (4-HNE) and 8-hydroxydeoxyguanosine (8-OHdG), were measured before and after treatment. The estimated HbA1c and MBG decreased in both groups, especially the CSII + liraglutide group. SD, IQR, LAGE, and MODD were significantly lower in the CSII + liraglutide group than in the CSII group (all p < 0.05); there was no difference in CV or MAGE (p > 0.05). Similarly, the 4-HNE and 8-OHdG levels were significantly lower in the CSII + liraglutide group (p < 0.05). Our findings suggest that CSII with liraglutide was superior to CSII monotherapy in improving glycemic control and glycemic variability and in decreasing oxidative stress markers. Flash glucose monitoring can successfully provide ambulatory glucose profile data in the real world.

Role of sclerostin and dkk1 in bone remodeling in type 2 diabetic patients.

PURPOSE: This study aimed to investigate the role of sclerostin and dkk1 in the bone metabolism of type 2 diabetic patients. METHODS: This cross-sectional study included 95 inpatients with type 2 diabetes mellitus. We divided the patients into three groups (i.e., the normal bone mineral density (BMD) group, osteopenia group and osteoporosis group) based on their different BMD levels and measured the serum levels of sclerostin, dkk1, 25-hydroxyvitamin D3 (25OHD3), bone turnover markers and other biochemical data in each group. RESULTS: Significantly increased levels of serum sclerostin and dkk1 were found in the osteoporosis group, even when the male and female cohorts were considered separately. Ordinal logistic regression analysis suggested that the levels of serum sclerostin were independently associated with the presence of osteopenia and osteoporosis after adjusting for age, gender and 25OHD3 (sclerostin: OR = 1.02, p = 0.001). The areal BMDs were negatively correlated with the levels of serum sclerostin and dkk1 and positively correlated with 25OHD3. In addition, age, glycosylated hemoglobin and serum sclerostin levels were predictors for N-terminal propeptide of type 1 procollagen and serum dkk1 levels were the only predictors for crosslinked carboxyterminal telopeptide in type 1 collagen. CONCLUSIONS: The sclerostin and dkk1 levels increased in conjunction with the reduction of BMD, confirming that the Wnts, inhibited by sclerostin and dkk1, were potentially responsible for bone fragility in type 2 diabetes patients with osteoporosis. Note that the serum sclerostin levels were predictors for bone formation, while the DKK1 levels predicted bone resorption.

Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling.

Deregulation of Toll-like receptor 4 (TLR4) is closely associated with the progression of various types of cancers, but its role in pancreatic carcinogenesis is unclear. This study aimed to investigate the role of TLR4 in the angiogenesis of pancreatic cancer and the underlying molecular mechanisms. The culture supernatant (conditioned medium) of PANC-1 cells after appropriate treatment was used for the treatment of HUVECs. The proliferation, migration and tube formation of HUVECs were assessed by MTT, Transwell and Matrigel, respectively. In pancreatic cancer tissues, TLR4, VEGF and CD31 were upregulated as determined by immunohistochemistry and the expression of TLR4 and VEGF was positively correlated with microvessel density as detected by CD31 staining. Activation of TLR4 signaling by LPS in PANC-1 cells resulted in increased VEGF and phosphorylation of AKT, which were abolished by TLR4 silencing with siRNA and PI3K/AKT signaling inhibitor LY294002. The conditioned medium from PANC-1 cells treated with LY294002 or transfected with TRL4 siRNA reduced the proliferation, migration and tube formation of HUVECs. In contrast, the conditioned medium from PANC-1 cells treated with LPS stimulated the proliferation, migration and tube formation of HUVECs, which was however significantly inhibited by pretreatment of PANC-1 cells with LY294002 or transfection with TRL4 siRNA. Our findings suggest TLR4 may promote angiogenesis in pancreatic cancer by activating the PI3K/AKT signaling pathway to induce VEGF expression.

SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma.

Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1) has been implicated in tumor initiation, formation, and progression of various cancers, yet its role in hilar cholangiocarcinoma remains largely uncharacterized. In the present study, tissue microarrays containing resected hilar cholangiocarcinoma specimens from 92 patients were used to evaluate the expression of SPARCL1 protein by immunohistochemistry (IHC). In vitro assays were used to determine the effect of SPARCL1 overexpression on cell growth and migration. Loss of SPARCL1 expression was observed in 46 (50.0 %) of the 92 primary tumors. SPARCL1 expression is inversely associated with poorly or undifferentiation specimens (P = 0.030) in addition to lymph node metastasis (P = 0.047). Survival analysis demonstrated that SPARCL1 is an independent factor in predicting the outcome of patients with hilar cholangiocarcinoma. SPARCL1 overexpression suppressed tumor cell migration in vitro by inhibiting MMP-9, MMP-2, Vimentin, and Fibronectin expression, whereas did not inhibit cell proliferation in vitro. Our results suggest that loss of SPARCL1 is involved in the tumorigenesis of hilar cholangiocarcinoma and may serve as a novel molecular biomarker for patients' outcome.

Evaluation of the effectiveness of esomeprazole treatment strategies in the management of patients with gastroesophageal reflux disease symptoms: a meta-analysis.

Here we aimed to evaluate the effectiveness of esomeprazole treatment strategies comparing with other proton pump inhibitors (PPI) in clinical practice for six months in the management of patients with symptomatic gastroesophageal reflux disease (GERD). An extensive search of the literature focusing on PPI therapeutic evaluation was performed up to December 2014. Risk ratio (RR) with its corresponding 95% confidence intervals (CIs) in each study was chosen as the effect size. Cochrane's Q statistic and I2 test were both conducted to evaluate heterogeneity across individual studies. Meta-regression was conducted to explore the source of heterogeneity and sensitive analysis was performed to assess the risk bias for the meta-analysis. Totally, eleven trials with high quality enrolled in the meta-analysis. Esomeprazole therapy (20 mg daily) had lower relapse rates than other drugs during six months maintenance treatment (RR = 0.67; 95% CI: 0.55-0.83). Heartburn (RR = 0.72; 95% CI: 0.57-0.92) and epigastric pain (RR = 0.82, 95% Cl: 0.70-0.96) were less likely to happen after esomeprazole treatment, and no significant advantage was found on acid regurgitation and dysphagia. Moreover, lower risk for serious adverse events was observed after esomeprazole therapy (RR = 1.40, 95% CI: 1.04-1.88). Blind method or difference controlled drugs did not influence heterogeneity across studies. Moreover, the conclusion on acid regurgitation, abdominal pain and dysphagia might be unstable. In GERD patients, esomeprazole 20 mg daily is more effective than other PPIs regarding relapse rates, symptoms of epigastric pain and heartburn, and serious adverse events.

Microbial Disruptions in Inflammatory Bowel Disease: A Comparative Analysis.

Objective: The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD. Methods: Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn's disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis. Results: There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly. Conclusion: There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.

IGF1 promotes osteogenic differentiation of mesenchymal stem cells derived from rat bone marrow by increasing TAZ expression.

Whether insulin-like growth factor 1 (IGF1) inhibits or promotes the osteogenic differentiation in vitro remains controversial. Moreover, the biological mechanisms and signaling pathways by which IGF1 affects osteogenic differentiation remain obscure. Transcriptional coactivator with PDZ-binding motif (TAZ) plays a vital role in the osteogenic differentiation of mesenchymal stem cells (MSCs), and strongly activates runt related transcription factor 2 (RUNX2)-driven genes during the terminal osteogenic differentiation. In the present study, we found that IGF1 increased the ALP activities and calcium depositions of MSCs derived from rat bone marrow dose-dependently, with a peak at 100-200ng/ml. IGF1 increased TAZ and RUNX2 expression mainly at the early stage of osteogenic differentiation, but increased OCN expression at the late stage. Our data further demonstrated that down-regulation of TAZ expression by siRNA inhibited the IGF1 induced increase in osteogenic differentiation. Moreover, UO126 (the MEK-ERK inhibitor), not LY294002 (the PI3K-Akt inhibitor), inhibited the IGF1 induced increase in TAZ expression. Taken together, we provide evidence to demonstrate that IGF1 promotes the osteogenic differentiation of rat MSCs by increasing TAZ expression, and that the increased TAZ expression induced by IGF1 is mostly mediated by the MEK-ERK pathway.

Triptolide induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells by downregulating COX-2 and VEGF.

Triptolide (TPL) inhibits the growth and proliferation of a wide range of human cancer cells, but the underlying mechanism is largely unknown. Here, we report that TPL induces apoptosis and inhibits proliferation of PANC-1 pancreatic cancer cells by downregulating cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). Cell viability and apoptosis were measured by MTT assay and flow cytometry. Real-time PCR and Western blot were used to examine the expression of COX-2 and VEGF. The Matrigel angiogenesis and Transwell migration were employed to assess tube formation and cell migration. Pancreatic cancer mouse xenografts were established to investigate the in vivo antitumor effects of TPL. TUNEL staining and immunohistochemistry were used to detect the apoptosis rate and protein expression in tumor tissues. TPL inhibited the proliferation of pancreatic cancer cells in a time and concentration-dependent manner and decreased the expression of COX-2 and VEGF in vitro. Furthermore, medium from TPL-treated PANC-1 cells inhibited the proliferation, migration, and tube formation of HUVECs. TPL significantly reduced the growth of pancreatic cancer mouse xenografts, accompanied by an induction of apoptosis, inhibition of angiogenesis, and reduction of COX-2 and VEGF. Our data indicate that suppressing the expression of COX-2 and VEGF may be one of the molecular mechanisms by which TPL induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells.

Intestinal flora in the constipation patients before versus after lactulose intervention.

This study aimed to investigate the characteristics of intestinal flora in patients with chronic functional constipation before and after lactulose intervention. Twenty-nine patients with constipation in the treatment group received oral lactulose (15 mL/d) for a month. Twenty healthy subjects served as controls. Stool specimens were collected before and after lactulose treatment. Fecal bacteria were examined by 16SrRNA gene sequencing and bioinformatics analysis. After lactulose treatment, most bacteria in the constipation group, including Bifidobacteria, Bacillus cereus, Prevotella, Bacillus, Anaerostipes, Oribacterium, and Mogibacterium increased as compared to those in the healthy control group. Anaerotruncus declined in the healthy control group after lactulose treatment. Our study shows lactulose can increase the abundance of probiotics, optimize the intestinal microenvironment, and alleviate constipation.

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.

Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.

Influence of Flax Seeds on the Gut Microbiota of Elderly Patients with Constipation.

Purpose: This study was to explore the influence of flax seeds on the gut microbiota of elderly patients with functional constipation. Patients and Methods: Sixty elderly patients (68.68±8.73 years) with functional constipation were recruited between January 2018 and March 2018. They received oral flax seeds (50 g/d) for one month. Bowel habits and adverse events were recorded before and after treatment. Fresh stool was collected before and after treatment and the amplification product of 16S rRNA V5 region was sequenced using the next-generation sequencing technique on the Ion Torrent PGM platform. The gut microbiota were analyzed before and after flax seeds treatment in the same subject. Results: Flax-seed treatment significantly increased the frequency of defecation and decreased abdominal distension in elderly patients with chronic constipation. The majority of gut bacteria belonged to the phyla of Firmicutes, Bacteroidetes, and Proteobacteria, accounting for 98.71%. After flax seeds treatment, the diversity of bacterial clusters significantly increased with increases of Roseburia_hominis, Pseudomonas_azotoformans, uncultured_Clostridiales_bacterium, Blautia_obeum, Ruminococcus_sp._16442, Pyramidobacter_piscolens, Acinetobacter_lwoffii, Prevotella_melaninogenica. The abundance of Blautia in patients with chronic constipation was significantly lower than healthy controls, while Blautia_obeum increased significantly after flax seed treatment. Blautia_obeum might be the predominant genus accounting for the therapeutic effect of flax seeds. Conclusion: Flax seeds may improve the defecation in elderly patients with chronic constipation and change intestinal microecological structure. Thus, flax seeds may serve as an effective diet supplement in the management of chronic constipation.

[Effect of the Wnt/LRP5/ß-catenin signaling pathway on the pathogenesis of postmenopausal osteoporosis].

OBJECTIVE: To investigate the role of the Wnt/LRP5/ß-catenin signaling pathway in the pathogenesis of postmenopausal osteoporosis. METHODS: Fifty female Wistar rats aged 6-month-old, were randomly divided into control group (NS, n = 24) and ovariectomized group (NOVX, n = 26), NOVX underwent bilateral ovariectomy. At 0, 4 and 8 weeks, all of rats were measured blood estrogen (E(2)) and bone mineral density (BMD), 4 and 8 weeks, low density lipoprotein receptor-related protein 5 (LRP5), ß-catenin and Runx2 mRNA in bone were measured respectively by reverse transcription (RT)-PCR. RESULTS: In 4 and 8 weeks, compared with NS which had (117 ± 29) and (114 ± 15) pmol/L in E(2) level, (0.098 ± 0.016) and (0.095 ± 0.028) g/cm(2) in BMD, NOVX had significantly decreased to (92 ± 15) and (95 ± 22) pmol/L in E(2) level (P < 0.05), (0.076 ± 0.016) and (0.052 ± 0.013) g/cm(2) in BMD values (P < 0.01). And bone tissue LRP5, ß-catenin and Runx2 mRNA expression was 1.02 ± 0.06, 1.04 ± 0.05, 1.07 ± 0.21 in NS, NOVX was significantly reduced to 0.97 ± 0.04, 0.58 ± 0.05, 0.86 ± 0.03 (P < 0.05). CONCLUSION: Wnt/LRP5/ß-catenin signaling pathway may be important in the pathogenesis of postmenopausal osteoporosis.

Generation and characterization of isolates of Peronophythora litchii resistant to carboxylic acid amide fungicides.

Four isolates of Peronophythora litchii with resistance to carboxylic acid amide (CAA) fungicides were selected on fungicide-amended agar. These isolates had various levels of resistance, as evidenced by their resistance factor (RF), which is the 50% effective concentration (EC(50)) value of a particular isolate divided by that of the wild-type parent. RF values to dimethomorph for the four isolates were 15, 24, 141, and >1,500. Resistance was stable for two isolates, while the EC(50) values decreased for the other two after repeated subculturing on fungicide-free medium. Cross-resistance occurred with all CAAs tested here (dimethomorph, mandipropamid, flumorph, and pyrimorph), but not with strobilurins (azoxystrobin and famoxadone) or other fungicides (metalaxyl, cymoxanil, and mancozeb). Studies on fitness parameters (mycelial growth, sporulation, spore germination, zoospore formation, aggressiveness, and temperature tolerance) in the parent wild-type and resistant isolates demonstrated that penalties in different parameters may be associated with CAA resistance, depending on the isolate. These studies show that Peronophythora litchii is able to express CAA resistance under laboratory conditions but it is not known if resistant strains could become established in the field and sensitivity monitoring studies are recommended.

Use of flash glucose-sensing technology in patients with type 2 diabetes treated with liraglutide combined with CSII: a pilot study.

Glycemic variability (GV) may be linked to the development of diabetic complications by inducing inflammation, oxidative stress, and endothelial dysfunction. Flash glucose monitoring (FGM) provides a novel method of continuously monitoring interstitial glucose levels for up to 14 days. This study randomly assigned poorly controlled type 2 diabetes mellitus patients treated with metformin and multiple daily injections of insulin (n=60) to either continuous subcutaneous insulin infusion (CSII) treatment or CSII in combination with liraglutide (CSII+Lira) treatment for 14 days during hospitalization. GV was assessed using a FGM system; weight and cardiometabolic biomarkers were also evaluated. The coefficient of variation was significantly reduced in the CSII+Lira group (P<0.001), while no significant change was observed in the CSII group. The changes differed significantly between the two groups in mean amplitude of glycemic excursions (P=0.004), standard deviation (P=0.006), and the percentage of time in the target range (4-10 mmol/L, P=0.005 and >10 mmol/L, P=0.028). The changes in mean of daily differences, interquartile range, and percentage of time in hypoglycemia (<3.3 mmol/L) and hyperglycemia (>13.9 mmol/L) identified by FGM showed no difference. Treatment with liraglutide increased serum adiponectin [33.5 (3.5, 47.7) pg/mL, P=0.003] and heme oxygenase-1 levels [0.4 (-0.0, 1.8) ng/mL, P=0.001] and reduced serum leptin levels [-2.8 (3.9) pg/mL, P<0.001]. Adding the glucagon-like peptide-1 analog liraglutide improved GV, weight, and some cardiometabolic risk markers. The FGM system is, therefore, shown to be a novel and useful method for glucose monitoring.

Author Correction: Effects of rainfall manipulation and nitrogen addition on plant biomass allocation in a semiarid sandy grassland.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effects of rainfall manipulation and nitrogen addition on plant biomass allocation in a semiarid sandy grassland.

Extreme climate events and nitrogen (N) deposition are increasingly affecting the structure and function of terrestrial ecosystems. However, the response of plant biomass to variations to these global change drivers is still unclear in semi-arid regions, especially in degraded sandy grasslands. In this study, a manipulative field experiment run over two years (from 2017 to 2018) was conducted to examine the effect of rainfall alteration and nitrogen addition on biomass allocation of annuals and perennial plants in Horqin sandy grassland, Northern China. Our experiment simulated extreme rainfall and extreme drought (a 60% reduction or increment in the growing season rainfall with respect to a control background) and N addition (20 g/m2) during the growing seasons. We found that the sufficient rainfall during late July and August compensates for biomass losses caused by insufficient water in May and June. When rainfall distribution is relatively uniform during the growing season, extreme rainfall increased aboveground biomass (AGB) and belowground biomass (BGB) of annuals, while extreme drought reduced AGB and BGB of perennials. Rainfall alteration had no significant impacts on the root-shoot ratio (R/S) of sandy grassland plants, while N addition reduced R/S of grassland species when there was sufficient rainfall in the early growing season. The biomass of annuals was more sensitive to rainfall alteration and nitrogen addition than the biomass of perennials. Our findings emphasize the importance of monthly rainfall distribution patterns during the growing season, which not only directly affect the growth and development of grassland plants, but also affect the nitrogen availability of grassland plants.

The composition of intestinal microbiota and its association with functional constipation of the elderly patients.

Aim: To identify intestinal microbiota compositions in elderly functional constipation (FC) patients. Materials & methods: Fecal samples from 61 FC patients and 48 healthy age-matched volunteers were analyzed through 16S rRNA gene sequencing. Results: The intestinal microbiota compositions of FC patients were significantly different from healthy controls. Additionally, the species diversity of healthy controls was greater than that of FC patients. Indeed, the abundance of Firmicutes and Proteobacteria was significantly decreased, whereas that of Bacteroides, Prevotella, Lactococcus, Ruminococcus and Butyricimonas was remarkably increased in FC patients. Conclusion: Elderly FC patients appear to have a unique intestinal microbiota profile. Our findings should provide insight regarding the pathogenic mechanism of FC and evidence for exploring new therapeutic strategies in elderly FC patients.