Junli Ren

The viable bacterial strains in conventional yogurt are intolerant to bile acid, which consequently cannot survive the conditions and their beneficial bioactivities are thus lost. We have previously shown that Lactobacillus casei Q14 ( Lac-Q14), a probiotic, has the potential to alleviate diabetes in rats. Herein, we used Lac-Q14 as the starter culture to ferment yogurt and explore the mechanisms of the bioactivity in diabetic rats. The results showed that Lac-Q14 yogurt improved blood glucose and insulin level, lowered gene expression of critical enzymes involved in liver gluconeogenesis. Pyrosequencing showed an obvious change in the composition of intestinal microbiota in Lac-Q14 yogurt treated rats. The abundance of 21 genera differed significantly between the Lac-Q14 yogurt group and diabetes group. Quite a few short-chain fatty acid (SCFA)-producing bacteria were selectively enriched, along with increased concentrations of SCFA and downstream Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY) secretion.

BACKGROUND: Stress hyperglycemia ratio (SHR), calculated as glucose/glycated hemoglobin, has recently been developed for assessing stress hyperglycemia and could provide prognostic information for various diseases. However, calculating SHR using random blood glucose (RBG) drawn on admission or fasting blood glucose (FBG) could lead to different results. This study intends to evaluate the association between SHR and functional outcomes in patients with acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (r-tPA) intravenous thrombolysis. METHODS: Data from 230 patients with AIS following thrombolytic therapy with r-tPA in the Third Affiliated Hospital of Wenzhou Medical University from April 2016 to April 2019 were retrospectively reviewed. SHR1 was defined as [RBG (mmol/L)]/[HbA1c (%)] and SHR2 was defined as [FBG (mmol/L)]/[HbA1c (%)]. The outcomes included early neurological improvement (ENI), poor function defined as a modified Rankin Scale score (mRS) of 3-6, and all-cause death in 3 months. Multivariable logistic regression was performed to estimate the association between SHR and adverse outcomes. RESULTS: After adjustment for possible confounders, though patients with AIS with higher SHR1 tend to have a higher risk of poor outcome and death and unlikely to develop ENI, these did not reach the statistical significance. In contrast, SHR2 was independently associated with poor functional outcome (per 0.1-point increases: odds ratios (OR) = 1.383 95% CI [1.147-1.668]). Further adjusted for body mass index (BMI), triglyceride-glucose index (TyG), and diabetes slightly strengthen the association between SHR (both 1 and 2) and adverse outcomes. In subgroup analysis, elevated SHR1 is associated with poor functional outcomes (per 0.1-point increases: OR = 1.246 95% CI [1.041-1.492]) in non-diabetic individuals and the association between SHR2 and the poor outcomes was attenuated in non-cardioembolic AIS. CONCLUSION: SHR is expected to replace random or fasting glucose concentration as a novel generation of prognostic indicator and a potential therapeutic target.

Background and Purpose: Systemic immune-inflammation index (SII), a novel inflammation index derived from counts of circulating platelets, neutrophils and lymphocytes, has been studied in developing incident cancer. However, the clinical value of SII in acute ischemic stroke (AIS) patients had not been further investigated. Therefore, we aimed to explore the association between SII and severity of stroke as well as 3-month outcome of AIS patients. Methods: A total of 216 AIS patients receiving intravenous thrombolysis (IVT) and 875 healthy controls (HCs) were retrospectively recruited. Blood samples were collected within 24h after admission. Severity of stroke was assessed by the National Institute of Health stroke scale (NIHSS) scores on admission and poor 3-month functional outcome was defined as Modified Rankin Scale (mRS) > 2. Results: SII levels in AIS patients were higher than in HCs. The cut-off value of SII is 545.14× 10 9 /L. Patients with SII > 545.14× 10 9 /L had higher NIHSS scores (median: 5 vs 9, p < 0.001), a positive correlation between SII and NIHSS was observed ( rs = 0.305, p < 0.001). Multivariate logistic regression analyses showed that high SII was one of the independent risk factors for poor prognosis at 3 months of AIS patients (OR = 3.953, 95% CI = 1.702– 9.179, p = 0.001). The addition of SII to the conventional prognostic model improved the reclassification (but not discrimination) of the functional outcome (net reclassification index 39.3%, p = 0.007). Conclusion: SII is correlated with stroke severity at admission and can be a novel prognostic biomarker for AIS patients treated with IVT. Keywords: systemic immune-inflammation index, ischemic stroke, inflammation, prognosis

SCOPE: Methionine restriction (MR) is known to potently alleviate inflammation and improve gut microbiome in obese mice. The gut microbiome exhibits diurnal rhythmicity in composition and function, and this, in turn, drives oscillations in host metabolism. High-fat diet (HFD) strongly altered microbiome diurnal rhythmicity, however, the role of microbiome diurnal rhythmicity in mediating the improvement effects of MR on obesity-related metabolic disorders remains unclear. METHODS AND RESULTS: 10-week-old male C57BL/6J mice are fed a low-fat diet or HFD for 4 weeks, followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 weeks. Analyzing microbiome diurnal rhythmicity at six time points, the results show that HFD disrupts the cyclical fluctuations of the gut microbiome in mice. MR partially restores these cyclical fluctuations, which lead to time-specifically enhance the abundance of short-chain fatty acids producing bacteria, increases the acetate and butyric, and dampens the oscillation of inflammation-related Desulfovibrionales and Staphylococcaceae over the course of 1 day. Notably, MR, which protects against systemic inflammation, influences brain function and synaptic plasticity. CONCLUSION: MR could serve as a potential nutritional intervention for attenuating obesity-induced cognitive impairments by balancing the circadian rhythm in microbiome-gut-brain homeostasis.

Background: This study aimed to cluster newly diagnosed patients and patients with long-term diabetes and to explore the clinical characteristics, risk of diabetes complications, and medication treatment related to each cluster. Research Design and Methods: K-means clustering analysis was performed on 1,060 Chinese patients with type 2 diabetes based on five variables (HbA1c, age at diagnosis, BMI, HOMA2-IR, and HOMA2-B). The clinical features, risk of diabetic complications, and the utilization of elven types of medications agents related to each cluster were evaluated with the chi-square test and the Tukey-Kramer method. Results: Four replicable clusters were identified, severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). In terms of clinical characteristics, there were significant differences in blood pressure, renal function, and lipids among clusters. Furthermore, individuals in SIRD had the highest prevalence of stages 2 and 3 chronic kidney disease (CKD) (57%) and diabetic peripheral neuropathy (DPN) (67%), while individuals in SIDD had the highest risk of diabetic retinopathy (32%), albuminuria (31%) and lower extremity arterial disease (LEAD) (13%). Additionally, the difference in medication treatment of clusters were observed in metformin (p = 0.012), α-glucosidase inhibitor (AGI) (p = 0.006), dipeptidyl peptidase 4 inhibitor (DPP-4) (p = 0.017), glucagon-like peptide-1 (GLP-1) (p <0.001), insulin (p <0.001), and statins (p = 0.006). Conclusions: The newly diagnosed patients and patients with long-term diabetes can be consistently clustered into featured clusters. Each cluster had significantly different patient characteristics, risk of diabetic complications, and medication treatment.