Interventional metabology: A review of bariatric arterial embolization and endovascular denervation for treating metabolic disorders.

The rising prevalence of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM) poses a major challenge to global health. Existing therapeutic approaches have limitations, and there is a need for new, safe, and less invasive treatments. Interventional metabolic therapy is a new addition to the treatment arsenal for metabolic disorders. This review focuses on two interventional techniques: bariatric arterial embolization (BAE) and endovascular denervation (EDN). BAE involves embolizing specific arteries feeding ghrelin-producing cells to suppress appetite and promote weight loss. EDN targets nerves that regulate metabolic organs to improve glycemic control in T2DM patients. We describe the current state of these techniques, their mechanisms of action, and the available safety and effectiveness data. We also propose a new territory called "Interventional Metabology" to encompass these and other interventional approaches to treating metabolic disorders.

Exosomal miR-140-3p and miR-143-3p from TGF-ß1-treated pancreatic stellate cells target BCL2 mRNA to increase ß-cell apoptosis.

BACKGROUND: People with chronic pancreatitis (CP) normally develop a fibrotic pancreas with reduced ß-cell mass. Limited studies have focused on the development and pathogenesis of CP-related diabetes. MiRNAs packaged as exosomes are the key regulators of ß-cell dysfunction. This study aimed to define the effect of exosomal miRNA from activated pancreatic stellate cells (PSCs) on ß-cells. METHODS: Exosomes in the supernatants of mouse PSCs lines were extracted via ultracentrifugation and then identified. The role of exosomes secreted by transforming growth factor-ß1 (TGF-ß1)-treated PSCs in ß-cell function was assessed. MiRNAs were prepared from exosomes extracted from TGF-ß1-treated and untreated PSCs (T-Exo or C-Exo), and the miRNA expression profiles were compared by microarray. Then, miR-140-3p and miR-143-3p were overexpressed or inhibited in MIN6 cells and islets to determine their molecular and functional effects. RESULTS: Exosomes were the predominant extracellular vesicles secreted by PSCs into the culture medium. The MIN6 cells incubated with T-Exo had less insulin secretion and lower viability than the MIN6 cells incubated with PBS or C-Exo. MiR-140-3p and miR-143-3p were notably upregulated in T-Exo. Enhancing the expression of miR-140-3p and miR-143-3p in ß-cells decreased the cell count and viability and increased the cleaved caspase-3 levels. Mechanistically, T-Exo mediated the intercellular transfer of miR-140-3p and miR-143-3p by targeting the B-cell lymphoma 2 gene in recipient ß-cells to induce cell death. CONCLUSIONS: Exosomal miRNA transfer as a communication mode between PSCs and ß-cells, which may be explored for its therapeutic utility.

Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis.

Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarkers of DEP and their potential molecular mechanisms. Based on GSE76896 dataset, which was acquired from Gene Expression Omnibus (GEO), we identified 373 genes by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. In addition, protein-protein interaction (PPI) network analysis and cytoHubba were used to screen potential hub genes. Five hub genes were determined, comprising Toll-like receptor 4 (TLR4), ITGAM, ITGB2, PTPRC, and CSF1R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested macrophage activation and Toll-like receptor signaling pathway as important pathophysiological features of DEP. CIBERSORT suggested that TLR4 may regulate the immune pathway via macrophages. Next, we validated the expression and receiver operating characteristic curve (ROC) of the hub genes using the GSE164416 dataset. In addition, we used miRNet to predict the target miRNAs of hub genes and intersected them with common miRNAs in diabetes from the Human MicroRNA Disease Database (HMDD), which was used to propose a possible mechanistic model for DEP. The miRNA-mRNA network showed that has-miR-155-5p/has-miR-27a-3p/has-miR-21-5p-TLR4 might lead to TLR4 signaling pathway activation in DEP. In conclusion, we identified five hub genes, namely, TLR4, ITGAM, ITGB2, PTPRC, and CSF1R, as biomarkers to aid in the diagnosis of DEP and conducted an in-depth study of the pathogenesis of DEP at the genetic level.

Upward shift and elevational range contractions of subtropical mountain plants in response to climate change.

Elevational range shifts of mountain species in response to climate change have profound impact on mountain biodiversity. However, current evidence indicates great controversies in the direction and magnitude of elevational range shifts across species and regions. Here, using historical and recent occurrence records of 83 plant species in a subtropical mountain, Mt. Gongga (Sichuan, China), we evaluated changes in species elevation centroids and limits (upper and lower) along elevational gradients, and explored the determinants of elevational changes. We found that 63.9% of the species shifted their elevation centroids upward, while 22.9% shifted downward. The changes in centroid elevations and range size were more strongly correlated with changes in lower than upper limits of species elevational ranges. The magnitude of centroid elevation shifts was larger than predicted by climate warming and precipitation changes. Our results show complex changes in species elevational distributions and range sizes in Mt. Gongga, and that climate change, species traits and climate adaptation of species all influenced their elevational movement. As Mt. Gongga is one of the global biodiversity hotspots, and contains many threatened plant species, these findings provide support to future conservation planning.

Heat shock protein 90 inhibitor ameliorates pancreatic fibrosis by degradation of transforming growth factor-ß receptor.

BACKGROUND AND AIM: Pancreatic fibrosis increases pancreatic cancer risk in chronic pancreatitis (CP). Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis by transforming growth factor-ß (TGFß) has been shown to inhibit transforming growth factor-ß receptor (TGFßR)-mediated Smad and no-Smad signaling pathways. Thus, the effects of Hsp90 inhibitor on pancreatic fibrosis are evaluated in CP mice, and the association between Hsp90 and biological functions of PSCs is further investigated in vitro. METHODS: The effects of Hsp90 inhibitor 17AAG on pancreatic fibrosis were assessed in caerulein-induced CP mice, and primary PSCs were used to determine the role of Hsp90 inhibitor 17AAG in vitro. RESULTS: We observed increased expression of Hsp90 in pancreatic tissues of caerulein-induced CP mice. Hsp90 inhibitor 17AAG ameliorated pancreatic inflammation and fibrosis in caerulein-induced CP mice. In vitro, Hsp90 inhibitor 17AAG inhibited TGFß1-induced activation and extracellular matrix accumulation of PSCs by blocking TGFßR-mediated Smad2/3 and PI3K /Akt/GSK-3ß signaling pathways.Hsp90 inhibitor 17AAG degraded TGFßRII by a ubiquitin-proteasome pathway, co-immunoprecipitation showed an interaction between Hsp90 and TGFßRII in PSCs. CONCLUSIONS: The study suggests that an Hsp90 inhibitor 17AAG remarkable prevents the development of pancreatic fibrosis in caerulein-induced CP mice, and suppresses activation and extracellular matrix accumulation of PSCs in vitro. The current results provide a potential treatment strategy based on Hsp90 inhibition for pancreatic fibrosis in CP.

Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What's Known and What's to Know.

The clinical significance of diabetes arising in the setting of pancreatic disease (also known as diabetes of the exocrine pancreas, DEP) has drawn more attention in recent years. However, significant improvements still need to be made in the recognition, diagnosis and treatment of the disorder, and in the knowledge of the pathological mechanisms. The clinical course of DEP is different from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). DEP develops in patients with previous existing exocrine pancreatic disorders which damage both exocrine and endocrine parts of pancreas, and lead to pancreas exocrine insufficiency (PEI) and malnutrition. Therefore, damage in various exocrine and endocrine cell types participating in glucose metabolism regulation likely contribute to the development of DEP. Due to the limited amount of clinical and experimental studies, the pathological mechanism of DEP is poorly defined. In fact, it still not entirely clear whether DEP represents a distinct pathologic entity or is a form of T2DM arising when ß cell failure is accelerated by pancreatic disease. In this review, we include findings from related studies in T1DM and T2DM to highlight potential pathological mechanisms involved in initiation and progression of DEP, and to provide directions for future research studies.

Serum REG Iα as a potential novel biomarker in cancer: An observational study.

The regulation of the gene-regenerating family member 1 alpha (REG Iα) played important roles in cancer cell biology. However, the correlation between its gene product serum REG Iα and cancer has not been evaluated. In this observational study, 130 hospitalized patients from the department of internal medicine in Zhongda Hospital Southeast University were included and assigned to cancer or noncancer groups. History, clinical, and laboratory data were obtained. Serum REG Iα levels and alanine aminotransferase were found significantly higher in patients with cancer (P < .001 and P < .05 respectively). Logistic regression analysis indicated that REG Iα was an independent risk factor for cancer (P < .001). The area under the curve of REG Iα was 0.764 and the optimal cut-off point of REG Iα was 46.97 ng/mL. Besides, the cancer patients with metastasis had significantly higher serum REG Iα levels than those in nonmetastasis cancer group (P < .05). In conclusion, serum REG Iα was significantly elevated in patients with cancer, and it might be a potential biomarker in predicting cancer occurrence and development.

Association of Serum PSP/REG Iα with Renal Function in Type 2 Diabetes Mellitus.

PURPOSE: Pancreatic stone protein/regenerating protein I (PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG I. METHODS: This cross-sectional study was conducted at Zhongda Hospital, affiliated with Southeast University in China. Serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG I. RESULTS: Serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG IP < 0.05). The level of PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG I. CONCLUSIONS: Serum PSP/REG Iα level is significantly upregulated in T2DM patients and reflects renal function in both T2DM and nondiabetic control groups. The relationship between PSP/REG Iα and eGFR suggested that PSP/REG Iα might be a potential indicator of renal dysfunction.α) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG I.

The alterations of gut microbiota in mice with chronic pancreatitis.

BACKGROUND: The changes of intestinal microbiome are associated with inflammatory, metabolic, and malignant disorders, and there are no studies assessing the intestinal microbiota of mice with chronic pancreatitis (CP). Thus, we aim to investigate the variations in diversity, composition and function of intestinal microbiota in CP mice. METHODS: Sixteen male C57BL/6 mice were randomly selected, and divided into two groups, treated intraperitoneally with saline (normal control group, CT group) or ethanol + cerulein (experimental group, CP group) for 6 weeks. Body weight as measured in entire processes. Histopathological examination of CP index was conducted to verify the CP induction. Extracted DNA from colon samples was used for Illumina HiSeq sequencing of the bacterial V4 region of 16S rRNA gene and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Functional profiling of microbial communities was predicted with BugBase. RESULTS: Significant alterations of the gut microbiota were found in the CP mice compared to CT groups, as revealed by significant decrease in bacterial richness and diversity, declined the relative abundance of Lachnospiraceae_NK4A136, Ruminiclostridium and Roseburia, and increased the relative abundances of Bacteroides and Alloprevotella genera. Analysis of microbial community-level phenotypes revealed significant differences in nine phenotypes (aerobic, anaerobic, containing mobile elements, facultatively anaerobic, biofilm forming, gram-negative, gram-positive, potentially pathogenic, and stress tolerant) between CP group and CT group. CONCLUSIONS: This study indicated that mice with CP had a distinct microbiota profile.

[Design and application of a new patient transfer device].

OBJECTIVE: In daily medical work, most of the critically ill patients who cannot move by themselves are pulled and lifted by manpower, often relying on the cooperation of many doctors and nurses, which not only increases the risk of transfer and patients' discomfort, but also causes certain skeletal and muscle damage to the porters. The emergency department of the First Hospital of Jiaxing City, Zhejiang Province designed a kind of patient transfer device, and obtained the National Utility Model Patent (ZL 2018 2 0579844.X). The transfer device is composed of upper frame, lower frame and base. The upper frame and the lower frame are rectangular and in a horizontal position. The upper frame can slide laterally through the circular tubes which are fixed on the lower frame. The lower part of the base is provided with four universal foot brake wheels. During the usage, the booster frame facilitates the transfer of patients by the rolling and two sliding tracks of the circular tube, which can make patients move smoothly and comfortably, and reduce the working intensity of the transporter. This device has good practical value.

Altitudinal biodiversity patterns of seed plants along Gongga Mountain in the southeastern Qinghai-Tibetan Plateau.

The mechanisms underlying elevation patterns in species and phylogenetic diversity remain a central issue in ecology and are vital for effective biodiversity conservation in the mountains. Gongga Mountain, located in the southeastern Qinghai-Tibetan Plateau, represents one of the longest elevational gradients (ca. 6,500 m, from ca. 1,000 to 7,556 m) in the world for studying species diversity patterns. However, the elevational gradient and conservation of plant species diversity and phylogenetic diversity in this mountain remain poorly studied. Here, we compiled the elevational distributions of 2,667 native seed plant species occurring in Gongga Mountain, and estimated the species diversity, phylogenetic diversity, species density, and phylogenetic relatedness across ten elevation belts and five vegetation zones. The results indicated that species diversity and phylogenetic diversity of all seed plants showed a hump-shaped pattern, peaking at 1,800-2,200 m. Species diversity was significantly correlated with phylogenetic diversity and species density. The floras in temperate coniferous broad-leaved mixed forests, subalpine coniferous forests, and alpine shrublands and meadows were significantly phylogenetically clustered, whereas the floras in evergreen broad-leaved forests had phylogenetically random structure. Both climate and human pressure had strong correlation with species diversity, phylogenetic diversity, and phylogenetic structure of seed plants. Our results suggest that the evergreen broad-leaved forests and coniferous broad-leaved mixed forests at low to mid elevations deserve more conservation efforts. This study improves our understanding on the elevational gradients of species and phylogenetic diversity and their determinants and provides support for improvement of seed plant conservation in Gongga Mountain.

New-Onset Diabetes Mellitus After Chronic Pancreatitis Diagnosis: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of this study was to assess the occurrence of new-onset diabetes mellitus (DM) after chronic pancreatitis (CP) diagnosis via systematic review and meta-analysis. METHODS: A systematic review of literature and meta-analysis of relevant reports were performed. The primary outcome measures studied were newly diagnosed DM and DM treated with insulin. For the binary outcomes, pooled prevalence and 95% confidence interval (CI) were calculated. METHODS: Fifteen studies involving 8970 patients were eligible. The incidence of new-onset DM after CP diagnosis was 30% (95% CI, 27%-33%). Among all patients, 17% (95% CI, 13%-22%) developed insulin-dependent new-onset DM. The prevalence of newly diagnosed DM after CP diagnosis increased from 15% within 36 months to 33% after 60 months. The proportion of alcoholic CP, sex, age, and body mass index had minimal effect on the studied outcomes. CONCLUSIONS: This systematic review identified a clinically relevant risk of new-onset DM after CP diagnosis. Therefore, patients should be informed of the risk of DM and monitored.

Incidence of New Onset Diabetes Mellitus Secondary to Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Background and Aims: Patients who have an episode of acute pancreatitis (AP) frequently develop diabetes mellitus (DM) over time. The reported incidence of DM after AP varies depending on the severity, etiology and the extent of pancreatic necrosis during AP. We performed a systematic review to determine the incidence of new-onset DM after AP episode (s), and compared the rate of DM in AP patients based upon different disease characteristics. Methods: A total of 31 relevant studies with 13894 subjects were collected from Medline, Embase, and Web of Science. Stata 15 software was used for data analyses in the meta-analysis. Results: The random-effects pooled incidence was 23.0% for DM (95% CI 16.0-31.0%) and 15.0% (95% CI 9.0-23.0%) for DM treated with insulin. We noted substantial heterogeneity in incidence estimates for DM and DM treated with insulin (I 2 = 95.61 and 71.78%; both p < 0·001). The DM incidence was higher in the populations that had a severe AP (SAP) episode than in those with mild acute pancreatitis (MAP) (39 vs. 14%). Patients that displayed pancreatic necrosis during the AP attack(s) had a higher frequency of DM than those without necrosis (37 vs. 11%). In addition, the pooled incidence of DM was higher after alcoholic compared to biliary AP (28 vs. 12%). The incidence of insulin use after SAP and alcoholic AP was 21 and 18%, respectively, with very low heterogeneities. According to duration of follow-up, the pooled rate of DM and insulin use within 5 years after AP was 20 and 14%, while the rate associated with follow-up duration of more than 5 years was elevated to 37 and 25%, respectively. On meta-regression, year of publication, male proportion, age at DM test, and duration of follow-up were neither positively nor negatively associated with the incidence of DM and DM treated with insulin in patients who had a prior AP attack. Conclusion: Patients with AP developed DM after discharge from hospital with a frequency of about 23%. SAP, alcoholic AP and acute necrotizing pancreatitis (ANP) were associated with increased incidence of DM. Assessments of severity, etiology, and pancreatic necrosis are critical for predicting DM development after AP.

Association of Serum PSP/REG Iα with Renal Function in Pregnant Women.

Pancreatic stone protein/regenerating protein Iα (PSP/REG Iα) is a secretory protein produced in the pancreas, but its expression has also been observed in the kidney. It may be associated with kidney dysfunction. This study investigates the possible association between PSP/REG Iα and kidney function in pregnant women. Serum PSP/REG Iα levels were measured by a specific ELISA enzyme-linked immunosorbent assay. Maternal information and clinical and biochemical parameters were collected. Estimated glomerular filtration rate (eGFR) was calculated for all individuals to evaluate their renal function. Spearman's correlation and multiple linear regression analyses were performed to assess the associations between PSP/REG Iα and eGFR, serum creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA). A total of 595 pregnant women were enrolled in the study. Participants with mildly reduced eGFR had higher PSP/REG Iα levels [50.49 (35.02, 58.64)] than in the general population [26.84 (21.02, 33.07)] (p < 0.001). Included participants were stratified into PSP/REG Iα quartiles; significant differences were observed in the levels of eGFR, serum Cr, BUN, and UA. PSP/REG Iα was negatively correlated with eGFR (r = -0.402, p < 0.001) and positively associated with serum Cr (r = 0.468, p < 0.001), BUN (r = 0.166, p < 0.001), and UA (r = 0.207, p < 0.001). The linear regression analysis indicated that PSP/REG Iα was associated with UA, BUN, and eGFR. High PSP/REG Iα concentrations were closely associated with renal dysfunction in pregnant women. Our study provides clinical evidence that serum PSP/REG Iα levels could be a novel biomarker for assessment of renal function in pregnant women.

Probiotics improve glucose and lipid metabolism in pregnant women: a meta-analysis.

BACKGROUND: This study aims to assess the effects of probiotic supplementation on the maternal metabolism and the risk of development of gestational diabetes mellitus (GDM) in the pregnant women by a meta-analysis of relevant randomized controlled trials (RCTs). METHODS: The medical literature was searched from PubMed, Web of Science and the Cochrane Library since inception to October 2017. Two investigators independently performed the data extraction and quality assessment. The mean differences (MD) or standardized mean differences (SMD) or relative risk (RR) with 95% confidence intervals (CIs) were calculated with the random-effects model. RESULTS: From 648 citations, a total of ten RCTs published in 13 articles with 1,139 participants met the inclusion criteria. The meta-analysis showed that probiotics supplementation effectively reduced the fasting blood glucose (FBG) levels (MD -0.11 mmol/L, P=0.0003), serum insulin levels (MD -2.06 µU/mL, P<0.00001), insulin resistance (HOMA-IR) (MD -0.38, P<0.00001). The study found a significant effect of probiotics on decreasing the risk of GDM [risk ratio (RR) 0.52, P=0.003) in early pregnancy. Additionally, there were statistically significant reductions in the total cholesterol and triglycerides levels after probiotic interventions (SMD -0.56, P=0.03; SMD -0.66, P=0.04), respectively. CONCLUSIONS: Our study shows that the probiotic use was associated with improved glucose and lipid metabolism in the pregnant women, and might also contribute to the reduced risk of GDM.

Chitosan-microcapsulated insulin alleviates mesenteric microcirculation dysfunction via modulating COX-2 and VCAM-1 expression in rats with diabetes mellitus.

BACKGROUND: The study of the experiment was to display the therapeutic function of insulin-loaded chitosan (insulin/chitosan) on mesenteric microcirculation via down-regulating cyclooxygenase-2 (COX-2) and vascular cell adhesion molecule (VCAM-1) expressions in rats with diabetes mellitus (DM) as compared to free insulin. METHODS: Diabetic rats were administrated with 24 U/kg insulin or 120 U/kg insulin/chitosan compounds. The blood and mesenteriums were collected, blood glucose levels, arteriole velocity, arteriole diameter, venular diameter, and hemodiapedesis were measured, and COX-2, VCAM-1 expressions were measured in mesenteriums tissues. RESULTS: Both insulin and insulin/chitosan administration decreased blood glucose and improved the state of mesenteric microcirculation through down-regulating COX-2 and VCAM-1 expressions as compared to DM groups, while insulin/chitosan remarkably augmented this functions. CONCLUSION: Chitosan-microcapsulated insulin alleviates mesenteric microcirculation dysfunction via modulating COX-2 and VCAM-1 expressions in rats with DM.

Low vitamin D levels are associated with cognitive impairment in patients with Hashimoto thyroiditis.

BACKGROUND: Cognitive impairment is commonly observed in patients with Hashimoto thyroiditis (HT). Low levels of vitamin D have been correlated with cognitive impairment in non-HT population. We examined the association of vitamin D levels with cognitive impairment in patients with HT. METHODS: We recruited 194 patients with HT and 200 healthy volunteers. Levels of serum 25-hydroxyvitamin D (25(OH)D) were measured using a competitive protein-binding assay. Cognitive funtion was assessed using Montreal Cognitive Assessment score (MoCA). Subjects with a MoCA scores < 26 are considered as having mild cognitive impairment (MCI). Multivariate analysis was performed using logistic regression models. RESULTS: Fifty-five HT patients (28.4%) were diagnosed as having MCI. Patients with MCI had significantly lower 25(OH)D levels when compared with patients without MCI (33.9 ± 6.2 vs. 44.3 ± 9.6 nmol/L, P < 0.001). Significant differences in 25(OH)D quartiles of HT patients were observed between the patients with MCI and the patients without MCI (P < 0.001). In multivariate analyses, serum 25(OH)D levels (≤ 34.0 and ≥ 47.1 nmol/L) were significantly associated with cognitive impairment in patients with HT (OR 6.279, 95% CI 2.673-14.834, P < 0.001; OR 0.061, 95% CI 0.008-0.491, P = 0.009, respectively). CONCLUSION: Our results demonstrate an important association between serum vitamin D levels and cognitive impairment in patients with HT.

[Effects of insulin caliper for blood glucose control on glucose control in emergent and critical patients].

OBJECTIVE: To observe the effects of insulin caliper for blood glucose control on glycemic central tendency, fluctuation and incidence of hypoglycemia, etc., in emergent and critical patients to evaluate its application value. METHODS: A prospective single-blinded randomized parallel controlled intervention study was conducted. One hundred patients with severe hyperglycemia requiring treatment with insulin infusion admitted to emergency department and intensive care unit (ICU) of the First Hospital of Jiaxing from November 2015 to November 2017 were enrolled, and they were divided into the caliper group (used patented product insulin calipers for blood glucose control to adjust insulin dose for blood glucose control) and the conventional group (used paper-based insulin dose modification scheme to adjust insulin dose for blood glucose control) on average by random number table, 50 in each group. The gender, age, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), the principal diseases, main factors affecting blood glucose (hepatic and renal insufficiency, hypoglycemic drugs, glucocorticoids, mechanical ventilation, enteral nutrition, parenteral nutrition, intravenous glucose use, etc.), blood glucose levels at each time node (once every 2 hours after insulin use and once every 4 hours after 16-72 hours), glycemic coefficient of variance (CV), glycemic lability index (GLUGLI) and mean amplitude of glycemic excursion (GLUMAGE), insulin dose, incidence of hypoglycemia, proportion of achieving the glucose control target at each time point, the length of ICU stay and hospitalization cost per patient were recorded and compared between the two groups. RESULTS: After excluding those with incomplete data and withdraw in the midway, 92 patients were enrolled in the analysis finally, 47 in caliper group and 45 in conventional group. There were no significant differences in the incidence of the gender, age, APACHE II, SOFA, presence of infection at admission, previous diabetes history, glycosylated hemoglobin level, blood glucose at admission, proportion of patients after surgery, major diseases at admission and major factors affecting blood glucose between the two groups. A total of 1 379 blood glucose measurements were obtained in the caliper group and 1 332 blood glucose measurements were obtained in the conventional group. The glycemic measurements in caliper group were significantly lower than that in conventional group at each time point from 6-72 hours. Compared with conventional group, GLUGLI and GLUMAGE were significantly decreased in the caliper group [GLUGLI: 12.96 (8.73, 19.58) vs. 23.27 (13.07, 44.61), GLUMAGE (mmol/L): 0.66±0.22 vs. 0.87±0.28, both P < 0.01]; there was a tendency towards decreasing incidence of hypoglycemia in the caliper group [8.51% (4/47) vs. 15.56% (7/45)], but no statistical difference was found (P > 0.05); the proportion of achieving the glucose control target was significantly increased in the caliper group [41.99% (579/1 379) vs. 27.18% (362/1 332), P < 0.01]. There were no significant differences in glycemic CV, insulin dose, proportion of hypoglycemic measurements in total measurements, and the length of ICU stay, the length of hospital stay, incidence of nosocomial infection, patient prognosis and cost between the two groups. CONCLUSIONS: For emergent and critical patients, insulin caliper for blood glucose control presents favorable application value for achieving glucose control target, reducing glycemic fluctuation, and lowering the incidence of hypoglycemia. CLINICAL TRIAL REGISTRATION: China clinical trial registration center, ChiCTR1800015024.

OCT1-Mediated Metformin Uptake Regulates Pancreatic Stellate Cell Activity.

BACKGROUND/AIMS: Metformin treatment is reported to be associated with a lower incidence of and mortality from pancreatic cancer (PC) in type 2 diabetes patients. Activated pancreatic stellate cells (PSCs) are key stroma cells responsible for pancreatic fibrogenesis and PC progression. However, little research is about the influence of metformin on PSCs. Given the potential beneficial effects of metformin on PC, pancreatic tumour stroma is an important target for new therapeutics. We observed the effects of metformin on PSCs. We investigated the effects of metformin on human PSCs proliferation and the production of extracellular matrix (ECM) proteins. METHODS: Cells were cultured with different concentrations of metformin (0-10 mmol/L). Cell proliferation was determined by immunofluorescence staining for nuclear Ki67 labelling. ECM production was studied by quantitative real-time polymerase chain reaction, immunoblotting and immunofluorescence microscopy. Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. RESULTS: Our results showed that metformin inhibited PSCs proliferation and decreased the production of ECM proteins by activation of AMPK phosphorylation. Silencing of OCT1 expression resulted in a reduction in the effects of metformin on PSCs activity. CONCLUSIONS: Collectively, the data indicate that OCT1 may contribute to uptake metformin and regulate PSCs activity. OCT1 is a target of metformin in regulating PSCs activity.

Esculetin Attenuates the Growth of Lung Cancer by Downregulating Wnt Targeted Genes and Suppressing NF-KB / La esculetina atenúa el crecimiento del cáncer de pulmón por regulación negativa de los genes diana de Wnt y supresión de NF-KB

Introduction: Esculetin was identified to inhibit cell proliferation and induce apoptosis or cell cycle arrest in several cancer cell lines. However, the effect of esculetin on lung cancer remains elusive. Methods: The anti-proliferative role of esculetin in murine Lewis lung carcinoma (LLC) cells was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. BALB/c mice were subcutaneously injected with LLC cells to investigate the inhibitory effect of esculetin on the growth of lung cancer xenograft. Invasive ability was detected in esculetin treated and untreated LLC cells by transwell assay. The association between esculetin and Wnt/Beta-catenin signaling, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), was confirmed by testing the expression of c-myc, Cyclin D1 and NF-κB using Western blot. Results: Esculetin treatment in LLC cells led to significant decrease of cell proliferation in a time- and dose-dependent manner. After injection of LLC cells into mice, reduced size and weight of tumors were observed in esculetin treated mice compared to untreated mice. However, no difference in cell invasion was observed between the treated and untreated LLC cells. Notably decreased expression of c-myc, Cyclin D1 and NF-κB were observed in LLC cells with esculetin treatment compared to untreated cells. Conclusion: Esculetin plays an inhibitory role in the growth of lung cancer by down-regulating c-myc, Cyclin D1 and NF-κB (AU)

Introducción: Se ha determinado que la esculetina inhibe la proliferación celular e induce la apoptosis o la detención del ciclo celular en varias líneas celulares de cáncer. Sin embargo, su efecto sobre el cáncer de pulmón es todavía desconocido. Métodos: Se estudió el papel antiproliferativo de la esculetina en células murinas de carcinoma pulmonar de Lewis (LLC) mediante ensayos de bromuro de 3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazolio (MTT) y de formación de colonias. Se inyectaron subcutáneamente células LLC a ratones BALB/c para investigar el efecto inhibidor de la esculetina sobre el crecimiento del xenoinjerto de cáncer de pulmón. La capacidad invasiva en células LLC tratadas o no tratadas con esculetina se evaluó mediante el ensayo transwell. La asociación entre la señalización de la esculetina y la de Wnt/β-catenina, y con el factor nuclear potenciador de las cadenas ligeras kappa de células B activadas (NF-κB) se confirmó midiendo la expresión de c-myc, de ciclina D1 y NF- κB usando Western blot. Resultados: El tratamiento con esculetina de las células LLC disminuyó significativamente la proliferación celular de una manera dependiente del tiempo y de la dosis. Tras la inyección de células LLC en ratones, se observó que los tumores de los ratones tratados con esculetina eran de menor tamaño y peso que los de los ratones no tratados. Sin embargo, no se observó diferencia en la invasividad celular entre las células LLC tratadas y las no tratadas. Se destacó la disminución de la expresión de c-myc, ciclina D1 y NF-κB en células LLC tratadas con esculetina en comparación con células no tratadas. Conclusión: La esculetina desempeña un papel inhibitorio en el crecimiento del cáncer de pulmón a través de la regulación de c-myc, ciclina D1 y NF-κ B (AU)