Association Between HLA-DRB1 Alleles and Graves' Disease in Asian Populations: A Meta-Analysis.

Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism. Genetic studies have shown that human leukocyte antigen (HLA) plays an important role in the development of GD. In this article, we performed a meta-analysis determined to evaluate the relationship between HLA-DRB1 alleles and GD. This meta-analysis included 9 studies (3582 cases in the case group and 23070 cases in the control group) and 27 alleles was performed. The combined results showed that, compared with the control group, GD patients have a significant increase in the frequency of DRB1*1403 (OR=2.50, 95% CI=1.78-3.51, pc<0.0001) and have a significant decrease in frequencies of DRB1* 0101 (OR=0.45, 95% CI=0.34-0.59, pc<0.0001) and DRB1*0701 (OR=0.44, 95% CI=0.35-0.55, pc<0.0001). The meta-analysis indicated that, in Asian populations, DRB1*1403 is a risk allele for GD, and DRB1*0101 and DRB1*0701 are protective against the occurrence of GD. We surprisingly discovered that the susceptibility alleles for GD in Asian populations are completely different from Caucasians and the protective alleles for GD in Asians are quite similar to those of Caucasians. The results of our study may provide new opportunities for gene-targeted therapy for GD in Asian populations.

The effects of economic status on metabolic control in type 2 diabetes mellitus at 10 metabolic management centers in China.

OBJECTIVE: This study investigated the association of economic status with metabolic index control in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 37 454 T2DM patients from 10 National Metabolic Management Centers in China were recruited and categorized into two groups: a high-gross domestic product (GDP) group (n = 23 993) and a low-GDP group (n = 13 461). Sociodemographic characteristics, medical histories, and lifestyle factors were recorded. Logistic regression and interaction analysis were performed to evaluate the association of economic status and healthy lifestyle with metabolic control. RESULTS: Compared to the low-GDP group, there were fewer patients with glycated hemoglobin (HbA1c) levels ≥7% in the high-GDP group. Fewer patients with a high GDP had an abnormal metabolic state (HbA1c ≥ 7%, blood pressure [BP] ≥130/80 mm Hg, total cholesterol [TCH] ≥4.5 mmol/L or body mass index [BMI] ≥24 kg/m2 ). The risks of developing HbA1c ≥ 7% (odds ratios [OR] = 0.545 [95% CI: 0.515-0.577], p < .001), BP ≥ 130/80 mm Hg (OR = 0.808 [95% CI: 0.770-0.849], p < .001), BMI ≥ 24 kg/m2 (OR = 0.840 [95% CI: 0.799-0.884], p < .001), and an abnormal metabolic state (OR = 0.533 [95% CI: 0.444-0.636], p < .001) were significantly lower in the high-GDP group even after adjustment for confounding factors. Younger participants; those with a family history of diabetes, normal weight, and a physical activity level up to standard; and those who did not drink alcohol in the high-GDP group were predisposed to better glycemic levels. CONCLUSIONS: T2DM patients in economically developed regions had better metabolic control, especially glycemic control. A healthy lifestyle had an additive effect on achieving glycemic goals, even among high-GDP patients.

Association of visceral fat area or BMI with arterial stiffness in ideal cardiovascular health metrics among T2DM patients.

BACKGROUND: "Obesity paradox" occurs in type 2 diabetes mellitus (T2DM) patients when body mass index (BMI) is applied to define obesity. We examined the association of visceral fat area (VFA) as an obesity measurement with arterial stiffness in seven ideal cardiovascular health metrics (ICVHMs). METHODS: A total of 29 048 patients were included in the analysis from June 2017 to April 2021 in 10 sites of National Metabolic Management Centers. ICVHMs were modified from the recommendations of the American Heart Association. Brachial-ankle pulse wave velocity (BaPWV) ≥ 1400 cm/s was employed to evaluate increased arterial stiffness. Multivariate regression models were used to compare the different effects of BMI and VFA on arterial stiffness. RESULTS: Lower VFA was more strongly associated with low BaPWV than lower BMI when other ICVHMs were included (adjusted odds ratio [OR], 0.85 [95% confidence interval [CI], 0.80-0.90] vs OR 1.08 [95% CI, 1.00-1.17]). Multivariable-adjusted ORs for arterial stiffness were highest in patients with the VAT area VFA in the range of 150-200 cm2 (adjusted OR, 1.26 [95% CI 1.12-1.41]). Compared with participants with VAT VFA < 100 cm2 , among participants with higher VAT VFA, the OR for arterial stiffness decreased gradually from 1.89 (95% CI, 1.73-2.07) in patients who had ≤1 ICVHM to 0.39 (95% CI, 0.25-0.62) in patients who had ≥5 ICVHMs. CONCLUSION: In patients with T2DM, using VAT for anthropometric measures of obesity, VFA was more relevant to cardiovascular risk than BMI in the seven ICVHMs. For anthropometric measures of obesity in the ICVHMs to describe cardiovascular risk VFA would be more optimal than BMI.

Proteomic analysis by 4D label-free MS-PRM identified that Nptx1, Ptpmt1, Slc25a11, and Cpt1c are involved in diabetes-associated cognitive dysfunction.

BACKGROUND: Diabetes-associated cognitive dysfunction (DACD) is a chronic ailment that exerts a substantial influence on the overall well-being of individuals. The hippocampus assumes a pivotal role in the progression and sustenance of cognitive impairment. The identification of differentially expressed proteins (DEPs) in the hippocampus is crucial for understanding the mechanisms of DACD. METHODS: A rat model of DACD was established by a high-fat diet combined with streptozotocin intraperitoneal injection. The Morris water maze (MWM), hematoxylin and eosin (H&E) staining, Nissl staining, and transmission electron microscope (TEM) were performed on the rats. The proteins expressed in the hippocampus were detected using 4D label-free quantitative proteomics. Four DEPs, namely Nptx1, Ptpmt1, Slc25a11, and Cpt1c, were validated using parallel reaction monitoring (PRM). RESULT: Our study found that hippocampal lesions were present in the DACD rat models. There were 59 up-regulated and 98 down-regulated DEPs in the Model group compared to the Control group. We found that the levels of Nptx1, Ptpmt1, Slc25a11, and Cpt1c were elevated in the Model group, which are important for cell mitochondrial function. It should be noted that in our study, we only used PRM to validate the expression of these proteins. However, more evidence is needed to establish the relationship between these protein changes and DACD. CONCLUSION: Our research results may provide further insight into the molecular pathology of hippocampal injury in DACD. In addition, further studies and clinical trials are required to confirm our findings and establish a more conclusive molecular mechanism for DACD.

Prebiotic inulin nanocoating for pancreatic islet surface engineering.

Pancreatic islet surface engineering has been proposed as an "easy-to-adopt" approach to enhance post-transplantation islet engraftment for treatment against diabetes. Inulin is an FDA-approved dietary prebiotic with reported anti-diabetic, anti-inflammatory, anti-hypoxic and pro-angiogenic properties. We therefore assessed whether inulin would be a viable option for islet surface engineering. Inulin was oxidized to generate inulin-CHO, which would bind to the cell membrane via covalent bond formation between -CHO and -NH2 across the islet cell membrane. In vitro assessments demonstrated enhanced islet viability and better glucose-induced insulin secretion from inulin-coated (5 mg mL-1) islets, which was accompanied by enhanced revascularization, shown as significantly enhanced tube formation and branching of islet endothelial MS1 cells following co-culture with inulin-coated islets. Reduction of cytokine-induced cell death was also observed from inulin-coated islets following exposure to pro-inflammatory cytokine LPS. LPS-induced ROS production was significantly dampened by 44% in inulin-coated islets when compared to controls. RNA-seq analysis of inulin-coated and control islets identified expression alterations of genes involved in islet function, vascular formation and immune regulation, supporting the positive impact of inulin on islet preservation. In vivo examination using streptozotocin (STZ)-induced hyperglycemic mice further showed moderately better maintained plasma glucose levels in mice received transplantation of inulin-coated islets, attributable to ameliorated CD45+ immune cell infiltration and improved in vivo graft vascularization. We therefore propose islet surface engineering with inulin as safe and beneficial, and further assessment is required to verify its applicability in clinical islet transplantation.

Follow-up frequency and clinical outcomes in patients with type 2 diabetes: A prospective analysis based on multicenter real-world data.

BACKGROUND: To determine whether the follow-up frequency for type 2 diabetes mellitus (T2DM) patients in the National Metabolic Management Centers (MMCs) leads to different clinical outcomes. METHODS: A total of 19 908 T2DM patients with at least 6 months of facility-based follow-up were recruited in MMCs between June 2017 and April 2021 and divided into lower-frequency and higher-frequency follow-up (LFF and HFF) groups according to the median follow-up frequency of 2.0 (interquartile range 1.2) times per year. Metabolic parameters at baseline and at the last follow-up visit were analyzed. Multivariable linear regression models were performed to assess the relationship between follow-up frequency and between-group percentage changes, adjusting for the major covariables. Additional stratified analyses were conducted to evaluate the metabolic outcomes in the subgroups. RESULTS: The characteristics of the participants in the LFF and HFF groups were significantly different at baseline. Participants had significant improvements in multiple metabolic parameters after follow-up. Patients with HFF showed significantly greater decrease in percentage changes of fasting blood glucose (-4.95% ± 37.96% vs -2.21% ± 43.08%, P < .0001) and glycosylated hemoglobin (HbA1c) (-12.14% ± 19.78% vs -9.67% ± 20.29%, P < .0001) after adjustments compared to those with LFF. Furthermore, stratification analyses showed that significant between-group percentage changes of HbA1c were observed in those with younger age (<55 years) and higher HbA1c (>9%) at baseline (P for interaction <.001). CONCLUSIONS: HFF is associated with better metabolic outcomes. Participants, especially with younger age or worse HbA1c at baseline in the HFF group achieved better glycemic control than those in the LFF group.

Kidney disease parameters, metabolic goal achievement, and arterial stiffness risk in Chinese adult people with type 2 diabetes.

BACKGROUND: To investigate the arterial stiffness (AS) risk within urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) categories and the joint effect between kidney disease parameters and metabolic goal achievement on AS risk in adult people with type 2 diabetes (T2D). METHODS: A total of 27 439 Chinese participants with T2D from 10 National Metabolic Management Centers (MMC) were categorized into four albuminuria/decreased eGFR groups. The criteria for decreased eGFR and AS were eGFR <90 ml/min/1.73 m2 and brachial-ankle pulse wave velocity value >the 75th percentile (1770.0 cm/s). Three metabolic goals were defined as glycated hemoglobin <7%, BP <130/80 mmHg, andlow-density lipoprotein cholesterol <2.6 mmol/L. RESULTS: After full adjustment, odds ratios (ORs) for AS were highest for albuminuria and decreased eGFR (2.23 [1.98-2.52]) and were higher for albuminuria and normal eGFR (1.52 [1.39-1.67]) than for those with nonalbuminuria and decreased eGFR (1.17 [1.04-1.32]). Both UACR and eGFR in the subgroup or overall population independently correlated with AS risk. The achievement of ≥2 metabolic goals counteracted the association between albuminuria and AS risk (OR: 0.93; 95% CI: 0.80-1.07; p = .311). When the metabolic goals added up to ≥2 for patients with decreased eGFR, they showed significantly lower AS risk (OR: 0.65; 95% CI: 0.56-0.74; p < .001). CONCLUSIONS: Both higher UACR and lower eGFR are determinants of AS risk, with UACR more strongly related to AS than eGFR in adults with T2D. The correlation between albuminuria/decreased eGFR and AS was modified by the achievement of multiple metabolic elements.

Association of sedentary time and carotid atherosclerotic plaques in patients with type 2 diabetes.

BACKGROUND: Atherosclerosis is a common complication in patients with type 2 diabetes (T2DM). Multiple factors are involved in the development and progress of atherosclerosis. We evaluated the association of weekly sedentary time (WST) with carotid plaque formation. METHODS: After data cleaning, a total of 26 664 participants with T2DM from 10 National Metabolic Management Centers (MMCs) from June 2017 to April 2021 were enrolled. Self-reported lifestyle data including WST, sleeping time, smoking and drinking information, carotid artery ultrasound, and biochemical parameters were obtained. The independent association of carotid plaue with sedentary and other lifestyle behaviors was evaluated using multivariable logistic regression models, and odds ratio (OR) with 95% confidence interval (CI) were reported. Moreover, stratified analysis was conducted to demonstrate the influence of confounding factors. RESULTS: The mean (SD) age of the participants was 54.0 (11.6) years, and the median (interquartile range) WST was 35.0 (21.0, 42.0) h. Comparing with participants in the first tertile of WST, those in the second or third tertile of WST were younger and with a shorter duration of diabetes. There were positive associations between longer sedentary time and odds of artery plaque after adjustment, with corresponding ORs in the second and third tertile were 1.40 (95% CI: 1.31-1.50) and 1.67 (95% CI: 1.56-1.79), respectively. However, the effect of WST on plaque in patients aged 18-40 years old had no statistical significance; the p value in the third tertile was 0.163. CONCLUSIONS: In summary, higher WST appears to be associated with higher prevalence of carotid plaque in patients with T2DM, especially in aged populations.

Effects of basal and premixed insulin on glycemic control in type 2 diabetes patients based on multicenter prospective real-world data.

BACKGROUND: To investigate the different efficacies of glycemic control between basal and premixed insulin in participants with type 2 diabetes (T2DM) when non-insulin medications fail to reach treatment targets. METHODS: This was a prospective, large-scale, real-world study at 10 diabetes centers in China. Between June 2017 and June 2021, we enrolled 1104 T2DM participants initiated with either once-daily basal insulin or twice-daily premixed insulin when the glycosylated hemoglobin (HbA1c) control target was not met after at least two non-insulin agents were administered. A Cox proportional hazards regression model adjusting for multiple influencing factors was performed to compare the different effects of basal and premixed insulin on reaching the HbA1c control target. RESULTS: At baseline, basal insulin (57.3%) was prescribed more frequently than premixed insulin (42.7%). Patients with a higher body mass index (BMI) or higher HbA1c levels were more likely to receive premixed insulin than basal insulin (both p < 0.001). After a median follow-up of 12.0 months, compared to those with premixed insulin, the hazard ratio for reaching the HbA1c target to those with basal insulin was 1.10 (95% CI, 0.92-1.31; p = 0.29) after adjustment, and less weight gain was observed in those with basal insulin than with premixed insulin (percentage change of BMI from baseline -0.37[5.50]% vs 3.40[6.73]%, p < 0.0001). CONCLUSIONS: In this real-world study, once-daily basal insulin was more frequently prescribed and had similar glycemic control effects but less weight gain compared with twice-daily premixed insulin when used as initiation therapy for those in whom glycemic control with non-insulin medications failed.

The neuroprotective effect and RNA-sequence analysis of postconditioning on the ischemic stroke with diabetes mellitus tree shrew model.

INTRODUCTION: Patients with comorbidity of ischemic stroke (IS) and diabetes mellitus (DM) show poor neurological functional recovery, and ischemic postconditioning (IPOC) should be considered a powerful neuroprotective method for IS. However, whether it should be introduced for patients with IS and DM remains controversial. This study established a DM with IS (DMIS) tree shrew model, which was intervened by IPOC to assess its neuroprotective effects and also to analyze the relevant mechanism by RNA-sequence and bioinformatics analysis. METHODS: Fifty-four tree shrews were randomly divided into a sham operation control group, a DMIS group, and an IPOC group (DMIS model), with 18 tree shrews per group. Triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM), and RNA-sequence analysis were performed to assess the IPOC effect. RESULTS: IPOC reduced infarct size and reduced nerve cell injury in IS tree shrews with DM. RNA-seq analysis showed that IPOC significantly increased the expression of the homeobox protein SIX3, while downregulating the expression of HLA class II histocompatibility antigens DQ beta 1 chain, CAS1 domain-containing protein 1, and cytokine receptor-like factor 2. The most downregulated signaling pathways include the NF-κB signaling pathway, TNF signaling pathway, and Fc gamma R-mediated phagocytosis. CONCLUSIONS: IPOCs have a neuroprotective effect in a DMIS animal model that reduces infarct size and nerve cell injury. This mechanism might be related to reducing inflammation and stress responses that decreases the activity of TNF and NF-κB signaling pathways.

RNA-seq analysis of ischemia stroke and normal brain in a tree shrew model with or without type 2 diabetes mellitus.

Nowadays, similar strategies have been used for the treatment and prevention of acute stroke in both diabetes mellitus (DM) and non-DM populations. These strategies were analyzed to provide an experimental basis for the clinical prevention and treatment of stroke in patients both with and without DM. Tree shrews were randomly divided into control, DM, ischemic stroke (IS), and DMIS groups with 18 animals in each group. Serum biochemical indicators were used to assess metabolic status. Neural tissue damage was determined using triphenyl tetrazolium chloride staining, H-E staining, and electron microscopy. Differential gene expression of neural tissue between the DM and control groups and the IS and DMIS groups was measured using RNA-seq analysis. The serum glucose levels of the DM and DMIS groups were significantly higher than other groups. In the DMIS group, the infarct size was significantly larger than in the IS group (19.56 ± 1.25%), with a more obvious abnormal ultrastructure of neural cells. RNA-seq analysis showed that the expression of IL-8, C-C motif chemokine 2 (CCL2), and alpha-1-antichymotrypsin was significantly higher in the DM group than in the control group. The CCL7, ATP-binding cassette sub-family A member 12, and adhesion G protein-coupled receptor E2 levels were significantly higher in the DMIS group than in the IS group. For the prevention and treatment of stroke in patients with DM, reducing the inflammatory state of the nervous system may reduce the incidence of stroke and improve the prognosis of neurological function after IS.

Postoperative Vomiting Following Laparoscopic Cholecystectomy Is Associated with Intraoperative Fluid Administration: A Retrospective Cohort Study.

Potential risk factors for postoperative vomiting (POV) are important for daily anesthesia practice. To identify the risk factors associated with POV we retrospectively reviewed 553 adult patients who underwent scheduled simple laparoscopic cholecystectomy under sevoflurane-based general anesthesia between January and December 2018. Patients who experienced POV were predominantly women, had lower body weight, and higher ASA (American Society of Anesthesiologists) physical status. The POV group showed female sex predominance, lower body weight, and higher ASA physical status, with a significant difference when compared with the non-POV group. In univariate analysis, female sex and Apfel scores of 2, 3, and 4 were associated with a higher POV incidence. Age > 70 years, higher body weight, and ASA physical status III were associated with a lower POV incidence. In multivariate logistic regression, sex, age, Apfel score, and intraoperative crystalloid infusion rate were POV predictive factors. Receiver operating characteristic analysis showed a negative association between the intraoperative crystalloid infusion rate and POV occurrence with an area under the curve of 0.73 (p = 0.001). The cutoff intraoperative crystalloid infusion rate was 2 mL/kg/h with 82% sensitivity and 49% specificity (≥2 mL/kg/h was associated with a lower POV incidence vs. <2 mL/kg/h (OR, 95% CI; 0.52 [0.33-0.83])). To decrease POV in these patients, identifying high-risk factors and an intraoperative crystalloid administration of ≥2 mL/kg/h should be considered in patients undergoing LC under sevoflurane-based general anesthesia.

Celecoxib ameliorates diabetic neuropathy by decreasing apoptosis and oxidative stress in dorsal root ganglion neurons via the miR-155/COX-2 axis.

Celecoxib (CXB) is the only clinical cyclooxygenase-2 (COX-2) inhibitor. Oral administration of CXB in experimental diabetic mice effectively relieved the symptoms of diabetic neuropathy (DN); however, the molecular mechanism remains unclear. The present study aimed to investigate the potential molecular mechanisms of CXB in the treatment of DN. An in vitro cellular model of DN was produced by stimulating dorsal root ganglion (DRG) neurons with high glucose. Cell viability and apoptosis were assessed by Cell Counting Kit-8 assays and flow cytometry, respectively. Reactive oxygen species (ROS) kits, ELISA kits and western blotting were used to determine oxidative cellular damage. The expression level of microRNA (miR)-155 was analyzed by reverse transcription-quantitative PCR. The starBase database and dual-luciferase assays were performed to predict and determine the interaction between miR-155 and COX-2. Protein expression of neurotrophic factors, oxidative stress-related proteins and COX-2 were analyzed by western blotting. Incubation with high glucose led to a decrease in DRG neuron cell viability, facilitated apoptosis, downregulated NGF and BDNF expression, increased ROS and MDA generation and decreased SOD activity. Treatment with CXB significantly protected DRG neurons against high glucose-evoked damage. CXB promoted the expression of miR-155 and COX-2 was revealed to be a direct target of miR-155. Inhibition of COX-2 enhanced the protective effect of CXB on DRG neurons and that treatment with an miR-155 inhibitor partially rescued this effect. The present study demonstrated the involvement of the miR-155/COX-2 axis in the protective effect of CXB against high glucose-induced DN.

Risk Factors of Postoperative Vomiting in the Eye of "Real-World Evidence"-Modifiable and Clinical Setting-Dependent Risk Factors in Surgical Trauma Patients.

Numerous studies on postoperative nausea and vomiting (PONV) have been carried out since the early days of contemporary surgery. The incidence of PONV has been greatly reduced in recent years and new drugs for PONV keep evolving in the market; however, a substantial number of patients are still under the threat of PONV. Female gender, non-smokers, a history of PONV/motion sickness, and postoperative opioid use are four well-recognized risk factors of PONV. Many potential risk factors reported in previous studies were not consistently presented as predictors for PONV. Two questions then arise; are risk factors clinical setting dependent and are risk factors modifiable? We attempted to answer the questions through a comprehensive review of perioperative records of surgical patients from the Trauma Department of our hospital. As nausea is subjective and no standard is applicable for its measurement, postoperative vomiting (POV) was used as an endpoint in this study. To the best of our knowledge, this is the first study to address the POV issue in surgical trauma patients. A total of 855 patients were enrolled in this study after excluding age below 20 years old, total intravenous anesthesia, desflurane anesthesia, or records with missing data. Our results showed that female gender (OR 4.89) is the strongest predicting factor, followed by a less potent predicting factor-more intraoperative opioid consumption (OR 1.07)-which favor more POV. More intraoperative crystalloid supply (OR 0.71) and a higher body weight (OR 0.9) favor less POV. Other potential risk factors did not reach statistical significance in this study as independent risk factors. Our results also showed that when the intraoperative crystalloid infusion rate is greater than 4 mL/kg/h (OR 0.20), it favors a lower rate of POV; when intraoperative opioid consumption is greater than 12 mg morphine equivalents, MME (OR 1.87), it favors a higher rate of POV. We concluded that dominance of any independent risk factor over other risk factors depends on how individual factors interact with the clinical setting. Some risk factors could be modified, and a cut-off value could be derived to facilitate a better plan for POV prevention.

Artificial intelligence-enabled screening for diabetic retinopathy: a real-world, multicenter and prospective study.

INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.

A novel algorithm to predict oxygen desaturation in sedated patients with obstructive sleep apnea utilizing polysomnography: A STROBE-compliant article.

This retrospective study aimed at identifying the predictors of oxygen desaturation (OD) (i.e., SpO2 < 95%) in patients with obstructive sleep apnea (OSA) requiring deep sedation and developing an algorithm to predict OD.We studied 66 OSA patients undergoing propofol-induced deep sedation for drug-induced sleep endoscopy (DISE). The patients were divided into prediction (n = 35) and validation (n = 31) groups. Patient characteristics and polysomnographic parameters were analyzed with receiver operating characteristic curve and Chi-squared test to identify significant predictors of OD for developing an algorithm in the prediction group. The predictive accuracy, sensitivity, positive predictive value, and negative predictive value of the algorithm were determined in the validation group.Six polysomnographic predictors of OD were identified, including Apnea-Hypopnea Index of total sleep time (AHI-TST), AHI at the stage of rapid eye movement (AHI-REM), percentage of time with oxygen saturation <90% (mO2 < 90%), average SpO2, lowest SpO2, and desaturation index. Stepwise multiple logistic regression analysis demonstrated that low average SpO2 (<95.05%) and high AHI-REM (>16.5 events/h) were independent predictors of OD. The algorithm thus developed showed that patients with an average SpO2 < 95.05% and those with an average SpO2 ≥ 95.05% together with an AHI-REM > 16.5 events/h would be at risk of OD under sedation. The predictive accuracy, sensitivity, positive predictive value, and negative predictive value were 84%, 100%, 83%, 100%, respectively.For patients with OSA, average SpO2 and AHI-REM may enable clinicians to predict the occurrence of oxygen desaturation under deep sedation. Future large-scale studies are needed to validate the findings.

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia.

Ischemic postconditioning (PC) is proved to efficiently protect diabetic patients with acute myocardial infarction from ischemia-reperfusion injury. We aimed to explore the protective roles of ischemic PC on diabetic retinopathy in tree shrews with diabetic cerebral ischemia. A diabetic tree shrew model was established through high-fat diet feeding combined with streptozotocin (STZ) injection, while cortical thrombotic cerebral ischemia was induced photochemically. Tree shrews were divided into the normal control group, sham operation group, diabetes mellitus group, diabetes mellitus+cerebral ischemia group, and diabetes mellitus+cerebral ischemia+PC group (in which the tree shrews with diabetic cerebral ischemia were treated with ischemic PC). H&E staining was used to examine the pathological changes in the retina, and immunohistochemistry was performed to determine the retinal expression of VEGF (vascular endothelial growth factor). The modeling resulted in 77% tree shrews with diabetes. Ischemic PC reduced the blood glucose levels in the tree shrews with diabetic cerebral ischemia. Tree shrews with diabetes had thinned retina with disordered structures, and these pathological changes were aggravated after cerebral ischemia. The retinopathy was alleviated after ischemic PC. Retina expression of VEGF was mainly distributed in the ganglion cell layer in tree shrews. Diabetes and cerebral ischemia increased retinal VEGF expression in a step-wise manner, while additional ischemic PC reduced retinal VEGF expression. Therefore, ischemic PC effectively alleviates retinopathy in tree shrews with diabetic cerebral ischemia, and this effect is associated with reduced retinal VEGF expression.

Composite Hydrogel Modified by IGF-1C Domain Improves Stem Cell Therapy for Limb Ischemia.

Stem cell treatment for critical limb ischemia yields a limited therapeutic effect due to cell loss and dysfunction caused by local ischemic environment. Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell fate via mimicking the components of stem cell niche. Herein, we prepared a bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized with C domain peptide of insulin-like growth factor 1 (IGF-1C) and examined whether this hydrogel could augment stem cell survival and therapeutic potential. Our results showed that IGF-1C-modified hydrogel increased in vitro viability and proangiogenic activity of adipose-derived stromal cells (ADSCs). Moreover, cotransplantation of hydrogel and ADSCs into ischemic hind limbs of mice effectively ameliorated blood perfusion and muscle regeneration, leading to superior limb salvage. These therapeutic effects can be ascribed to improved ADSC retention, angiopoientin-1 secretion, and neovascularization, as well as reduced inflammatory cell infiltration. Additionally, hydrogel enhanced antifibrotic activity of ADSCs, as evidenced by decreased collagen accumulation at late stage. Together, our findings indicate that composite hydrogel modified by IGF-1C could promote survival and proangiogenic capacity of ADSCs and thereby represents a feasible option for cell-based treatment for critical limb ischemia.

A macroporous heparin-releasing silk fibroin scaffold improves islet transplantation outcome by promoting islet revascularisation and survival.

Islet transplantation is considered the most promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical islet transplantation is limited by long-term graft dysfunction and attrition. We have investigated the therapeutic potential of a silk fibroin macroporous (SF) scaffold for syngeneic islet transplantation in diabetic mice. The SF scaffold was prepared via lyophilisation, which enables incorporation of active compounds including cytokines, peptide and growth factors without compromising their biological activity. For the present study, a heparin-releasing SF scaffold (H-SF) in order to evaluate the versatility of the SF scaffold for biological functionalisation. Islets were then co-transplanted with H-SF or SF scaffolds in the epididymal fat pad of diabetic mice. Mice from both H-SF and SF groups achieved 100% euglycaemia, which was maintained for 1year. More importantly, the H-SF-islets co-transplantation led to more rapid reversal of hyperglycaemia, complete normalisation of glucose responsiveness and lower long-term blood glucose levels. This superior transplantation outcome is attributable to H-SF-facilitated islet revascularisation and cell proliferation since significant increase of islet endocrine and endothelial cells proliferation was shown in grafts retrieved from H-SF-islets co-transplanted mice. Better intra-islet vascular reformation was also evident, accompanied by VEGF upregulation. In addition, when H-SF was co-transplanted with islets extracted from vegfr2-luc transgenic mice in vivo, sustained elevation of bioluminescent signal that corresponds to vegfr2 expression was collected, implicating a role of heparin-dependent activation of endogenous VEGF/VEGFR2 pathway in promoting islet revascularisation and proliferation. In summary, the SF scaffolds provide an open platform as scaffold development for islet transplantation. Furthermore, given the pro-angiogenic, pro-survival and minimal post-transplantation inflammatory reactions of H-SF, our data also support the feasibility of clinical implementation of H-SF to improve islet transplantation outcome. STATEMENT OF SIGNIFICANCE: 1) The silk fibroin scaffold presented in the present study provides an open platform for scaffold development in islet transplantation, with heparinisation as an example. 2) Both heparin and silk fibroin have been used clinically. The excellent in vivo therapeutic outcome reported here may therefore be clinically relevant and provide valuable insights for bench to bed translation. 3) Compared to conventional clinical islet transplantation, during which islets are injected via the hepatic portal vein, the physical/mechanical properties of silk fibroin scaffolds create a more accessible transplantation site (i.e., within fat pad), which significantly reduces discomfort. 4) Islet implantation into the fat pad also avoids an instant blood mediated inflammatory response, which occurs upon contact of islet with recipient's blood during intraportal injection, and prolongs survival and function of implanted islets.

Differences in the performance of PCL-based vascular grafts as abdominal aorta substitutes in healthy and diabetic rats.

Great progress has been made in the field of vascular tissue engineering, with some artificial vascular grafts already exhibiting promising outcomes in animal models. However, these studies were mostly conducted using healthy animals, which are not representative of actual clinical demands. Indeed, patients who require artificial vascular graft implantation are often accompanied by other comorbidities, such as hyperlipidaemia, hypertension and diabetes which should also be taken into consideration when assessing the potential of vascular grafts that are intended for clinical applications. In the present study, we established a rat model with type 2 diabetes (T2D) for performance evaluation of an electrospun PCL vascular graft. Our data showed that rats with T2D had elevated incidents of adverse event rates, including exacerbated platelet adhesion, inflammation, early calcification and impaired regeneration compared to the non-diabetic controls. Thus, we report that T2D exacerbates the regeneration process after in vivo implantation of vascular grafts. More advanced grafts are in demand for clinical use in patients with clinical complications such as T2D.