CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2.

OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.

Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis.

AIMS: To evaluate the impact of a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide (TZP), and its potential dose-response effect, on heart rate. METHODS: Articles were searched from PubMed, Web of Science, Embase, Cochrane Library, and clinical trials registries (ClinicalTrials.gov) databases. Randomized controlled trials (RCTs) comparing TZP at doses of 5, 10 and 15 mg in adults with type 2 diabetes were included. Six study arms were summarized from original research (TZP 5, 10 and 15 mg, GLP-1 receptor agonists [GLP-1RAs], insulin, placebo). The GLP-1RA and non-GLP-1RA groups were combined to form a control group. Two reviewers independently extracted data and assessed the quality of each study. Mean differences (MDs) were calculated as effect estimates for continuous outcomes. Pairwise meta-analyses and network meta-analyses were conducted. The study protocol was prospectively registered (PROSPERO ID: CRD42023418551). RESULTS: Eight articles were included in this systematic review and meta-analysis. The mean baseline heart rate ranged from 65.2 to 75.7 beats per minute. Pairwise meta-analysis showed that, compared with combined the control group, there were significantly greater increases in heart rates in the TZP group (MD 1.82, 95% confidence interval [CI] 0.75, 2.89). Similar significant rises were identified when comparing TZP with GLP-1RAs and non-GLP-1RAs (GLP-1 RAs: MD 2.29, 95% CI 1.00, 3.59; non-GLP-1RAs: MD 1.58, 95% CI 0.26, 2.91). TZP 5 mg was associated with smaller increases in heart rates compared to TZP 10 mg and TZP 15 mg (TZP 10 mg: MD -0.97, 95% CI -1.79, -0.14; TZP 15 mg: MD -2.57, 95% CI -3.79, -1.35). TZP 10 mg increased heart rate less than TZP 15 mg (MD -1.5, 95% CI -2.38, -0.82). Network meta-analysis indicated that TZP 15 mg was associated with significant increases in heart rate compared with TZP 5 mg (MD 2.53, 95% CI 1.43, 3.62), TZP 10 mg (MD 1.44, 95% CI 0.35, 2.53), GLP-1RAs (MD 3.46, 95% CI 1.67, 5.25), insulin (MD 2.86, 95% CI 1.32, 4.41) and placebo (MD 2.96, 95% CI 1.36, 4.57). CONCLUSIONS: Our study showed not only that there was a greater increase in heart rate in the TZP group than in the control, GLP-1RA and non-GLP-1RA groups, but also that the 15-mg dose of TZP had the strongest impact on increasing heart rates compared with the other five inventions, with a TZP dose-response impact on heart rate. Further research on the effects of TZP treatment-related increases in heart rate is required.

Leukocyte telomere length independently predicts hyperuricemia risk in a longitudinal study of the Chinese population.

BACKGROUND AND AIMS: Leukocyte telomere length (LTL) has been correlated with uric acid levels, although results are inconsistent, and prospective studies are lacking. In this longitudinal, prospective cohort study, we aimed to assess whether a shorter LTL predicts the risk of hyperuricemia. METHODS AND RESULTS: We conducted a longitudinal study in a Chinese cohort of 599 participants. Of these, 266 participants completed a 5.9-year follow-up from June 2014 to December 2021. LTL was assessed at baseline using real-time polymerase chain reaction. Hyperuricemia was defined as serum uric acid ≥420 mmol/L according to Chinese guidelines for diagnosis and treatment of hyperuricemia and gout. Participants who had developed hyperuricemia during follow-up (n = 17) had shorter LTL at baseline. Baseline LTL was independently associated with the development of hyperuricemia at follow-up after adjusting for conventional hyperuricemia risk factors (odds ratio [OR] 2.347 [95% confidence interval [CI] 1.123, 4.906]; P = 0.023). After grouping according to LTL tertiles, the incidence of hyperuricemia was 18.334-fold higher for the first than for the third tertile (OR 18.334 [95%CI 1.786, 191.272]; P = 0.014, P for trend = 0.050). CONCLUSION: Our findings in a prospective cohort suggest that LTL could predict hyperuricemia risk, which might inform the timely prevention and treatment of hyperuricemia.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy.

Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events.Results The study population consisted of 24 case of insulinoma patients, 7 males and 17 females, aged 46.08 ± 14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51 ± 3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 [interquartile range (IQR): 2.50-2.90] mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P = 0.000]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P = 0.000). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P = 0.000], but only one patient who continued to receive RCS for over 4 weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Mouse Abdominal Aortic Aneurysm Model Induced by Periarterial Incubation of Papain.

For decades, numerous experimental animal models have been developed to examine the pathophysiologic mechanisms and potential treatments for abdominal aortic aneurysms (AAAs) in diverse species with varying chemical or surgical approaches. This study aimed to create an AAA mouse model by the periarterial incubation with papain, which can mimic human AAA with advantages such as simplicity, convenience, and high efficiency. Eighty C57BL/6J male mice were randomly assigned to 1 of the 4 groups: papain (1.0 or 2.0 mg), porcine pancreatic elastase, and phosphate-buffered solution. The aortic segment was wrapped for 20 minutes, and the diameter was measured using ultrasound preoperatively and postoperative days 7 and 14. Then, the mice were killed for histomorphometric and immunohistochemical analyses. According to ultrasound measurements and histomorphometric analyses, on postoperative day 7, 65% of mice in the 1.0-mg papain group and 60% of mice in the 2.0-mg papain group developed AAA. In both papain groups, 100% of mice developed AAA, and 65% of mice in the porcine pancreatic elastase group developed AAA on postoperative day 14. Furthermore, hematoxylin/eosin, elastin van Gieson, and Masson staining of tissues from the papain group revealed thickened media and intimal hyperplasia, collagen sediments, and elastin destruction, indicating that AAA histochemical alteration was similar to that of humans. In addition, the immunohistochemical analysis was conducted to detect infiltrated inflammatory cells, such as macrophages and leukocytes, in the aortic wall and hyperplasic adventitia. The expression of matrix metalloproteinase 2 and 9 was significantly upregulated in papain and human AAA tissues. Periarterial incubation with 1.0 mg of papain for 20 minutes can successfully create an experimental AAA model in mice for 14 days, which can be used to explore the mechanism and treatment of human AAA.

Controllable Fabrication of Highly Uniform Sub-10 nm Nanoparticles from Spontaneous Confined Nanoemulsification.

Sub-10 nm nanoparticles are known to exhibit extraordinary size-dependent properties for wide applications. Many approaches have been developed for synthesizing sub-10 nm inorganic nanoparticles, but the fabrication of sub-10 nm polymeric nanoparticles is still challenging. Here, a scalable, spontaneous confined nanoemulsification strategy that produces uniform sub-10 nm nanodroplets for template synthesis of sub-10 nm polymeric nanoparticles is proposed. This strategy introduces a high-concentration interfacial reaction to create overpopulated surfactants that are insoluble at the droplet surface. These overpopulated surfactants act as barriers, resulting in highly accumulated surfactants inside the droplet via a confined reaction. These surfactants exhibit significantly changed packing geometry, solubility, and interfacial activity to enhance the molecular-level impact on interfacial instability for creating sub-10 nm nanoemulsions via self-burst nanoemulsification. Using the nanodroplets as templates, the fabrication of uniform sub-10 nm polymeric nanoparticles, as small as 3.5 nm, made from biocompatible polymers and capable of efficient drug encapsulation is demonstrated. This work opens up brand-new opportunities to easily create sub-10 nm nanoemulsions and advanced ultrasmall functional nanoparticles.

Tumor necrosis factor-alpha mediates the negative association between telomere length and kidney dysfunction.

Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 54.3±9.7 years; follow-up period, 5.9±1.1 years), 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function (OR=1.83 [95% CI 1.07, 3.27] per 1SD, P=0.03; OR=7.57 [95% CI 1.25, 145.88] for Q1 vs. Q4, P for trend=0.031); and the composite endpoint of kidney dysfunction (OR=1.37 [95% CI 0.97, 1.96] per 1SD, borderline positive P=0.072; OR=2.96[95% CI 1.15, 8.2] for Q1 vs. Q4, P for trend=0.036). The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function (direct effect: ß=0.046 95%CI [0.006, 0.090],P=0.02; indirect effect: ß=0.013 95%CI [0.003, 0.020]), and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension (OR=49.07[3.72,211.12] vs.1.32[0.69,2.58] per 1SD, P for interaction=0.045;OR=3.10 [1.48, 7.52] vs.1.08[0.92,1.63] per 1SD, P for interaction=0.036). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction.

Liraglutide Attenuates Hepatic Oxidative Stress, Inflammation, and Apoptosis in Streptozotocin-Induced Diabetic Mice by Modulating the Wnt/ß-Catenin Signaling Pathway.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus and also has hepatoprotective effects. However, the role of liraglutide treatment on liver injury in a mouse model of type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) and its underlying mechanisms remain to be elucidated. In the present study, diabetes was initiated in experimental animals by single-dose intraperitoneal inoculation of STZ. Forty female C57BL/6J mice were equally assigned into five groups: diabetic group, insulin+diabetic group, liraglutide+diabetic group, insulin+liraglutide+diabetic group, and control group for eight weeks. Diabetic mice exhibited a significantly elevated blood glucose level and decreased body weight, and morphological changes of increased steatosis and apoptosis were observed in the liver compared with the control. Furthermore, a significant increase in the levels of malondialdehyde and inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1ß (IL-1ß) and the proapoptotic proteins caspase-3 and Bax were observed in the livers of diabetic mice, together with marked increases in antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as antiapoptotic protein Bcl-2, all of which were significantly mitigated by treatment with liraglutide, insulin, and their combinations. Interestingly, liraglutide monotherapy showed better efficacy in ameliorating liver injury in T1DM mice than insulin monotherapy, similar to the combined drug therapy. Furthermore, the expression of Wnt/ß-catenin signaling pathway-associated molecules was upregulated in the liver of mice treated with liraglutide or insulin. The results of the present study suggested that liraglutide improves T1DM-induced liver injury and may have important implications for the treatment of nonalcoholic fatty liver disease (NAFLD) in patients with T1DM.

Impact of percutaneous coronary intervention on renal function in patients with coronary heart disease.

The relationship between cardiac and renal function is complicated. The impact of percutaneous coronary intervention (PCI) on renal function in patients with coronary artery disease is still unclear. The current study sought to assess renal function change, including the time course of renal function, after elective PCI in patients with improved renal function and to identify renal function predictors of major adverse cardiovascular events. We examined data from 1572 CHD patients who had coronary angiography (CAG) or PCI in this retrospective cohort study. Patients receiving elective PCI (n=1240) and CAG (n=332) between January 2013 and December 2018 were included. Pre-PCI and procedural variables associated with post-PCI eGFR, change in renal function after post-PCI follow-up, and post-PCI eGFR association with major adverse cardiovascular events were investigated. Following the procedure, 88.7 percent of PCI group patients had unchanged or improved renal function. The treatment of PCI was found to independently correlate with IRF following coronary angiography in an analysis of patients undergoing PCI [OR 4.561 (95% CI:2 .556-8.139); p<0.001]. The area under the receiver operating characteristic (ROC) curve is 0.763 (model with the treatment of PCI). Improved renal function (IRF) and stable renal function were both associated with a lower risk of a major cardiovascular event.

[Serum Uric Acid Level and Its Influencing Factors in Patients with Diabetes Insipidus].

Objective To investigate the level of serum uric acid in patients with diabetes insipidus (DI),summarize the clinical characteristics of central diabetes insipidus (CDI) patients with hyperuricemia (HUA),and analyze the factors affecting the level of serum uric acid in the patients with CDI. Methods The clinical data of DI patients admitted to Peking Union Medical College Hospital from 2018 to 2021 were retrospectively analyzed.The patients were assigned into a child and adolescent group (≤ 18 years old) and an adult group (>18 years old) according to their ages.The demographic and biochemical data between two groups of patients with and without HUA were compared.Spearman correlation analysis and multiple linear regression analysis were performed to analyze the correlations between serum uric acid level and other factors. Results Among the 420 DI patients,411 patients had CDI (97.9%),including 189 patients with HUA (46.0%).Thirteen (6.9%) out of the 189 CDI patients with HUA presented the disappearance of thirst.The prevalence of HUA in children and adolescents was higher than that in adults (χ2=4.193,P=0.041).The level of serum uric acid in the CDI patients with HUA and disappearance of thirst was higher than those without disappearance of thirst (U=2.593,P=0.010).The multiple linear regression predicted serum creatinine (ß=0.472,95%CI=2.451-4.381,P<0.001) and body mass index (ß=0.387,95%CI=6.18-12.874,P<0.001) as the independent risk factors of serum uric acid level increment in children and adolescents,while serum creatinine (ß=0.361,95%CI=1.016-1.785,P<0.001),body mass index (ß=0.208,95%CI=2.321-6.702,P<0.001),triglyceride (ß=0.268,95%CI=12.936-28.840,P<0.001),and total cholesterol (ß=0.129,95%CI=2.708-22.250,P=0.013) were the independent risk factors in adults. Conclusions The patients with CDI were more likely to have HUA,and the prevalence of HUA in children and adolescents was higher than that in adults.Body mass index,serum creatinine,triglyceride,total cholesterol,and disappearance of thirst were the risk factors for the increased level of serum uric acid in CDI patients.

Improvement in glucose metabolism in adult male offspring of maternal mice fed diets supplemented with inulin via regulation of the hepatic long noncoding RNA profile.

Maternal overnutrition during pregnancy and lactation is an important risk factor for the later development of metabolic disease, especially diabetes, among mothers and their offspring. As a fructan-type plant polysaccharide, inulin has prebiotic functions and is widely used as a natural antidiabetic supplement. However, to date, the mechanism of maternal inulin treatment in the livers of offspring has not been addressed, especially with respect to long noncoding RNAs (lncRNAs). In this study, female C57BL6/J mice were fed either a high-fat diet (HFD) with or without inulin supplementation or a standard rodent diet (SD) during gestation and lactation. After the offspring were weaned, they were fed a SD for 5 weeks. At 8 weeks of age, the glucose metabolism indexes of the offspring were assessed, and their livers were collected to assay lncRNA and mRNA profiles to investigate the effects of early maternal inulin intervention on offspring. Our results indicate that male offspring from HFD-fed dams displayed glucose intolerance and an insulin resistance phenotype at 8 weeks of age. Early maternal inulin intervention improved glucose metabolism in male offspring of mothers fed a HFD during gestation and lactation. The lncRNA and mRNA profile data revealed that compared with the offspring from HFD dams, offspring from the early inulin intervention dams had 99 differentially expressed hepatic lncRNAs and 529 differentially expressed mRNAs. The differentially expressed lncRNA-mRNA coexpression analysis demonstrated that early maternal inulin intervention may change hepatic lncRNA expression in offspring; there lncRNAs are involved in metabolic pathways and the AMP-activated protein kinase signaling pathway. Importantly, the early maternal inulin intervention alleviated glucose metabolism by inhibiting the lncRNA Serpina4-ps1/let-7b-5p/Ppargc1a as a competing endogenous RNA in male offspring.

Sirt6 regulates autophagy in AGE-treated endothelial cells via KLF4.

BACKGROUND AND AIMS: High glucose and its byproducts are important factors causing dysfunction of endothelial cells. Autophagy is critical for endothelial cellular homeostasis. However, the specific molecular mechanism of how autophagy is regulated in endothelial cells under high-glucose condition remains unknown. We aim to explore the role Sirt6 plays in regulating autophagy in AGE-treated endothelial cells and how this function is exerted via KLF4. METHODS AND RESULTS: Our results indicate that autophagy level increased in AGE-treated endothelial cells alongside with higher Sirt6 and KLF4 expression level. What's more, knock-in of Sirt6 by adenovirus led to augmented autophagy level while knockdown of Sirt6 led to the opposite. We also verified that Sirt6 affected KLF4 expression positively but KLF4 didn't influence Sirt6 expression level while knocking out of KLF4 impaired Sirt6-enhanced autophagy. Finally we found that STZ-induced diabetic mice showed more autophagosomes in endothelium and Sirt6 knockdown by adeno-associated virus reduced the number of autophagosomes. Knockdown of Sirt6 also caused impaired endothelium integrity but echocardiography indicated there were no significant functional differences. CONCLUSION: Our research reveals more about how Sirt6 regulates autophagy in endothelial cells under high-glucose simulated condition and provides further insight into the relationships between Sirt6 and KLF4.

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Coronavirus Infection.

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

A Clinical Prediction Model to Distinguish Maturity-Onset Diabetes of the Young From Type 1 and Type 2 Diabetes in the Chinese Population.

OBJECTIVE: Genetic detection for the diagnosis of maturity-onset diabetes of the young (MODY) in China has low sensitivity and specificity. Better gene detection is urgently needed to distinguish testing subjects. We proposed to use numerous and weighted clinical traits as key indicators for reasonable genetic testing to predict the probability of MODY in the Chinese population. METHODS: We created a prediction model based on data from 306 patients, including 140 patients with MODY, 84 patients with type 1 diabetes (T1D), and 82 patients with type 2 diabetes (T2D). This model was evaluated using receiver operating characteristic curves. RESULTS: Compared with patients with T1D, patients with MODY had higher C-peptide levels and negative antibodies, and most patients with MODY had a family history of diabetes. Different from T2D, MODY was characterized by lower body mass index and younger diagnostic age. A clinical prediction model was established to define the comprehensive probability of MODY by a weighted consolidation of the most distinguishing features, and the model showed excellent discrimination (areas under the curve of 0.916 in MODY vs T1D and 0.942 in MODY vs T2D). Further, high-sensitivity C-reactive protein, glycated hemoglobin A1c, 2-h postprandial glucose, and triglyceride were used as indicators for glucokinase-MODY, while triglyceride, high-sensitivity C-reactive protein, and hepatocellular adenoma were used as indicators for hepatocyte nuclear factor 1-α MODY. CONCLUSION: We developed a practical prediction model that could predict the probability of MODY and provide information to identify glucokinase-MODY and hepatocyte nuclear factor 1-α MODY. These results provide an advanced and more reasonable process to identify the most appropriate patients for genetic testing.

Synchronous distance education vs traditional education for health science students: A systematic review and meta-analysis.

CONTEXT: Synchronous distance education (SDE) has been widely used for health science students in recent years. This study examined the effectiveness and acceptance of SDE compared with traditional education for health science students and explored the potential moderators that could impact the pooled results. METHODS: A systematic review and meta-analysis was conducted of randomised controlled trials (RCTs) from January 2000 to March 2020 searched on nine electronic databases, including Web of Science, PubMed, Cochrane Library, Scopus, EMBASE, CINAHL, ERIC, PsycINFO, and ProQuest Dissertations and Theses. The outcomes measured were knowledge, skills with objective assessments and overall satisfaction with subjective evaluations. The pooled results were calculated using random-model effects, and moderators were explored through meta-regression. RESULTS: A total of seven RCTs with 594 participants were included. At the post-test level, the pooled effect size of knowledge acquisitions (SMD 0.12, 95% CI -0.07-0.32) showed insignificant difference between the SDE and traditional education groups (P = .207), with low heterogeneity (I2  = 17.6%). Subgroup analyses observed no factors that significantly impacted the pooled results of knowledge acquisition at the post-test levels (P for interaction > 0.05). Knowledge gains from pretest to post-test in SDE groups also did not differ significantly between groups (SMD 0.15, 95% CI -0.22-0.53; P = .428). The pooled effect size of skills (SMD 0.02, 95% CI -0.24-0.28; P = .735) was similarly insignificant. The pooled effect size of overall satisfaction (SMD 0.60, 95% CI 0.38-0.83; P < .001) significantly favoured SDE over traditional education. Incorporating two-group studies without randomisations did not significantly change the overall results of knowledge acquisition at the post-test level (SMD -0.002, 95% CI -0.11-0.10; P = .994), with moderate heterogeneity (I2  = 61.9%). CONCLUSIONS: Synchronous distance education was not significantly different from traditional education in effectiveness and had higher satisfaction ratings. Our findings might provide indications for adoptions of online remote education in health science education centres.

[Network Meta-analysis of Chinese patent medicine in treatment of unstable angina pectoris].

Network Meta-analysis was used to compare the efficacy and safety of Chinese patent medicines in the treatment of unstable angina pectoris. PubMed, Cochrane Library, CNKI, Wanfang, VIP and other databases were retrieved by computers from the establishment of the databases to June 2020. Randomized controlled trials(RCTs) of Chinese patent medicines for the treatment of unstable angina pectoris were collected. Two investigators independently screened out the literatures, and extracted data according to the inclusion and exclusion criteria. The quality of the included RCTs was evaluated according to the bias risk assessment tool recommended by the Cochrane System Reviewer Manual, and the Stata 13.0 software was used for data analysis and mapping. Through screening, 28 eligible studies were finally included, with the sample size of 2 885 cases, involving 8 Chinese patent medicines. The results of the network Meta-analysis showed that in terms of total effective rate for angina symptom improvement, the order was as follows: Shenshao Capsules > Naoxintong Capsules > Ginkgo Ketone Ester Dripping Pills > Compound Danshen Dripping Pills > Ginkgo Leaf Tablets > Shexiang Baoxin Pills > Tongxinluo Capsules > Yindan Xinnaotong Soft Capsules; in terms of total effective rate for ECG curative effect, the order was as follows: Ginkgo Ketone Ester Dripping Pills>Compound Danshen Dripping Pills > Tongxinluo Capsules > Shenshao Capsules > Shexiang Baoxin Pills > Yindan Xinnaotong Soft Capsules; in terms of hypersensitivity-C-reactive protein curative effect, the order was as follows: Tongxinluo Capsules > Shenshao Capsules > Ginkgo Leaf Tablets>Compound Danshen Dropping Pills> Shexiang Baoxin Pills > Naoxintong Capsules > Yindan Xinnaotong Soft Capsules > Ginkgo Ketone Ester Dropping Pills. Chinese patent medicine combined with conventional therapy can improve the clinical efficacy of unstable angina pectoris. Due to the differences in the quantity and quality of the included studies, the order results of Chinese patent medicines need to be further verified.

Triglyceride is independently correlated with insulin resistance and islet beta cell function: a study in population with different glucose and lipid metabolism states.

BACKGROUND: Previous studies on the effects of lipotoxicity and oxidative stress on islet beta cell function mainly focused on patients with diabetes, whereas studies on normal glucose tolerance (NGT) are few. The aim of this study was to explore the relationships among triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), oxidative stress indicators, insulin resistance, and beta cell function in populations with different glucose and lipid metabolism states. METHODS: A total of 517 individuals were recruited from a rural community in Beijing, China. Glucose metabolism status was defined according to the results of a 75-g oral glucose tolerance test (OGTT). Dyslipidemia was defined as abnormal TG, HDL-c, or LDL-c levels. The population was divided into four groups: individuals with normal glucose and lipid levels (group A, n = 62); those with dyslipidemia alone (group B, n = 82); those with dysglycemia alone (group C, n = 121); and those with dysglycemia and dyslipidemia (group D, n = 247). Oxidative stress indicators, including superoxide dismutase (SOD), glutathione reductase (GR) and 8-hydroxydeoxyguanosine (8-OHdG), were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI30, DI120) were calculated to assess insulin resistance and islet beta cell function, respectively. Stratified multiple linear regression analysis was used to explore relationships between TG, HDL-c, LDL-c, oxidative stress indicators, and insulin resistance (natural log transformation of HOMA-IR, LnHOMA-IR) and beta cell function (natural log transformation of DI30, Ln DI30). RESULTS: Compared with the control group, populations with dyslipidemia and/or dysglycemia showed significantly increased insulin resistance. Dyslipidemia aggravated insulin resistance and beta cell dysfunction in individuals with dysglycemia. Stratified regression analysis showed that TG positively correlated with LnHOMA-IR in individuals with normal glucose levels (beta = 0.321, 0.327, P = 0.011, 0.003 in groups A and B, respectively) and negatively correlated with LnDI30 in participants with dyslipidemia (beta = - 0.225, - 0.122, P = 0.035, 0.048 in groups B and D, respectively). Reduced serum SOD levels in individuals with dysglycemia plus dyslipidemia were observed, and a negative association between TG and SOD levels was found (r = - 0.461, P < 0.001). CONCLUSION: TG correlated with both insulin resistance and beta cell function in individuals with dyslipidemia alone. SOD negatively correlated with TG, indicating a close relationship between oxidative stress and glucose-lipid metabolism. Due to the adverse effect of hypertriglyceridemia on insulin sensitivity and islet beta cell function, more attention should be paid to the detection and management of hypertriglyceridemia.

Corrigendum to "Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α".

[This corrects the article DOI: 10.1155/2020/7610436.].

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α.

OBJECTIVES: In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL). DESIGNS: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings. Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants. This cross-sectional analysis included 467 participants (34.8% men). Measurements. Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis. RESULTS: There was an inverse relationship between dietary magnesium and LTL (P < 0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α, with an interquarter difference of 3.79 pmol/mL (P for trend = 0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNFα increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31-5.36; P = 0.003) and 1.98 (95% CI: 1.09-3.59; P = 0.008). There was a direct negative effect of dietary magnesium intake on LTL (B = -0.002; P = 0.001), which appeared to be indirectly influenced by TNFα (-0.002 to -0.0005). CONCLUSIONS: Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNFα.

The shape of the glucose response curve during an oral glucose tolerance test heralds ß-cell function in a large Chinese population.

BACKGROUND: The shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict ß-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population. METHODS: A total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. RESULTS: The shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P < 0.001). Individuals in the monophasic group had significantly higher fasting plasma glucose (FPG 5.6 ± 13.5 vs. 5.2 ± 0.6, P < 0.001), fasting insulin (FINS 14.8 ± 8.7 vs. 13.5 ± 7.9, P < 0.01), and homeostasis model assessment of insulin resistance (HOMA-IR 3.8 ± 2.6 vs. 3.1 ± 2.0, P < 0.001) and impaired ß-cell function (disposition index 12.7 ± 14.1 vs. 16.6 ± 17.8, P < 0.001) compared to those in the multiphasic group. CONCLUSION: The monophasic OGTT glucose response curve could reflect impaired ß-cell function in a large Chinese population.