Serum osteocalcin is inversely associated with lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus.

Serum osteocalcin (OCN) is closely related to metabolic risk factors, and the relationship between OCN and atherosclerosis has been investigated. However, it is still controversial. Herein, we explored the potential correlation between serum total OCN and lower extremity atherosclerotic disease (LEAD) in 326 hospitalized Chinese patients with type 2 diabetes mellitus (T2DM). Femoral intima-media thickness (F-IMT) and lower limb atherosclerotic plaque were assessed through color Doppler ultrasound. Subjects with LEAD had significantly lower serum OCN levels compared with those without LEAD (14.54 [14.10-14.89] ng/mL versus 16.79 [15.86-18.04] ng/mL, p < 0.001). Spearman's correlation analysis revealed that serum OCN levels were positively associated with high density lipoprotein cholesterol (HDL-C) and negatively associated with fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), hemoglobin A1c (HbA1c), waist-to-hip ratio (WHR) and F-IMT. Multiple logistic analysis revealed that OCN (OR 0.938, 95% confidence interval (CI 0.933-0.950, p = 0.003) and glomerular filtration rate (GFR) (OR 0.990, 95% CI 0.985-0.996, p = 0.003) were independently and inversely associated with LEAD, while age (OR 1.140, 95% CI 1.127-1.148, p < 0.001), diabetes duration (OR 1.068, 95% CI 1.039-1.080, p < 0.005) and uric acid (UA) (OR 1.005, 95% CI 1.002-1.007, p = 0.032) were independently and positively associated with LEAD. Additionally, multiple linear regression analysis revealed that serum OCN levels were negatively associated with F-IMT (standardized ß = -0.180, p = 0.002). In Chinese patients with T2DM, serum OCN levels were independently and inversely correlated with LEAD.

Increased ß-site APP cleaving enzyme 1-mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive impairment.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are at a high risk of cognitive impairment, with insulin resistance playing a pivotal role. ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance and the risk of cognitive impairment in T2DM remain unclear. METHODS: We measured plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid precursor protein (APPsw) and insulin receptor ß subunit (INSR-ß), and soluble INSR (sINSR) levels in a clinical cohort study. RESULTS: T2DM patients with or without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 enzymatic activities for APPsw and INSR-ß, and sINSR levels. Moreover, the glycemic status correlated with elevated BACE1 levels and BACE1-mediated INSR cleavage, which was associated with insulin resistance. DISCUSSION: The elevated BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk through both amyloidogenesis and insulin resistance.

CREB-upregulated lncRNA MEG3 promotes hepatic gluconeogenesis by regulating miR-302a-3p-CRTC2 axis.

Hepatic gluconeogenesis is the major contributor to hyperglycemia in diabetes. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to promote hepatic insulin resistance; however, the underlying mechanism involving hepatic gluconeogenesis remains unclear. This study aims to investigate the potential role of MEG3 in hepatic gluconeogenesis. Mouse primary hepatocytes were used in this study. Cell transfection was performed for the overexpression or knockdown of specific genes. Expressions of MEG3, miR-302a-3p, CREB-regulated transcriptional coactivator 2 (CRTC2), protein kinase A (PKA), cAMP-response element binding protein (CREB), PPARγ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pc) were determined by quantitative real-time polymerase chain reaction (qRT-qPCR) and Western blot analysis, respectively. The association among MEG3, miR-302a-3p, and CRTC2 was disclosed by dual-luciferase reporter assay. MEG3 was highly expressed in high glucagon-treated mouse primary hepatocytes. CREB-induced MEG3 upregulation increased gluconeogenic gene expression in high glucagon-treated primary hepatocytes, while MEG3 interference led to an opposite effect. MEG3 served as a competing endogenous RNA (ceRNA) to upregulate CRTC2 by targeting miR-302a-3p in primary hepatocytes, thereby increasing PGC-1α-PEPCK/G6Pc. CREB-upregulated MEG3-enhanced hepatic gluconeogenesis via mediating miR-302a-3p-CRTC2 axis, revealing that MEG3 might be a potential target and therapeutic strategy for diabetes.

Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression.

BACKGROUND: Hepatic insulin resistance is a major characteristic of type 2 diabetes mellitus. LncRNA MEG3 has been shown to correlate to hepatic glucose production; however, the underlying mechanism remains unclear. This study aims to investigate the role of MEG3 in hepatic insulin resistance. METHODS: High-fat diet mice, ob/ob mice and mice primary hepatocytes were used in this study. Expression of MEG3, FoxO1, G6pc and Pepck were determined by real-time PCR. FoxO1, G6pc, Pepck, HDAC1 and HDAC3 protein levels were analyzed by western blotting. Hepatic gluconeogenesis, glycogen accumulation, triglyceride and glycogen contents were measured by corresponding assay or kit, and body weight was monitored after an overnight fast. RESULTS: Gene expression of MEG3 was upregulated in high-fat diet and ob/ob mice and increased by palmitate, oleate or linoleate. MEG3 overexpression significantly increased FoxO1, G6pc, Pepck mRNA expressions and hepatic gluconeogenesis and suppressed insulin-stimulated glycogen synthesis in primary hepatocytes, whereas palmitate-induced increase of FoxO1, G6pc and Pepck protein expressions could be reversed by MEG3 interference. In addition, high fat enhanced expression of lncRNA MEG3 in hepatocytes through histone acetylation. Furthermore, MEG3 interference could reverse the up-regulation of triglyceride as well as impaired glucose tolerance and down-regulation of glucogen content in high-fat diet mice or ob/ob mice. CONCLUSION: Upregulation of lncRNA MEG3 enhances hepatic insulin resistance via increasing foxO1expression, suggesting that MEG3 may be a potential target and therapeutic strategy for diabetes.

Population dynamics of migrant wheat aphids in China's main wheat production region and their interactions with bacterial symbionts.

Sitobion miscanthi, Rhopalosiphum padi, and Schizaphis graminum are the three main pests in Chinese wheat-producing regions. In 2020, they are classified into the Chinese Class I list of agricultural diseases and pests, due to their severe harm to wheat plantings. S. miscanthi, R. padi, and S. graminum are migrant pests, and understanding their migration patterns and simulating their migration trajectories would improve forecasting and controlling them. Furthermore, the bacterial community of the migrant wheat aphid is also less known. In this study, we employed a suction trap to uncover the migration patterns of the three wheat aphid species in Yuanyang county, Henan province, during 2018 to 2020. And then the migration trajectories of S. miscanthi and R. padi were simulated using the NOAA HYSPLIT model. The interactions between wheat aphids and bacteria were further revealed by specific PCR and 16S rRNA amplicon sequencing. The results showed that the population dynamics of migrant wheat aphids was varied. Most of the trapped samples were identified to be R. padi, and S. graminum was the least collected sample. Typically, R. padi had two migration peaks in the 3 years, whereas S. miscanthi and S. graminum only exhibited one migration peak in 2018 and 2019. Moreover, the aphid migration trajectories varied over the years. Generally, the aphids originated from the south and migrated to the north. Herein, the infections of three main aphid facultative bacterial symbionts, Serratia symbiotica, Hamiltonella defensa, and Regiella insercticola, were detected in S. miscanthi and R. padi with specific PCR. Rickettsiella, Arsenophonus, Rickettsia, and Wolbachia were further identified with 16S rRNA amplicon sequencing. Biomarker searching indicated that Arsenophonus was significantly enriched in R. padi. Furthermore, diversity analyses showed that the bacterial community of R. padi had a higher richness and evenness than that of S. miscanthi. In conclusion, this study expands our knowledge about the migration patterns of aphids in the main wheat plant region of China and reveals the interactions between bacterial symbionts and migrant aphids.

Different Complement Activation Pathways Underly Cognitive Impairment and Type 2 Diabetes Mellitus Combined With Cognitive Impairment.

Background: The immune response and the complement system are associated with cognitive impairment and diabetes mellitus, respectively. Activation of the complement system in these diseases occurs mainly through either the classical pathway or the alternative pathway. However, the specific complement proteins involved in the development of the type 2 diabetes mellitus (T2DM) and cognitive impairment are still unclear. Here, we investigated complement proteins in serum from patients with T2DM, cognitive impairment, or both T2DM and cognitive impairment. Objective: To investigate the levels of serum immune complement proteins in patients with T2DM, cognitive impairment, or T2DM combined with cognitive impairment and the associations between these complement proteins and risk factors for T2DM or cognitive impairment. Methods: Clinical markers were collected from blood samples of 264 participants. Luminex multiplex assays were used to detect serum complement proteins. All statistical analyses were performed using Prism or R studio. Results: There was a difference in serum levels of the complement proteins C1q, C3, C3b, and FH between the three different groups. Hyperglycemia was significantly correlated with elevated C3b or reduced C3, C1q, and FH. In addition, hyperlipidemia was positively correlated with elevated levels of C3, C4, C1q, and FH proteins. There was an association between C1q, C3, C4, and FH and ß-pancreas cell function, whereas only FH was associated with insulin resistance. Higher serum C1q was significantly associated with an increased risk of cognitive impairment. Conclusion: Serum levels of complement proteins were closely associated with hyperglycemia and hyperlipidemia. We found that classical complement pathway activation mainly occurred in the cognitive impairment only group, whereas the alternative pathway may reflect T2DM and T2DM with cognitive impairment.

Hyperoside attenuates non-alcoholic fatty liver disease through targeting Nr4A1 in macrophages.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. To date, no medications for NAFLD have been approved by relevant governmental agencies. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NAFLD. Hyperoside, a flavonoid compound mainly found in medicinal plants, has many biological effects, but the role of hyperoside in the physiological process of NAFLD is poorly defined. This study demonstrated that hyperoside exerts protective effects against high-fat diet (HFD)-induced NAFLD and regulates macrophage polarization in an Nr4A1-dependent manner. After 16 weeks on a HFD, hepatic steatosis, insulin resistance, and inflammatory responses were significantly ameliorated in hyperoside-treated HFD-fed wild-type mice, and hyperoside facilitated the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 subtype. Nr4A1 was found to be upregulated in hyperoside-treated HFD-fed mice, and hyperoside did not improve HFD-induced NAFLD or regulate macrophage polarization in Nr4A1-deficient mice. In conclusion, hyperoside may have therapeutic potential in preventing the pathological progression of NAFLD.

Clinical expert consensus on standard care of blood glucose for residents in senior care facility in China (2021 edition).

With the demographic changes, more and more elderly people have chosen to spend their retirement life in a senior care facility. The elderly people in senior care facility are commonly suffering from various geriatric syndromes, including declined daily living activities, cognitive dysfunction, frailty, comorbidities, and polypharmacy, which make them vulnerable to adverse effects, like hypoglycemia and fall. Therefore, layered management is necessary for this population with group disparities. However, the staff in senior care facility vary greatly in concepts and skills on management of senile diabetic population, which needs urgently to be standardized and improved. For this purpose, based on literature review and panel discussion, 28 recommendations are proposed in respect of the standardized management of blood glucose, covering the comprehensive assessment, layered management and grouping, exercise, nutrition, glucose monitoring, identification and treatment of severe hyperglycemia, identification of macrovascular and microvascular complications, management of hypoglycemic drugs, falls and choking and other common problems, blood glucose screening, hypoglycemia prevention, and blood glucose management in major public health events or serious natural disasters. This guideline aims to standardize management skills of medical staff and caregivers in senior care facility for the blood glucose of elderly people and improve their quality of life.

A New Neurovascular Panel Discriminates Between Patients with Type 2 Diabetes Mellitus with Cognitive Impairment and Cognitive Impairment Alone.

BACKGROUND: Recent studies showed that type 2 diabetes mellitus (T2DM) may increase the risk of cognitive impairment, but there are few biomarkers to diagnostically discriminate T2DM-associated cognitive impairment and cognitive impairment alone. In this study, we assessed certain cytokines involved in inflammation and vascular diseases and identified special panel of cytokines that could differentiate between T2DM and cognitive impairment. OBJECTIVE: To investigate associations and differences between T2DM and cognitive impairment by cytokines analysis. METHODS: A total of 264 participants were recruited, their blood samples were collected, and plasma and serum were separated and stored at - 80°C until the assessment of amyloid-ß (Aß)42, Aß40 and 8 kinds of cytokines by Luminex multiplex assays. RESULTS: Plasma Aß40 is higher whereas Aß42/40 ratio is lower in cognitive impairment and T2DM-associated cognitive impairment compared to other groups. As compared to health control, YKL-40 level was upregulated in cognitive impairment, PRGN was downregulated in T2DM associated cognitive impairment, OPN was substantially decreased in T2DM, and IL-6 was elevated in cognitive impairment and T2DM-associated cognitive impairment. Interestingly, VEGF and S100B were induced in T2DM when compared with cognitive impairment, and NSE level in T2DM-associated cognitive impairment is significantly lower than in T2DM or cognitive impairment. CONCLUSION: Aß42, Aß40, and Aß42/40 ratio cannot distinguish T2DM-associated cognitive impairment from cognitive impairment. Certain cytokines (YKL-40, NSE, and VEGF) have good performance in distinguishing T2DM-associated cognitive impairment from simple cognitive impairment. Taken together, this may improve the accuracy of the diagnosis and establishment of individualized therapy.

Serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies.

OBJECTIVE: This study was designed to investigate serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies (TPOAbs). METHODS: We screened 1607 euthyroid subjects aged 35-65 years old. All the subjects were divided into 2 groups (i.e., TPOAb-positive group, n=205; TPOAb-negative group, n=1402) according to the level of TPOAb. The subjects were then subgrouped according to serum thyroid stimulating hormone (TSH) levels; those with a TSH level of 0.3-0.99 mIU/L, 1.0-1.89 mIU/L, and 1.9-4.80 mIU/L were classified into the low-normal, mid-range, and high-normal TSH subgroups, respectively). Each TSH group further subdivided into TPOAb-positive and TPOAb-negative subgroup. Data regarding the subjects' height, body weight, blood pressure, and levels of serum TSH, TPOAb, fasting plasma glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were collected. RESULTS: Compared with TPOAb-negative subjects, TPOAb-positive patients had higher levels of TSH, TC, and HDL-C (P=0.001, P=0.012, and P=0.049 respectively) with a tendency for increased LDL-C levels (P=0.053). In the low-normal TSH subgroup, subjects with and without TPOAb had similar levels of TSH, TC, HDL-C, and LDL-C (P>0.05). In mid-range TSH subgroup, TPOAb-positive patients had higher HDL-C levels compared to TPOAb-negative subjects (P=0.008) and a tendency for increased TC levels (P=0.121). In the high-normal TSH subgroup, TPOAb-positive patients had higher TSH and TC levels compared to TPOAb-negative subjects (P<0.001 and P=0.046 respectively). CONCLUSIONS: High TPOAb levels above the normal range appears in euthyroid population, dyslipidemia have begun.

Comparison between cisplatin plus vinorelbine and cisplatin plus docetaxel in the treatment of advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials.

Whether cisplatin plus vinorelbine (VC) or cisplatin plus docetaxel (DC) are equally effective in the treatment of advanced non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to compare the VC and DC regimens in the first-line treatment of advanced NSCLC. A search was conducted through PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the Chinese Biomedical Literature database (CBM). The language of the publication was not considered to be a limitation. The recruited trials were evaluated for eligibility and quality and the data were extracted and analyzed. The endpoints were overall response, survival rate and toxicity. We analyzed 9 randomized controlled trials (RCTs), including a total of 1,886 patients. Patients receiving DC therapy exhibited a significantly higher response rate [relative risk (RR)=0.83, 95% CI: 0.73-0.95 and P=0.007] and 2-year survival rate (RR=0.65, 95% CI: 0.50-0.84 and P=0.001). However, the 1-year survival rate for the two cisplatin-based regimens were comparable (RR=0.90, 95% CI: 0.81-1.01 and P=0.07). Patients receiving the VC regimen more frequently developed grade 3/4 leucopenia, anemia and vomiting, whereas those receiving DC chemotherapy were more prone to grade 3/4 diarrhea. The incidence of grade 3/4 neutropenia, thrombocytopenia and nausea were similar between the two arms. In conclusion, our study indicated that DC is superior to the VC regimen in terms of tumor response rate, 2-year survival rate and safety for the first-line treatment of advanced NSCLC.

[Effects of different education methods on compliance and satisfaction of the patients with temporomandibular disorders].

OBJECTIVE: To compare the effects of video or leaflet in conjunction with traditional patient education (TPE) with traditional patient education alone for the compliance and satisfaction of the patients with temporomandibular disorders (TMD). METHODS: One hundred and thirty-three patients with TMD who needed intra-articular injection of hyaluronate were included and randomly divided into three groups: Group I accepted video education plus TPE, Group II accepted leaflet education plus TPE, Group III accepted TPE alone. All the participants were recorded by demographic characteristics (sex, age) before treatment, and their compliance, satisfaction and self-exercise were also recorded after one month followed-up. RESULTS: The baseline parameters (sex, age and diagnosis) of the groups were similar (P > 0.05). Seventeen participants lost in follow-up, including 4.5% in Group I, 11.1% in Group II and 22.7% in Group III. There were significant differences in lost rates among the three groups (P = 0.035). The rates of participants who exactly followed the appointed follow-up were higher in Group I and II than in group III (P = 0.04). And the satisfaction rates were 90.5% in Group I, 92.5% in Group II, 76.5% in Group III. The satisfaction rates of Group I and Group II were significantly higher than that of Group III (P = 0.05). The patients in Group I and Group II were more compliant with the self-exercise than that in Group III (P = 0.007). CONCLUSION: Adding video or leaflet education to the TPE could increase the patients' compliance, satisfaction and execution of the self-exercise.

Relevance of plasma obestatin and early arteriosclerosis in patients with type 2 diabetes mellitus.

We investigated the correlation between obestatin and metabolic parameters and carotid intima-media thickness (IMT) in plasma of patients with type 2 diabetes mellitus (T2DM). We collected 103 patients aged from 60 to 83 years (69.26 ± 5.83 years) form January, 2007 to May, 2009. All patients were divided into normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM according to the oral glucose tolerance test (OGTT). We found that higher levels of fasting insulin (Fins), fasting blood glucose, 2 h OGTT glucose, homeostasis model assessment of insulin resistance (HOMA-IR), low density lipoprotein cholesterol, glycated haemoglobin, and C-reactive protein (CRP), as well as lower obestatin level and higher intima-media thickness level (IMT), existed in T2DM group compared with NGT group and IGT group (P < 0.01). Also, obestatin level was independently associated with HOMA-IR and CRP, while IMT level was independently associated with HOMA-IR, triglyceride, Fins, and obestatin (P < 0.01), based on stepwise multiple regression analysis. Therefore, we deduced that the low level of plasma obestatin might be related to early arteriosclerosis in patients with T2DM via increasing IMT level, and elevated plasma obestatin levels might protect T2DM patients against carotid atherosclerosis to some extent.