Adipocyte-Derived Exosomal LINC00968 Promotes Mouse Retina Microvascular Endothelial Cell Dysfunction in a High-Glucose Environment by Modulating the miR-361-5p/TRAF3 Axis.

As a major cause of mortality, cardiovascular disease is associated with obesity and diabetes. However, the molecular mechanism by which diabetes-obesity causes cardiovascular complications is largely unknown. In this study, the crosstalk mediated by 3T3-L1 preadipocytes and mouse retina microvascular endothelial cells (mRMECs) was determined after co-culturing performed with a Transwell system or measuring exosome uptake by mRMECs. CCK-8 assays, EdU incorporation assays, TUNEL staining, and ELISAs were used to evaluate the functions of mRMECs. Related protein markers were analyzed by western blotting. Our results showed that LINC00968 levels were significantly elevated in the exosomes derived from H-Glu-induced 3T3-L1 preadipocytes. Both H-Glu treatment and co-culture with 3T3-L1 cells damaged mRMECs, as indicated by lower rates of proliferation and higher rates of apoptosis and cell adhesion molecule expression, as well as by induced inflammation and oxidative stress, which were enhanced by combined H-Glu and co-culture treatment. Furthermore, H-Glu and co-culture treatment increased LINC00968 expression in mRMECs, and the exosomes collected from 3T3-L1 cells had a similar effect. Functionally, LINC00968 inhibition protected mRMECs against the effects of H-Glu and co-culture treatment, while LINC00968 played the opposite role. LINC00968 was found to target miR-361-5p, and TRAF3 was identified as a target gene of miR-361-5p. Finally, miR-361-5p overexpression alleviated the effects of LINC00968 on H-Glu-induced mRMEC dysfunction in vitro. In conclusion, our results indicated that in an H-glu environment, adipocyte exosomes damage microvascular endothelial cells via a LINC00968/miR-361-5p/TRAF3 signaling pathway, which could possibly serve as a target for treating diabetes-obesity-triggered microvascular complications.

Associations between parity, pregnancy loss, and breastfeeding duration and risk of maternal type 2 diabetes: An observational cohort study.

BACKGROUND: Parity, pregnancy loss, and breastfeeding duration were found to be associated with diabetes. However, the results are inconsistent. Also, no epidemiological studies have examined the association of these reproductive factors with diabetes in the same large population. We aim to investigate the associations between parity, pregnancy loss, breastfeeding duration, and the risk of maternal diabetes in middle-aged and elderly Chinese females. METHODS: We included 131 174 females aged ≥40 years from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Multivariable linear regression and logistic regression were used to assess the association between parity, pregnancy loss, and breastfeeding duration and type 2 diabetes. RESULTS: The number of parities and breastfeeding duration were positively related to fasting plasma glucose, 2-hour postload glucose, glycosylated hemoglobin, and homeostatic model assessment of insulin resistance. Compared with those with one birth, nulliparous women or women with 2 or ≥3 births had a significantly increased risk of diabetes. The odds ratios (OR) and 95% confidence intervals (CI) were 1.27 (1.10-1.48), 1.17 (1.12-1.22), and 1.28 (1.21-1.35), respectively. Compared with women without pregnancy loss, those who underwent 2 (OR 1.09; 95% CI, 1.04-1.14) or ≥3 pregnancy losses (OR 1.11; 95% CI, 1.04-1.18) had an increased risk of diabetes. Moreover, women with a breastfeeding duration ≥0 to 6 months (OR 0.82; 95% CI, 0.75-0.90) and ≥6 to 12 months (OR 0.94; 95% CI, 0.89-0.99) had a significantly lower risk of diabetes. CONCLUSIONS: Nulliparous women or women with multiparity or more than one pregnancy loss have an increased risk of diabetes in later life, while women who breastfeed more than 0 to 12 months have a lower risk of diabetes.

Efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease: A protocol of randomized controlled trial.

BACKGROUND: Coronary heart disease is a serious cardiovascular disease. There is coronary atherosclerosis, resulting in lumen stenosis, blockage, and then the symptoms of insufficient blood supply and hypoxia in the myocardium. Chronic heart failure is a kind of syndrome with abnormal ventricular filling and ejection function, which is the final stage of the development of coronary heart disease. At present, the treatment plan of Western medicine can significantly reduce the hospitalization rate, but it is still not satisfactory for the prognosis and mortality of patients. Shenfu injection has advantages in the treatment of heart failure in patients with coronary heart disease, but there is a lack of standard clinical studies to verify it, so the purpose of this randomized controlled study is to evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The patients will be randomly divided into a treatment group and the control group according to 1:1, in which the treatment group is treated with Shenfu injection combined with sodium nitroprusside, and the control group is treated with sodium nitroprusside alone. Both groups will be treated with standard treatment for 7 days and followed up for 30 days to pay attention to their efficacy and safety indexes. The observation indexes include TCM syndrome score, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction, brain natriuretic peptide, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, stroke volume, adverse reactions and so on. We will use SPSS 25.0 software for data analysis. DISCUSSION: This study will evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The results of this experiment will provide a clinical basis for Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in coronary heart disease. TRIAL REGISTRATION: DOI 10.17605/OSF.IO/4KNG3.

Factors Related to Bone Metabolism in Kidney Transplant Recipients.

This study is aimed at establishing the prevalence of osteoporosis and osteopenia in kidney transplant recipients (KTRs) and determining the risk factors for bone mass loss. We invited KTRs who were under regular follow-up at Jiangxi Provincial People's Hospital Affiliated with Nanchang University to attend an assessment of osteoporotic risk assessed by questionnaire, biochemical profile, and dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total hip, and femoral neck. Binary logistic regression models were used to investigate the relationship between the different variables and bone mass density (BMD). A total of 216 patients satisfied the inclusion criteria. The group consisted of 156 men (72.22%) and 60 women (27.78%), and the mean age was 41.50 ± 9.98 years. There were 81 patients with normal bone mass (37.50%) and 135 patients with bone mass loss (62.50%). Logistic regression analysis showed that a higher phosphorus value and higher alkaline phosphatase concentration and a longer use of glucocorticoids were risk factors for bone mass loss in KTRs, and maintaining an appropriate weight and exercising an appropriate number of times per week helped to maintain bone mass.

Exendin-4 promotes bone formation in diabetic states via HDAC1-Wnt/ß-catenin axis.

Exendin-4 has been found to have hypoglycemic effect and prevent bone loss in diabetic patients, but its mechanism of preventing bone loss is still unclear. In this study, high-fat diet combined with streptozotocin was used to establish type 2 diabetes mellitus (T2DM) mice, and bone marrow mesenchyme stem cells (BMSCs) were isolated for osteogenic induction in vitro. Alizarin red staining and ALP activity detection were used to observe the effect of exendin-4 on osteogenic differentiation of BMSCs. Western blot was used to detect the proteins expression in BMSCs. In vivo, the effects of exendin-4 treatment on body weight, blood glucose, bone density and bone quality of T2DM mice were observed by treatment with exendin-4. The results showed that exendin-4 promoted osteogenic differentiation of T2DM derived BMSCs, down-regulated histone deacetylase 1 (HDAC1) and p-ß-Catenin proteins expression, and up-regulated Wnt3, ß-Catenin and runt-related transcription factor 2 (Runx 2) proteins expression. In vivo, exendin-4 effectively suppressed the blood glucose and increased body weight of T2DM mice, and significantly improved bone density and bone quality of the right tibia. Interestingly, by over-expression of HDAC1 in BMSCs, the effect of exendin-4 on promoting osteogenic differentiation of BMSCs was attenuated, and the regulation of Wnt3a, ß-Catenin, p-ß-Catenin or Runx2 proteins were reversed. By injecting adenovirus containing HDAC1 into the right tibia of mice, the effect of exendin-4 on bone density and bone quality of T2DM mice was significantly attenuated. All above results suggest that the HDAC1-Wnt/ß-Catenin signal axis is involved in the anti-diabetic bone loss effect of exendin-4, and HDAC1 may be the target of exendin-4.

Clinical Treatment Efficacy of Total Thyroidectomy Combined with Radioactive Iodine on Treatment of Thyroid Cancer and Its Effect on the Quality of Life of Patients.

BACKGROUND: To investigate the treatment efficacy of radioactive iodine therapy on patients after total thyroidectomy and its effect on the quality of life. METHODS: A retrospective analysis of clinical data of 120 thyroid cancer patients admitted to Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China from February 2014 to February 2017 was performed. According to different treatment methods, they were divided into observation group of 62 cases and control group of 58 cases. Both groups were treated with total thyroidectomy. The control group was treated with anti-infection and prevention of complications after operation, the observation group with radioactive iodine therapy. Treatment efficacy, quality of life score, recurrent laryngeal nerve injury and postoperative survival rate were compared between the two groups. RESULTS: The total effective rate of treatment in the test group was 98.39%, significantly higher than 72.41% in the control group, with a statistically significant difference (P<0.05). Compared with the control group, the fatigue score of the test group was lower, but the score in the area of emotion function and the overall health status score were higher, with a statistically significant difference (P<0.05). There was no significant difference in the recurrent laryngeal nerve injury between the two groups of patients. The postoperative survival rate of the test group of patients was 96.77%, significantly higher than 86.21% of the control group. CONCLUSION: The effect of radioactive iodine therapy after total thyroidectomy is remarkable, which can significantly improve the clinical treatment efficacy and postoperative quality of life of patients, worthy of clinical application.