Association of Monocyte-to-HDL Cholesterol Ratio with Endothelial Dysfunction in Patients with Type 2 Diabetes.

Aims: To explore the relationship between monocyte-to-HDL cholesterol ratio (MHR) and endothelial function in patients with type 2 diabetes (T2DM). Methods: 243 patients diagnosed with T2DM were enrolled in this cross-sectional study. Patients were divided into two groups by flow-mediated dilation (FMD) quintile as nonendothelial dysfunction (FMD ≥ 6.4%) and endothelial dysfunction (FMD < 6.4%). The relationship between MHR and FMD was analyzed using Spearman's correlation, partial correlation, and multiple logistic regression analysis. ROC curve was fitted to evaluate the ability of MHR to predict endothelial dysfunction. Results: Endothelial dysfunction was present in 193 (79%) patients. Patients with endothelial dysfunction had higher MHR (p < 0.05) than those without endothelial dysfunction. Furthermore, MHR had a significantly positive correlation with endothelial dysfunction (r = 0.17, p < 0.05), and the positive association persisted even after controlling for confounding factors (r = 0.14, p < 0.05). Logistic regression showed that MHR was an independent contributor for endothelial dysfunction (OR: 1.35 (1.08, 1.70), p < 0.05) and the risk of endothelial dysfunction increases by 61% with each standard deviation increase in MHR (OR: 1.61 (1.12, 2.30), p < 0.05) (model 1). After adjusting for sex, age, BMI, disease course, hypertension, smoking, and drinking (model 2) as well as HbA1c, HOMA-IR, C-reactive protein, and TG (model 3), similar results were obtained. In ROC analysis, the area of under the ROC curve (AUC) for MHR was 0.60 (95% CI 0.52-0.69, p < 0.05). Conclusion: MHR was independently associated with endothelial dysfunction in T2DM patients. It could be a new biomarker for vascular endothelial function assessment.

Correlation Between Abdominal Fat Distribution and Serum Uric Acid in Patients Recently Diagnosed with Type 2 Diabetes.

Objective: To investigated the link between the distribution of abdominal fat and the concentration of serum uric acid (SUA) in individuals recently diagnosed with type 2 diabetes. Methods: Studied 364 individuals had been diagnosed with type 2 diabetes within one month, and evaluated factors such as the distribution of fat in the abdomen, indicators related to glucose and lipid metabolism. The participants' SUA concentrations were divided into a normal control group (CG) and a hyperuricemia group (HG). Results: The HG group had elevated abdominal subcutaneous fat area (SFA), visceral fat content (VFA), body mass index (BMI), fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG), glycosylated albumin (GA), serum creatinine (SCr), triacylglycerol (TG), and lower values in glomerular filtration rate (eGFR), high-density lipoprotein cholesterol (HDL-C) when compared to the CG group (P < 0.05). Among the obese individuals, the hyperuricemia subgroup exhibited higher measurements in waistline, hipline, VFA, SFA, BMI, PBG, SCr, TG, and lower HDL-C (P < 0.05) compared to the subgroup with normal uric acid levels. In the non-obese group, the hyperuricemia subgroup showed higher VFA, SCr, and FBG levels, and lower HDL-C (P < 0.05). There was a positive correlation between VFA and serum uric acid (SUA) levels (r = 0.329, P < 0.0001). Logistic regression analysis indicated a 24% increased risk of hyperuricemia with every 10cm2 increase in abdominal VFA. Generate the Receiver Operating Characteristic (ROC) curve analysis revealed that VFA was the most effective predictor of hyperuricemia and insulin resistance (P < 0.05). Conclusion: Newly diagnosed type 2 diabetes patients exhibit a strong correlation between abdominal visceral fat and SUA concentration, the former is identified as an autonomous risk factor for hyperuricemia and an effective indicator for assessing the presence of hyperuricemia and predicting insulin resistance.

Efficacy and Safety of Wuling Powder in the Treatment of Patients with Diabetic Nephropathy: A Systematic Review and Meta-Analysis.

Background: Wuling powder is a classical formula of traditional Chinese medicine (TCM), which is extensively applied to treat diabetic nephropathy (DN). However, there are no related reports on systematically evaluating the efficacy of Wuling powder in the treatment of DN. Targeted at this, this study was developed. Materials and Methods: This study systematically searched related articles from nine databases, including PubMed, Cochrane Library, Embase, Web of Science, China Knowledge Infrastructure (CNKI), China Biomedical CD-ROM (Sino Med), Wanfang database, Vipers database (VIP), and the China Clinical Trials Registry website. The randomized controlled trials (RCTs) involving Wuling Power to treat DN were included, which were published from the established data of the above databases to March 2022. In addition, the language of the studies was not restricted. Studies were meta-analyzed using the RevMan 5.4 software given in the Cochrane Collaboration Network. The treatment efficacy was measured using the weighted mean differences (WMD) and 95% confidence intervals (CI). Results: 24 studies were included for the final analysis. 24 h urine volume (WMD = 357.95; 95% CI [322.83, 393.06], p < 0.00001), 24 h urine protein quantification(24 h UPQ) (WMD = -1.30; 95% CI [-1.82, -0.78], p < 0.00001), serum creatinine (Scr) (WMD = -10.17; 95% CI [-11.13, -9.21], p < 0.00001), blood urea nitrogen (BUN) (WMD = -1.62; 95% CI [-2.30, -0.93], p < 0.00001), urinary albumin excretion rate (UAER) (WMD = -24.73; 95% CI [-35.46, -13.99], p < 0.00001), fasting blood glucose (FBG) (WMD = -0.63.95% CI [-0.97, -0.30], p = 0.002), glycated hemoglobin (WMD = -0.11; 95% CI [-0.30, 0.08], p=0.26), total cholesterol (TC) (WMD = -0.63; 95% CI [-1.23, -0.04], p=0.04), triglycerides (TG) (WMD = -0.46. 95% CI [-0.70, -0.23], p=0.0001), high-density lipoprotein cholesterol (HDL-C) (WMD = -0.32; 95% CI [0.03, 0.62], p=0.03), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.57; 95% CI [-0.77, -0.37], p < 0.00001), and total effective rate (TER) (response ratio (RR) = 1.40; 95% CI [1.32, 1.48]; p < 0.00001) were concluded. The Wuling powder in the treatment of DN was statistically significant in all the above outcome indicators, and the efficacy of the treatment group was better than that of the control group. Conclusion: The results of this study provided evidence for the clinical application of Wuling powder to treat the DN, but it had to be further validated in higher-quality clinical studies.

MicroRNA-1323 downregulation promotes migration and invasion of breast cancer cells by targeting tumour protein D52.

Breast cancer (BC) is one of the most common malignancies globally in women, with high mortality rate as a result of tumour metastasis. MicroRNAs play vital roles in the occurrence and development of human cancer. This study aimed to investigate the biological roles of miR-1323 in BC. The expression levels of miR-1323 were detected by quantitative real-time PCR assay. The effect of miR-1323 on BC cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Wound healing analysis and Matrigel Transwell assay were conducted to evaluate miR-1323-mediated BC cell migration and invasion. A luciferase reporter assay was used to test the target of miR-1323. We found that miR-1323 levels were downregulated in BC tissues and serums. Low-miR-1323 levels were associated with lymph node metastasis and advanced clinical stage. Tumour protein D52 (TPD52) was identified as a direct target of miR-1323. Low expression of miR-1323 contributed to the overexpression of TPD52 leading to enhanced BC progression. Our findings suggest that silencing of miR-1323 enhances BC development by regulating TPD52 expression, suggesting that miR-1323 and TPD52 may serve as potential therapeutic targets for BC treatment.

Combining the LKB NTCP model with radiosensitivity parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.

The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/ß, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/ß or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.

Effect of different cell cluster models on the radiobiological output for (211)At-radioimmunotherapy.

The cell cluster modeling is a widely used method to estimate the small-scale dosimetry and provides the implication for a clinic. This work evaluated the effect of different regular cluster models on the radiobiological outputs for (211)At-radioimmunotherapy. The cell activity threshold was estimated using a tumor control probability of 0.90. Basically, regular models show similar features with cluster configuration and cell dimension variation. However, their individual results such as the cumulated activity threshold per cell and the prescription dose per volume should not be substituted reciprocally. The tissue composed of smaller cells or midcell packing will need a little more high prescription dose per volume. The radiation sensitivity parameters in a linear-quadratic model are critical to decide the radiobiological response with dose. The cumulated cell activity threshold increases exponentially with α decreasing, and its influence on the big cell dimension is more than on the small one. The different subsources affect radioresistant organs or tissues more remarkably than radiosensitive ones, especially the cells with large cytoplasm. The heterogeneous activity of Gaussian distribution will decrease the therapeutical effectiveness for the nucleus source, but its influence on the cytoplasm and cell surface sources is a little uncertain, as their real mean value is always higher than its set mean value by assuming the cell activity uptakes from zero. Careful usage of underdose with heterogeneous activity distribution should be practiced in clinics. The deteriorated heterogeneous distribution will salvage the potential subversive and lead to the failure of tumor local control. Some cells with no or little activity that are located on the edge or vertex of cube or corner models will have the ability to survive, as there is a lack of a part of the cross-fire dose effect, and so more attention should be paid in selecting the dosage. Although this work focuses on the clinic implication of (211)At in α-radioimmunotherapy, these cell cluster models can be generalized to other radionuclides.