Efficacy of Apagliflozin Plus Pentoxifylline in the Treatment of Early Diabetic Nephropathy and Its Effect on Serum Inflammatory Factors and Immune Function.

Objective: To explore the efficacy of dapagliflozin plus pentoxifylline in the treatment of early diabetic nephropathy and its effect on serum inflammatory factors and immune function. Methods: A total of 90 patients with early diabetic nephropathy who were admitted to Cangzhou Central Hospital from January 2019 to January 2022 were recruited and randomized (1:1) into a control group and an observation group using the random number table method. The control group was treated with dapagliflozin, and the observation group was treated with pentoxifylline plus dapagliflozin. The effectiveness of urinary α (1) microglobulin (α 1-mg) was determined by immunoturbidimetric method, and urinary ß (2) microglobulin (ß 2-mg) was determined. Urine creatinine was determined enzymatically, and the urinary microprotein albumin creatinine ratio (mAlb/Cr) was calculated. The levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] were detected. Before and after treatment, 3 mL of venous blood was drawn from the two groups of patients, and serum CD4+, CD8+, and CD4+/CD8+ levels were detected. The incidence of adverse reactions between the two groups was calculated. Results: Dapagliflozin plus pentoxifylline was associated with a higher effective rate than dapagliflozin alone (96.67% vs 81.67%) (RR 0·80 [95% CI 0·61-0.98]; P = .021). Dapagliflozin plus pentoxifylline led to lower renal function parameters versus dapagliflozin alone, in favor of the observation group (RR 0.67 [95% CI 0.66-0.88]; P = .032). After treatment, the serum levels of IL-6 and TNF-α in patients treated with dapagliflozin plus pentoxifylline were lower than counterparts treated with dapagliflozin (RR 0.62 [95% CI 0.51-0.78]; P = .037). After treatment, CD4+ and CD4+/CD8+ in the two groups were increased compared with baseline parameters, and the level of CD8+ was decreased ; the increase and decrease were greater in the observation group than in the control group (RR 0.70 [95% CI 0.71-0.96]; P = .044) (RR 0.53 [95% CI 0.41-0.78]; P = .033). The two groups demonstrated similar safety profiles with no statistical difference observed in the incidence of adverse reactions between the two groups (RR 0.73 [95% CI 0.73-1.08]; P = .051). Conclusion: Dapagliflozin plus pentoxifylline might be a promising alternative in the treatment of patients with early diabetic nephropathy, it significantly mitigates the body's inflammatory response, enhances immune function, attenuates the main clinical symptoms, with a high safety profile.

Association between sensitivity to thyroid hormone indices and osteoporosis in euthyroid patients with type 2 diabetes mellitus.

Background: Thyroid hormones are known to regulate bone metabolism and may influence bone mineral density (BMD), as well as the risk of osteoporosis (OP) and fractures in patients with type 2 diabetes mellitus (T2DM). Recently, sensitivity to thyroid hormone indices has been linked with T2DM and OP independently. However, the relationship between thyroid hormone sensitivity and OP in euthyroid T2DM patients has yet to be investigated. Objectives: The aim of this study was to determine the association between sensitivity to thyroid hormone indices and the risk of OP in euthyroid patients with T2DM. Design: This study employed a retrospective, cross-sectional design and utilized data acquired from the Cangzhou Central Hospital in China between 2019 and 2020. Methods: We retrospectively analyzed the data of 433 patients with T2DM for anthropometric measurements, clinical laboratory test results, and BMD. The thyroid-stimulating hormone index, thyrotroph thyroxine resistance index, and thyroid feedback quantile-based index (TFQI) were calculated to determine thyroid hormone sensitivity. Finally, multivariable logistic regression, generalized additive models, and subgroup analysis were performed to detect the association between sensitivity to thyroid hormone indices and the risk of OP in these patients. Results: We did not observe a statistically significant linear relationship between sensitivity to thyroid hormones indices and OP after covariate adjustment. However, a nonlinear relationship existed between TFQI and the prevalence of OP. The inflection point of the TFQI was at -0.29. The effect sizes (odds ratio) on the left and right of the inflection point were 0.07 [95% confidence interval (CI): 0.01-0.71; p = 0.024] and 2.78 (95% CI: 1.02-7.58; p = 0.046), respectively. This trend was consistent in older female patients with higher body mass index (BMI; 25-30 kg/m2). Conclusion: An approximate U-shaped relationship was observed between sensitivity to thyroid hormone indices and OP risk in euthyroid patients with T2DM with variations in sex, age, and BMI. These findings provide a new perspective to elucidate the role of thyroid hormones in OP, specifically in patients with T2DM.

Development of Machine Learning Models for Predicting Osteoporosis in Patients with Type 2 Diabetes Mellitus-A Preliminary Study.

Purpose: Diagnosing osteoporosis in T2DM based on bone mineral density (BMD) remains challenging. We sought to develop prediction models employing machine learning algorithms for use as screening instruments for osteoporosis in T2DM patients. Patients and Methods: Data were collected from 433 participants and analyzed using nine categorical machine learning algorithms to select features based on demographic and clinical variables. Multiple classification models were compared using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, sensitivity, specificity, the average precision (AP), precision, F1 score, precision-recall curves, calibration plots, and decision curve analysis (DCA) to determine the best model. In addition, 5-fold cross-validation was utilized to optimize the model, followed by an evaluation of feature significance using Shapley Additive exPlanations (SHAP). Using latent class analysis (LCA), distinct subpopulations were identified by constructing several discrete clusters. Results: In this study, nine feature variables were identified to construct predictive models for osteoporosis in individuals with T2DM. The machine learning algorithms achieved an AP range of 0.444-1.000. The XGBoost model was selected as the final prediction model with an AUROC of 0.940 in the training set, 0.772 in the validation set for 5-fold cross-validation, and 0.872 in the test set. Using SHAP methodology, 25(OH)D was identified as the most important risk factor. Additionally, a 3-Class model was constructed using LCA, which categorized individuals into high, medium, and low-risk groups. Conclusion: Our study developed a predictive model with high accuracy and clinical validity for predicting osteoporosis in type 2 diabetes patients. We also identified three subpopulations with varying osteoporosis risk using clustering. However, limited sample size warrants cautious interpretation of results, and validation in larger cohorts is needed.

Chemerin/CMKLR1 Axis Promotes the Progression of Proliferative Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes, and the levels of chemerin were associated with the severity of DR. However, there is no research on chemerin in the development of proliferative diabetic retinopathy (PDR). Therefore, our study aimed to explore the relationship between chemerin and PDR. METHODS: The levels of chemerin/chemokine-like receptor (CMKLR1), proinflammatory cytokines, and vascular endothelial growth factor (VEGF) in 90 cases of PDR and nonproliferative diabetic retinopathy (NPDR) patients and in high glucose (HG) stimulated human retinal pigment epithelium cells (ARPE-19) were evaluated by ELISA. Moreover, chemerin was added into HG-induced ARPE-19 cells to assess its effect on proinflammatory cytokines and VEGF. RESULTS: The levels of chemerin/CMKLR1 were higher in PDR patients than NPDR ones, and chemerin was positively correlated with CMKLR1 in PDR patients. Compared to NPDR, the secretions of proinflammatory cytokines and VEGF were increased in PDR patients and positively correlated with chemerin/CMKLR1. Additionally, chemerin activated CMKLR1 and aggravated HG-induced cell injury, inflammatory responses, and VEGF expressions in ARPE-19 cells. CONCLUSION: Our study demonstrated that chemerin/CMKLR1 axis aggravated the progression of PDR, which suggested that inhibition of chemerin might serve as a new therapeutic approach to treat PDR.

Low dark current broadband 360-1650 nm ITO/Ag/n-Si Schottky photodetectors.

This work designed an ITO/Ag/n-Si Schottky photodetector with broad wavelength detection and low dark current. The introduction of Ag interfacial layer and post rapid thermal annealing dramatically increase the barrier height of ITO/n-Si Schottky diode by 0.32 eV, leading to the 2300 × reduction of dark current. A well-behaved ITO/Ag (8 nm)/n-Si Schottky diode with a high rectification ratio ( ± 1 V) of 4 × 105 and low dark current (-1 V) of 9.2 nA was achieved. Such low dark current device spontaneously provides high sensitivity for visible/near infrared wavelength detection, in which substantial responsivity for wavelengths from 360 to 1650 nm was realized through both inter-band and internal photoemission. The design here provides an encouraging strategy for monolithically integrated pure Si photodetectors operating at long wavelength up to 1650 nm.

Critical Thinking Disposition of Nurse Practitioners in Taiwan.

BACKGROUND: Critical thinking disposition (CTD) is crucial for nurse practitioners who face complex patient care scenarios. This study explored the CTD of nurse practitioners and related factors. METHOD: The study was a cross-sectional descriptive design. A purposive sample was recruited from a medical center and its hospital branches in central Taiwan. A structured questionnaire was used to collect data from 210 nurse practitioners. RESULTS: The participants obtained the highest average score on systematicity and analyticity. CTD had a significant positive correlation with fundamental knowledge readiness, professional knowledge readiness, and confidence in making clinical decisions. Professional knowledge readiness, education level, and on-the-job training predicted the score of the participants on overall CTD. CONCLUSION: On-the-job training and education level may influence the CTD of nurse practitioners. Providing formal or on-the-job continuing education training to nurse practitioners may help enhance their CTD. J Contin Educ Nurs. 2017;48(9):425-430.

miR-140-5p regulates adipocyte differentiation by targeting transforming growth factor-ß signaling.

Recent emerging studies of miRNAs in adipocyte commitment provide new insights to understand the molecular basis of adipogenesis. The current study indicated that miR-140-5p was altered in primary cultured marrow stromal cells and established progenitor lines after adipogenic and/or osteogenic treatment. miR-140-5p was increased in adipose tissue in db/db obese mice vs. lean mice. Supplementing miR-140-5p activity induced stromal cell ST2 and preadipocyte 3T3-L1 to differentiate into mature adipocytes. Conversely, inhibition of the endogenous miR-140-5p repressed ST2 and 3T3-L1 to fully differentiate. By contrast, knockdown of the endogenous miR-140-5p enhanced osteoblast differentiation. Transforming growth factor-ß receptor I (Tgfbr1) was shown to be a direct target of miR-140-5p. Supplementing miR-140-5p in ST2 reduced the level of TGFBR1 protein, while suppression of endogenous miR-140-5p increased TGFBR1. Overexpression of Tgfbr1 inhibited, whereas knockdown of Tgfbr1 promoted adipogenic differentiation of ST2 cells. Further investigation of mechanisms that control miR-140-5p expression revealed that C/EBPα induced transcriptional activity of the miR-140-5p promoter. Removal of the putative response element of C/EBP from the promoter abolished the enhancement of the promoter activity by C/EBPα, suggesting that C/EBPα transcriptionally controls miR-140-5p expression. Taken together, our study provides evidences that miR-140-5p regulates adipocyte differentiation through a C/EBP/miR-140-5p/TGFBR1 regulatory feedback loop.

miR-223 Regulates Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells Through a C/EBPs/miR-223/FGFR2 Regulatory Feedback Loop.

Several miRNAs have recently been identified to regulate adipocyte or osteoblast differentiation or both. In this study, miR-223 was found to be involved in the reciprocal regulation of adipocyte and osteoblast differentiation. miR-223 was induced in primary cultured mouse marrow stromal cell, mesenchymal line C3H10T1/2 and stromal line ST2 after adipogenic treatment. Conversely, it was reduced in preosteoblast MC3T3-E1 after osteogenic treatment. Supplementing miR-223 levels using synthetic miR-223 mimics significantly suppressed the growth of the C3H10T1/2 and ST2 cells and induced the progenitor cells to fully differentiate into adipocytes, along with induction of adipocyte-specific transcription factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α (C/EBPα), and marker genes aP2 and adipsin. By contrast, depletion of the endogenous miR-223 using synthetic miR-223 inhibitor repressed the progenitor cells to differentiate. The effects of miR-223 on adipocyte formation from ST2 cells were also demonstrated by using lentivirus that overexpresses miR-223. Conversely, supplementing miR-223 blocked ST2 to differentiate into osteoblasts. Fibroblast growth factor receptor 2 (Fgfr2), a critical regulator of osteoblast, was shown to be a direct target of miR-223 by using dual luciferase reporter assay. Knockdown of Fgfr2 in C3H10T1/2 downregulated phosphorylation of ERK1/2 and upregulated expression of C/EBPα and dramatically enhanced the differentiation of the cells into adipocytes. Further investigation of mechanisms that control miR-223 expression demonstrated that C/EBPs induced miR-223 expression through binding to the promoter regions of the miR-223. Taken together, our study provides evidences that miR-223 regulates adipocyte and osteoblast differentiation through a novel C/EBPs/miR-223/FGFR2 regulatory feedback loop.

Fractions and leaching characteristics of mercury in coal.

A huge amount of coal is always stored in open spaces in coal-fired power plants before combustion. Mercury released from coal by rain or flowing water is an environmental risk and can cause contamination of the soil around the storage area. To better understand mercury pollution and to control mercury emission before combustion, it is necessary to determine the mobility and leaching characteristics of mercury from coal. In this study, we collected ten coal samples from one coal-fired power plant and proposed a sequential extraction procedure to get five fractions of mercury for evaluation. Elemental Hg was found as the most dominant fraction, and sulfate Hg was shown to be the second largest fraction. The mercury in the organic and the soluble fractions were not the major fractions, but they should still be considered because of their high mobility.

[Knowledge and attitudes towards second hand smoking among hospitality patronage in five cities in China].

OBJECTIVE: To understand the knowledge and attitudes towards second hand smoking (SHS) among restaurant or bar patronage in five cities in China. METHODS: 405 restaurants and bars were conveniently selected in 5 cities as Beijing, Wuhan, Xi'an, Kunming and Guiyang. From each of these hospitality venues, at least 3 patrons, including one smoker, one female non-smoker and one male nonsmoker were asked to answer a questionnaire on their knowledge and attitudes towards SHS and smoking policies in public places. RESULTS: 43.1% of the respondents had good knowledge on SHS hazards. 65% reported that those who smoked around them had never asked for their permission, and about 60% admitted that they had never asked others to stop smoking in front of them. There were almost two thirds of patrons reporting that they once felt discomfort of SHS in restaurants or bars, nearly half of whom chose to leave the venue to avoid exposure to SHS. Though majority of patrons supported '100% smoke-free hospitals, schools and public vehicles' initiations, the proportions of patrons that supporting '100% smoke-free restaurants and bars' initiations were only 30.0% and 19.8%, respectively. In Beijing, logistic regression model analyses showed that those who supporting 100% smoke-free restaurants and bars tended to be non-smokers, aged 25 years or older and to have had at least college education. Also in Beijing, those being female, having at least college education or non-smokers were more likely to choose restaurants and bars with smoking restrictions. CONCLUSION: Though knowledge on SHS hospitality patronage was still not high or popular for the public to refuse SHS exposure, banning smoking in hospitality venues was public's inclination and would become a trend in public health endeavor.