Nanoscale small extracellular vesicles (sEVs, exosomes) in tears allow us to investigate the multisignatures of diseases. However, the translations of tear sEVs for biomarker discovery and clinical diagnostics are practically limited by low recovery, long processing time, and small sample volume. Here, we report an incorporated tear-exosomes analysis via rapid-isolation system (iTEARS) via nanotechnology to discover the secrets of ocular disorders and systemic diseases. We isolate exosomes rapidly with high yield and purity from a few teardrops (∼10 μL) within 5 min via nanoporous membrane-based resonators for the quantitative detection and biomarker discovery through proteomic and transcriptomic analysis. We have identified 904 proteins, among which 228 proteins are discovered, 426 proteins are detected from exosomes of dry eye disease, and demonstrate CALML5, KRT6A, and S100P for the classification of dry eye disease. We have also investigated 484 miRNAs in tear exosomes and show miR-145-5p, miR-214-3p, miR-218-5p, and miR-9-5p are dysregulated during diabetic retinopathy development. We believe iTEARS can be used for improving molecular diagnostics via tears to identify ocular disorders, systemic diseases, and numerous other neurodegenerative diseases and cancer.
Aims/Introduction Type 2 diabetes mellitus is associated with an increased incidence of osteoporosis and sarcopenia. However, the relationship between osteoporosis and sarcopenia in patients with type 2 diabetes mellitus remains to be unclear. Appendicular skeletal muscle was adjusted by height (appendicular skeletal muscle mass [ASM]/height2) as a marker of sarcopenia. This study aimed to explore the relationship between ASM/height2, osteoporosis and bone mineral density (BMD) in this population. Materials and Methods A total of 192 women and 225 men with type 2 diabetes mellitus were recruited. General information, laboratory and BMD data were collected. Spearman’s correlation, multiple regression analyses and receiver operating characteristic curve analysis were used to explore the correlation between ASM/height2, BMD and bone metabolism markers. Results Spearman’s correlation analysis showed that ASM/height2 had a positive correlation with serum calcium and BMD (r = 0.209–0.404, P < 0.01). In multivariate regression analysis, we found significant correlations between ASM/height2 and total lumbar spine, hip and femur neck BMD. According to the receiver operating characteristic curve, ASM/height2 was the best marker of osteoporosis, with a cut‐off value of 7.87 kg/m2 for men and 5.94 kg/m2 for women. When these cut‐off values were used to identify sarcopenia, the risk of osteoporosis increased 6.036‐fold in men and 4.079‐fold in women, respectively. Conclusions In patients with type 2 diabetes mellitus, ASM/height2 was positively correlated with BMD, and negatively correlated with osteoporosis.
Purpose: To investigate the relationship between aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) and diabetic nephropathy (DN). Patients and Methods: A total of 402 patients with type 2 diabetes mellitus were divided into three groups, such as normoalbuminuria (n = 196), microalbuminuria (n = 131) and macroalbuminuria (n = 75) groups. Basic information and laboratory results were collected. Serum AST/ALT, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10 and interferon-γ (INF-γ) were also measured. DN was defined as microalbuminuria or macroalbuminuria. The estimated glomerular filtration rate (eGFR) was calculated using the following formula: 186 × (serum creatinine) −1.154 × (age) −0.203 × (0.742 if female). Results: The AST/ALT in the macroalbuminuria group was higher than in the microalbuminuria and normoalbuminuria groups. The concentrations of tumor necrosis factor-α (TNFα), IL-2, IL-4, IL-10 and INF-γ in the macroalbuminuria group were significantly higher than those in the two other groups. Multivariate logistical analysis showed that after adjusting confounding factors, TNF-α and high AST/ALT were independent risks for DN and macroalbuminuria. Furthermore, the AST/ALT had significantly positive correlation with TNF-α (r = 0.101, P = 0.048), IL-4 (r = 0.185, P = 0.005) and IL-6 (r = 0.274, P < 0.001) levels. Conclusion:This study showed that high AST/ALT was an independent risk factor for the DN. Additionally, AST/ALT was positively correlated with inflammation cytokines, such as TNF-α, IL-4 and IL-6 levels.
Background Studies analyzing the association between parity and normal-weight metabolic syndrome (MetS) in postmenopausal women of normal weight remain limited, this study aimed to explore the association between parity and MetS among Chinese normal-weight postmenopausal women. Methods In total, 776 normal-weight undiagnosed type 2 diabetes postmenopausal women who visited the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University for a routine health check-up between 1 January 2017 and 31 December 2019 were included in the cross-sectional study. All individuals had fully completed information records encompassing standardized electronic medical records, physical examinations, and biochemical measurements. Metabolic health was defined as fewer than 2 parameters of the MetS were present, in combination with normal weight. Continuous variables which were normally distributed were expressed as means and standard deviation. Comparisons among normally distributed continuous variables were made using one-way ANOVA while that among non-normal distribution parameters were made using Kruskal-Wallis. The association between parity and MetS was analyzed using multivariate logistic regression. All of the analyses were performed with SPSS statistical software (Version 23.0, SPSS, Inc., Chicago, IL, USA) and the statistical software package EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA). Results After adjusting for potential confounding factors including hip circumference, parity was failed to show a significantly relationship with MetS in normal-weight women(P=0.054). Women with a higher parity (≥3) had an increased OR of abdominal obesity, while the OR (95% CI) of the parity 3 group was 2.06 (1.13, 3.77) and that of the parity ≥4 group was 3.08(1.42, 6.66) the P for trend was 0.002 after adjusting for potential confounding factors. No significant differences were detected for other metabolic disorders including high levels of triglycerides (TG), blood pressure, fasting plasma glucose (FPG), and decreased high-density lipoprotein cholesterol (HDL-C) in different parity groups. Conclusions Higher parity was not associated with a higher risk of MetS in normal weight Chinese postmenopausal women. As for the components of MetS, only waist circumference was associated with multiparity even after controlling for hip circumference.
Adefovir dipivoxil (ADV) is one of the most important nucleostide analogues currently in use for the treatment of chronic hepatitis B virus (HBV) infection. Low-dose ADV-induced nephrotoxicity in most cases was reported to be reversible after the discontinuation of ADV or by decreasing the dose of ADV. In our study, we have 5 documented cases of low-dose ADV-induced hypophosphatemia osteomalacia with or without Fanconi syndrome which were diagnosed in our hospital between 2010 and 2017. Three patients were observed to have a full recovery after the discontinuation of ADV. Two patients had persistently elevated urine β 2 -microglobulin levels and out of these two patients, one patient had persistent hypophosphatemia after the cessation of ADV. These cases illustrated that the use of low-dose ADV increased the risk of nephrotoxicity, and in some patients, low-dose ADV-induced nephrotoxicity was not completely reversible. Patients of East Asian origin, especially those with a low body mass index, were prone to a relatively higher risk of developing low-dose ADV-induced nephrotoxicity; therefore, it was worth paying attention to the side effects caused by low-dose ADV.
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