These findings demonstrate that anthocyanin supplementation exerts beneficial metabolic effects in subjects with type 2 diabetes by improving dyslipidemia, enhancing antioxidant capacity, and preventing insulin resistance. This trial was registered at www.clinicaltrials.gov as NCT02317211.

Abstract-Interaction of the platelet receptor glycoprotein (GP) Ib-V-IX with von Willebrand factor exposed at a site of vascular injury is an essential step in the initiation of a hemostatic plug. Proteolytic cleavage (shedding) of the GPIb␣ subunit was first described Ͼ25 years ago, the protease mediating this event as well as its physiological function, however, have not been elucidated. We reported recently that shedding of GPIb␣ induced by platelet storage or mitochondrial injury involves a platelet-derived metalloproteinase(s). Here we show that GPIb␣ shedding in response to mitochondrial injury or physiological activation is inhibited in platelets obtained from chimeric mice, which express inactive tumor necrosis factor-␣ converting enzyme (TACE ⌬Zn/⌬Zn ) in blood cells only. Shedding was also inhibited in mouse and human platelets in the presence of 2 potent TACE inhibitors: TAP1 and TMI-1. Our data further suggest that TACE is important in the regulation of GPIb␣ expression in vivo because we observed an Ϸ90% reduction in soluble GPIb␣ (glycocalicin) in plasma of TACE ⌬Zn/⌬Zn chimeras as well as significantly increased levels of GPIb␣ on circulating platelets. In contrast, shedding of P-selectin from activated platelets was not affected by the mutation in TACE. Damaged TACE ⌬Zn/⌬Zn platelets were further characterized by a markedly improved post-transfusion recovery and hemostatic function in mice. In conclusion, our data demonstrate that TACE is expressed in platelets and that it is the key enzyme mediating shedding of GPIb␣. Key Words: platelets Ⅲ TACE Ⅲ GPIb␣, shedding C ellular activation often results in the rapid proteolysis of a wide range of transmembrane proteins such as growth factors/cytokines, growth factor/cytokine receptors, and adhesion molecules. This process, known as ectodomain shedding, regulates many cellular functions and has been implicated in pathologies such as Alzheimer's disease and cancer. 1 The majority of these shedding events are mediated by zinc-dependent proteinases, most importantly members of the matrix metalloproteinase (MMP) 2 and a disintegrin and metalloproteinase (ADAM) 3 family of proteinases. Initially identified as a sheddase for tumor necrosis factor-␣ (TNF-␣), TNF-␣-converting enzyme (TACE; ADAM17) was also shown to mediate the release of many other cell surface transmembrane proteins, including adhesion molecules such as L-selectin and vascular cell adhesion molecule 1 (VCAM-1). 4 -6 Inactivation of the metalloproteinase activity of TACE by targeted deletion of the Zn 2ϩ -binding domain in mice (TACE ⌬Zn/⌬Zn ) results in perinatal lethality, demonstrating the importance of ectodomain shedding in vivo. 4 In platelets, proteolytic cleavage has been identified as a key mechanism to regulate the surface expression of a variety of adhesion receptors, including P-selectin, CD40 ligand, and the glycoprotein (GP) V and GPIb␣ subunits of the von Willebrand factor receptor complex, GPIb-V-IX. 7-9 GPIb-V-IX plays an important role in the adhesion of circulating platelet...

Thyroid nodules are very common all over the world, and China is no exception. Ultrasound plays an important role in determining the risk stratification of thyroid nodules, which is critical for clinical management of thyroid nodules. For the past few years, many versions of TIRADS (Thyroid Imaging Reporting and Data System) have been put forward by several institutions with the aim to identify whether nodules require fine-needle biopsy or ultrasound follow-up. However, no version of TIRADS has been widely adopted worldwide till date. In China, as many as ten versions of TIRADS have been used in different hospitals nationwide, causing a lot of confusion. With the support of the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association, the Chinese-TIRADS that is in line with China's national conditions and medical status was established based on literature review, expert consensus, and multicenter data provided by the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound.

Objective: We aimed to investigate the relationship between clinical characteristics, outcomes and the severity of severe acute respiratory syndrome coronavirus 2 pneumonia. Methods: We performed a systematic review and meta-analysis using PubMed, Embase, and Cochrane Library databases to assess the clinical characteristics and outcomes of confirmed COVID-19 cases and compared severe (ICU) and nonsevere (non-ICU) groups. Results: We included 12 cohort studies including 2,445 patients with COVID-19. Compared with nonsevere (non-ICU) patients, severe (ICU) disease was associated with a smoking history (P = .003) and comorbidities including chronic obstructive pulmonary disease (OR = 5.08, P < .001), diabetes (OR = 3.17, P < .001), hypertension (OR = 2.40, P < .001), coronary heart disease (OR = 2.66, P < .001), cerebrovascular diseases (OR = 2.68, P = .008), and malignancy (OR=2.21, P = .040). We found significant differences between the 2 groups for fever, dyspnea, decreased lymphocyte and platelet counts, and increased leukocyte count, C-creative protein, procalcitonin, lactose dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine levels (P < .05). Significant differences were also observed for multiple treatments (P < .05). Patients in the severe (ICU) group were more likely to have complications and had a much higher mortality rate and lower discharge rate than those with nonsevere (non-ICU) disease (P < .05). Conclusions: Investigation of clinical characteristics and outcomes of severe cases of COVID-19 will contribute to early prediction, accurate diagnosis, and treatment to improve the prognosis of patients with severe illness.

ObjectivesTo identify metabolic markers that can classify patients with osteoarthritis (OA) into subgroups.DesignA case-only study design was utilised.ParticipantsPatients were recruited from those who underwent total knee or hip replacement surgery due to primary OA between November 2011 and December 2013 in St. Clare's Mercy Hospital and Health Science Centre General Hospital in St. John's, capital of Newfoundland and Labrador (NL), Canada. 38 men and 42 women were included in the study. The mean age was 65.2±8.7 years.Outcome measuresSynovial fluid samples were collected at the time of their joint surgeries. Metabolic profiling was performed on the synovial fluid samples by the targeted metabolomics approach, and various analytic methods were utilised to identify metabolic markers for classifying subgroups of patients with OA. Potential confounders such as age, sex, body mass index (BMI) and comorbidities were considered in the analysis.ResultsTwo distinct patient groups, A and B, were clearly identified in the 80 patients with OA. Patients in group A had a significantly higher concentration on 37 of 39 acylcarnitines, but the free carnitine was significantly lower in their synovial fluids than in those of patients in group B. The latter group was further subdivided into two subgroups, that is, B1 and B2. The corresponding metabolites that contributed to the grouping were 86 metabolites including 75 glycerophospholipids (6 lysophosphatidylcholines, 69 phosphatidylcholines), 9 sphingolipids, 1 biogenic amine and 1 acylcarnitine. The grouping was not associated with any known confounders including age, sex, BMI and comorbidities. The possible biological processes involved in these clusters are carnitine, lipid and collagen metabolism, respectively.ConclusionsThe study demonstrated that OA consists of metabolically distinct subgroups. Identification of these distinct subgroups will help to unravel the pathogenesis and develop targeted therapies for OA.