Cardiac cine magnetic resonance fingerprinting for combined ejection fraction,T1 and T2 quantification

This study introduces a technique called cine magnetic resonance fingerprinting (cine‐MRF) for simultaneous T₁, T₂ and ejection fraction (EF) quantification. Data acquired with a free‐running MRF sequence are retrospectively sorted into different cardiac phases using an external electrocardiogram (ECG) signal. A low‐rank reconstruction with a finite difference sparsity constraint along the cardiac motion dimension yields images resolved by cardiac phase. To improve SNR and precision in the parameter maps, these images are nonrigidly registered to the same phase and matched to a dictionary to generate T₁ and T₂ maps. Cine images for computing left ventricular volumes and EF are also derived from the same data. Cine‐MRF was tested in simulations using a numerical relaxation phantom. Phantom and in vivo scans of 19 subjects were performed at 3 T during a 10.9 seconds breath‐hold with an in‐plane resolution of 1.6 x 1.6 mm² and 24 cardiac phases. Left ventricular EF values obtained with cine‐MRF agreed with the conventional cine images (mean bias ?1.0%). Average myocardial T₁ times in diastole/systole were 1398/1391 ms with cine‐MRF, 1394/1378 ms with ECG‐triggered cardiac MRF (cMRF) and 1234/1212 ms with MOLLI; and T₂ values were 30.7/30.3 ms with cine‐MRF, 32.6/32.9 ms with ECG‐triggered cMRF and 37.6/41.0 ms with T₂‐prepared FLASH. Cine‐MRF and ECG‐triggered cMRF relaxation times were in good agreement. Cine‐MRF T₁ values were significantly longer than MOLLI, and cine‐MRF T₂ values were significantly shorter than T₂‐prepared FLASH. In summary, cine‐MRF can potentially streamline cardiac MRI exams by combining left ventricle functional assessment and T₁‐T₂ mapping into one time‐efficient acquisition.     

蛋白激酶CβⅡ诱导上皮-间质转化及血管新生促进肝癌发展

目的 探讨蛋白激酶CβⅡ（PKCβⅡ）在肝细胞癌(HCC)发展中的作用机制。方法 免疫印迹法观察PKCβⅡ在肝细胞系L02和肝癌细胞系SK-hep1、HepG2、BEL-7404、7721、Hep3B和huh7中的表达，构建稳定高表达PKCβⅡ的细胞系，倒置相差显微镜下观察细胞形态变化，免疫荧光观察E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）表达的变化；通过免疫印迹法、实时定量聚合酶链反应(Real-time PCR)和放线菌酮（CHX）追踪实验，观察PKCβⅡ调控E-cadherin、N-cadherin和Snail表达的分子机制；小室迁移和侵袭实验(transwell assay)以及裸鼠尾静脉注射观察PKCβⅡ对肝癌细胞转移的影响；成管实验观察PKCβⅡ对人脐静脉内皮细胞（HUVECs）血管形成能力的影响，酶联免疫吸附法（ELISA）观察PKCβⅡ对肝癌细胞上清中血管内皮生长因子A（VEGFA）含量的影响。结果 PKCβⅡ在肝癌细胞系中的表达高于肝细胞系L02，PKCβⅡ促进肝癌细胞形态从鹅卵石样上皮细胞向梭行间质样细胞的转变，通过mRNA水平下调E-cadherin（P<0.05）和上调N-cadherin（P<0.01）的蛋白表达，通过翻译水平上调Snail蛋白表达，PKCβⅡ还促进了肝癌细胞的迁移、侵袭（P<0.01）以及VEGFA的分泌（P<0.01）和血管新生（P<0.01）。结论 蛋白激酶CβⅡ诱导上皮-间质转化及血管新生在肝癌的发展中有重要作用。     

Propofol upregulates miR-320a and reduces HMGB1 by downregulating ANRIL to inhibit PTC cell malignant behaviors

BackgroundOur previous study states that propofol suppresses proliferation and migration of papillary thyroid cancer (PTC) cells by downregulation of lncRNA ANRIL. This study intended to probe the downstream mechanism of ANRIL in PTC with potential microRNAs (miR) and genes.MethodsANRIL expression was detected in normal thyroid epithelial cells (Nthy-ori 3-1) and PTC cells (TPC-1, FTC-133, K1 and BCPAP). ANRIL expression was inhibited in TPC-1 and BCPAP cells to explore the effects of si-ANRIL in PTC malignant behaviors. The gain-and loss-of functions of ANRIL/miR-320a were performed to measure their roles in PTC. Levels of ANRIL, miR-320a, HMGB1, apoptosis- and Wnt/β-catenin and NF-κB pathways-related proteins were measured. Dual-luciferase reporter gene assay and RNA pull-down assay were applied to verify ANRIL/miR-320a/HMGB1 relation. si-ANRIL was transplanted into xenograft tumors in nude mice.ResultsANRIL was upregulated in TPC-1 and BCPAP cells. miR-320a targeted HMGB1, and ANRIL bound to miR-320a. In TPC-1 and BCPAP cells, si-ANRIL prevented PTC cell malignant behaviors, and inactivated the Wnt/β-catenin and NF-κB pathways; while si-ANRIL + miR-320a inhibition showed opposite trends. Overexpressing miR-320a promoted malignant behaviors of TPC-1 cells. In 6 μg/mL propofol-treated TPC-1 cells, miR-320a inhibition weakened propofol’s inhibitory effects on PTC cell growth. After ANRIL inhibition, the volume and weight of xenograft tumors were decreased.ConclusionPropofol upregulated miR-320a and reduced HMGB1 by downregulating ANRIL and inactivating the Wnt/β-catenin and NF-κB pathways, thus preventing PTC cell malignant behaviors. This study may offer new insights in PTC prevention and treatment.     

The Proportion of Vδ1T Cells in Peripheral Blood Correlated with Prognosis of Sepsis

Background: Sepsis is a serious condition with a high mortality rate, and septic patients often have organ dysfunction, low tissue perfusion and hypoxia, lactic acidosis, oliguria, or functional brain changes.Objective: To observe the number and the function of Vδ1T cells in peripheral blood of septic patients, to analyze the clinical significance of detecting Vδ1T cells, and to clarify the correlation of their presence with the prognosis of sepsis.Methods: The basic data of the septic patients were recorded at admission. The immunosuppressive function–related molecules on the surface of Vδ1T cells were detected, and the immunosuppressive function of Vδ1T cells was also evaluated.Results: Compared with the healthy controls, the proportion of Vδ1T cells in the blood of septic patients significantly decreased (P<0.01). The proportion of Vδ1T cells in septic patients correlated with the patients’ condition (P<0.05). The expression of glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) on the surface of Vδ1T cells in the blood of septic patients significantly increased (P<0.01). The increase of Vδ1T cells in septic patients had inhibitory effects on T cell proliferation and interferon (IFN)-γ secretion. These findings implied that the immunosuppression of Vδ1Tcells in the peripheral blood of septic patients was significantly higher than that of the healthy controls (P<0.01).Conclusion: Changes in Vδ1T cells in septic patients were closely related to the patient’s condition and prognosis.     

Endothelin-1 induces chondrocyte senescence and cartilage damage via endothelin receptor type B in a post-traumatic osteoarthritis mouse model

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Diabetes treatment and hypoglycaemic episodes in elderly patients at nursing homes in Uppsala County

Aim: The aim of this study was to examine the situation for elderly patients with diabetes living in nursing homes with regard to diabetes treatment, clinical variables, and vascular complications associated with diabetes. A second aim was to evaluate if the patients were at risk of hypoglycaemia.

Methods: This was a cross-sectional study including diabetes patients from all 30 nursing homes in Uppsala County, Sweden. Current antidiabetic medications, HbA_1c, hypoglycaemic events, and diabetes complications were registered from the medical records. The patients were stratified into a general group and divided into three groups according to HbA_1c (<52, 52–73, and >73?mmol/mol).

Results: Of 1,350 individuals, 218 patients were identified with diabetes mellitus. The diabetes duration was 11.2?±?9.4 years and their serum HbA_1c concentration 56.0?±?1.2?mmol/mol. Hypoglycaemic events were reported in 24% of the diabetic individuals, and 43.1% of them had HbA_1c <52?mmol/mol (mean value 44.0?±?1.1?mmol/mol). Of these, 36% were taking antidiabetic drugs. Another 35.8% of the patients had HbA_1c values between 52–73?mmol/mol (mean value 60.0?±?1.1?mmol/mol), and 82% of these patients were taking antidiabetic drugs. Almost 80% of the diabetic patients had either micro- or macrovascular complications, with diabetes duration as an association for both micro- or macrovascular complications and hypoglycaemic events.

Conclusions: A reduction of the use of antidiabetic drugs with follow-up of HbA_1c level should be considered, especially for multimorbid elderly patients with low HbA_1c and hypoglycaemia.     

Serum matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-1 levels in autoimmune encephalitis

ObjectiveSome pediatric patients with autoimmune encephalitis (AE) experience sequelae in spite of immunotherapy. In this study, we aimed to evaluate the association of serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels with the neurological prognosis of AE.MethodsWe retrospectively included 13 patients with AE who had been referred to Saitama Children’s Medical Center from February 2011 to May 2019. We compared serum MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio in the acute period (within 30 days from the onset of AE) and subacute period (30-day period following the acute period). We also compared these biomarker levels between patients with (group A) and without sequelae (group B). Sequelae were evaluated at discharge or the last visit.ResultsGroup A (median age, 7.8 years; range, 5.3–10.7 years) and group B (median age, 13.3 years; range, 11.1–15.4 years) had 6 patients each; 1 patient was excluded because the time of AE onset was unknown. In the acute period, there were no significant differences in MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio between groups A and B. In the subacute period, serum MMP-9/TIMP-1 ratio was higher in group A than in group B (p < 0.01). There were no significant differences in MMP-9 and TIMP-1 levels between groups A and B.ConclusionsPatients with sequelae of AE showed a high MMP-9/TIMP-1 ratio in the subacute period. Our study demonstrates that elevation of serum MMP-9/TIMP-1 ratio in the subacute period may be a predictive factor of sequelae of AE.     

Type 1 diabetes mellitus associated or not with primary hypothyroidism and women’s fertility

Abstract

The aim of this study is to evaluate the prevalence of infertility and other reproductive parameters in women with type 1 diabetes mellitus (DM1) with and without primary hypothyroidism (PH). This is a cross-sectional study conducted at Division of Endocrinology. We evaluated 110 female, aged over 18 years, 79 had DM1 and 31 had DM1 plus PH. They were interviewed to obtain data on their gynecological and obstetric history; medical charts were reviewed to determine the characteristics of the diseases and to assess clinical/laboratory data. Infertility was defined as 12 months of unprotected sexual intercourse without conception. We used the chi-square and Mann–Whitney’s tests, and logistic regression analysis. The prevalence of infertility in the total sample was 24.5%, no differences were found between groups regarding obstetric outcomes and gynecologic variables. Factors associated with infertility were microvascular complication (OR: 11.36; 95% CI: 2.488–52.632; p?=?.029), polycystic ovary syndrome (OR: 9.80; 95% CI: 2.247–43.478; p?=?.016), PH (OR: 3.38; 95% CI: 1.078–10.638; p?=?.047), and older age at onset of DM1 (OR: 1.12; 95% CI: 1.029–1.215; p?=?.019). The presence of PH in women with DM1 was a predictive factor for infertility. Women with DM1 showed poorer reproductive outcomes compared to the general population.