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Objective:Pretibial myxedema (PTM) is a localized myxedema characterized by excessive dermal hya-luronan (HA) deposition and elevated serum TSH receptor antibody (TRAb). In this study, we investigated the effects of TRAb and its subtypes, stimulating antibody [TSAb (M22)] and inhibitory antibody[TBAb (K1-70)], on the synthesis of hyaluronic acid produced by PTM primary dermal fibroblasts.Methods:Normal and PTM dermal fibroblasts were isolated and stimulated with M22, K1-70, and IgG from patients respectively. HA concentration in the supernatant before and after stimulation was tested by ELISA. The protein level and phosphorylation variation of CEMIP, HAS2 and PI3K-AKT pathway were detected by Western blot.Results:IgG from patients (TRAb 8.4 IU/L) significantly stimulated the extracellular accumulation of HA in PTM primary fibroblasts. Similarly, both M22 and K1-70 also upregulated HA level in the supernatant, though K1-70 seemed much more effecitve. After treatment with IgG, M22, and K1-70, the expression of HAS2 increased and the expression of CEMIP decreased; meanwhile, p-PI3K and p-AkT increased. Among them, further study on K1-70, promoting HA production by regulating PI3K-AkT signal pathway could be inhibited by PI3K inhibitor (LY294002).Conclusion:TSAb (M22) and TBAb (K1-70), especially TBAb, increase HAS2 and inhibit CEMIP expression by activating PI3-AKT signaling pathway in PTM fibroblasts, leading to increased extracellular HA level.
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Objective To investigate the major risk factors for posterior circulation stroke and the clinical and imaging features of posterior circulation stroke patients with diabetes.Methods The patients with acute cerebral infarction were enrolled.The clinical data of patients with posterior circulation and anterior circulation stroke were compared.The patients with posterior circulation stroke were further divided into either a diabetic group or a non-diabetic group,and the vascular risk factors and imaging features of both groups were compared.The patients with posterior circulation stroke were divided into proximal segment,middle segment and distal segment and mixed groups according to the distribution of vascular lesions.The correlations between diabetes and each group and the imaging features were analyzed.Results A total of 328 patients with posterior circulation stroke (male 194,the diabetic group 108) and 336 patients with anterior circulation stroke (male 214,the diabetes group 59)were enrolled.The proportions of patients with diabetes (32.9％ vs.21.7％ ; x2 =10.501,P =0.001),hyperlipidemia (60.1％ vs.47.9％ ;x2 =9.852,P =0.002),previous stroke or transient ischemic attack (TIA) (29.0％ vs.22.0％ ;x2 =4.213,P =0.040) in the posterior circulation ischemic stroke group were significantly higher than those in the anterior circulation ischemic stroke group,and the proportion of smoking patients was significantly lower than that in the anterior circulation ischemic stroke group (18.3％ vs.26.2％ ; x2 =5.977,P =0.014).The levels of total cholesterol (4.72 ±1.07 mmol/L vs.4.56 ± 0.98 mmol/L; t =2.079,P =0.038),triglycerides (1.54 ± 1.07 mmol/L vs.1.33±0.71 mmol/L; t=3.085,P=0.002) and low-density lipoprotein cholesterol (2.91±0.90 mmol/L vs.2.75 ±0.80 mmol/L; t =2.373,P =0.018) were significantly higher than those in the anterior circulation ischemic stroke group,and the level of high-density lipoprotein cholesterol was significantly lower than that in the anterior circulation ischemic stroke group (1.13 ± 0.31 mmol/L vs.1.18 ±0.32 mmol/L; t =2.045,P=0.041).Multivariate logistic regression analysis showed that diabetes (odds ratio [OR] 1.560,95％ confidence interval [CI] 1.086-2.239; P =0.016) and previous stroke or TIA history (OR 1.455,95％ CI 1.013-2.090; P =0.042) were the independent risk factors for posterior circulation ischemic stroke.In patients with posterior circulation ischemic stroke,the patient's proportions of hyperllpidemia (66.7％ vs.55.5％ ;x2 =5.069,P =0.024) and drinking (13.0％ vs.4.5％;x2 =7.568,P=0.006) in the diabetic group (n =108) were significantly higher than those in the non-diabetic group (n =220); the proportion of atrial fibrillation patients was significantly lower than that in the non-diabetic group (3.7％ vs.11.4％ ;x2 =5.274,P =0.022).The levels of triglycerides (1.70 ± 0.93 rnmol/L vs.1.45 ± 1.11 mmol/L; t =1.989,P =0.048),fasting glucose (8.46 ± 2.96) mmol/L vs.5.30± 0.96 mmol/L; t=10.706,P=0.000) and glycosylated hemoglobin (8.36％ ± 1.94％ vs.6.07％ ± 0.55％ ; t =10.576,P =0.000) in the diabetic group were significantly higher than those in the non-diabetic group.The proportion of patients with large artery atherosclerosis stroke in the diabetic group was significantly higher than that in the non-diabetic group (73.1％ vs.60.0％; x2=5.457,P=0.019); the proportion of the patients with cardioembolism was significantly lower than that of the non-diabetic group (2.8％ vs.9.1％;x2 =4.428,P =0.035).The proportion of patients with posterior circulation middle segment infarction in the diabetic group was significantly higher than that of the non-diabetic group (49.1％ vs.31.4％ ;x2 =9.726,P =0.002).The proportions of the patients with brainstem infarction (60.2％ vs.48.2％ ;x2 =4.182,P =0.041) and single brainstem infarction (55.6％ vs.30.5％ ;x2 =19.235,P =0.000) in the diabetic group were significantly higher than those in the non-diabetic group.In patients with single brainstem infarction,the proportions of the patients with pontine infarction (43.5％ vs.25.9％ ;x2 =10.374,P =0.001) and medulla oblongata infarction (7.4％ vs.1.8％ ; P =0.023) in the diabetic group were significantly higher than those in the non-diabetic group.Conclusions Diabetes and previous stroke or TIA history are the independent risk factor for posterior circulation stroke.Diabetes is closely associated with brainstem infarction,and it is more likely to result in pontine infarction.
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With the improvement of radiation therapy technology and the comprehensive treatment of malignant tumors,the survival time of patients with malignant tumors is gradually extended.In recent years,carotid stenosis and cerebrovascular disease complications after radiation therapy have received increasing attention.Existing studies have shown that carotid stenosis after radiation therapy is not only associated with atherosclerosis,it is likely to be an independent vascular lesion.This article reviews the correlation between head,neck and cerebral ischemic events,characteristics and mechanisms of vascular injury after radiation therapy,as well as the risk factors for carotid stenosis,clinical manifestations,and diagnosis and treatment methods after radiation therapy.
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The softening of fleshy fruits, such as tomato (Solanum lycopersicum), during ripening is generally reported to result principally from disassembly of the primary cell wall and middle lamella. However, unsuccessful attempts to prolong fruit firmness by suppressing the expression of a range of wall-modifying proteins in transgenic tomato fruits do not support such a simple model. 'Delayed Fruit Deterioration' (DFD) is a previously unreported tomato cultivar that provides a unique opportunity to assess the contribution of wall metabolism to fruit firmness, since DFD fruits exhibit minimal softening but undergo otherwise normal ripening, unlike all known nonsoftening tomato mutants reported to date. Wall disassembly, reduced intercellular adhesion, and the expression of genes associated with wall degradation were similar in DFD fruit and those of the normally softening 'Ailsa Craig'. However, ripening DFD fruit showed minimal transpirational water loss and substantially elevated cellular turgor. This allowed an evaluation of the relative contribution and timing of wall disassembly and water loss to fruit softening, which suggested that both processes have a critical influence. Biochemical and biomechanical analyses identified several unusual features of DFD cuticles and the data indicate that, as with wall metabolism, changes in cuticle composition and architecture are an integral and regulated part of the ripening program. A model is proposed in which the cuticle affects the softening of intact tomato fruit both directly, by providing a physical support, and indirectly, by regulating water status.
