A study of the effect of suboptimal glycemic control on subclinical myocardial systolic function in patients with T2DM

Objective·To explore the relationship between poor blood glucose control and early impaired cardiac function in patients with type 2 diabetes mellitus (T2DM).Methods·Eighty-three patients diagnosed with T2DM in Jiading Branch of Shanghai General Hospital from June 2021 to March 2022 were selected and divided into two groups according to the level of hemoglobin A1c (HbA1c): satisfactory control of glycaemia (SCG) group and less satisfactory control of glycaemia (LSCG) group. Fifty-four subjects were in the control group. Echocardiography was performed to obtain left ventricular structural and functional parameters and left ventricular subendocardial, medial and subepicardial global longitudinal strain (GLS): GLSendo, GLSmid, and GLSepi. The parameters were compared by using analysis of variance. The correlation analysis was performed by Pearson correlation analysis and multiple linear regression analysis. The diagnostic performance of longitudinal strain in differentiating subclinical myocardial dysfunction in patients with T2DM was analyzed by receiver operator characteristic (ROC) curve.Results·The thickness of the ventricular septum and the posterior wall of the left ventricle were thicker in the LSCG group than in the SCG group and the control group (all P0.05). Compared with the control group, the left ventricular diastolic function index E/e (early peak flow velocity by Doppler/early and atrial diastolic velocity of the mitral annulus by tissue Doppler imaging) was higher in both the LSCG group and the SCG group (all P 0.05). There was no significant difference in left ventricular ejection fraction among the three groups (P>0.05). Compared with LSCG group, GLSendo, GLSmid and GLSepi were higher in the SCG group and control group (all P0.05). HbA1c was an independently negative factor of GLSmid and GLSepi (β= -0.198 and -0.239, all P<0.05). GLSendo, GLSmid and GLSepi had moderate diagnostic performance between the LSCG group and SCG group, with areas under the curve (AUC) of 0.754 (95%CI 0.624‒0.884), 0.755 (95%CI 0.624‒0.885), and 0.751 (95%CI 0.619‒0.882), respectively.Conclusions·T2DM patients with unsatisfactory glycemic control have reduced myocardial contractility, and this subclinical myocardial damage is independently negatively correlated with the level of HbA1c

Altered interictal cerebral blood flow in generalized tonic-clonic seizure: an arterial spin labeling based MRI study

Objective To study the alteration of interictal cerebral blood flow (CBF) of patients with generalized tonic-clonic seizure (GTCS) by pulsed arterial spin labeling (PASL), and uncover the neuropathophysiological mechanism of GTCS. Methods Twenty⁃nine patients with GTCS were included in this study, and the same number of age- and gender-matched healthy volunteers were set as controls. PASL data of all subjects were obtained on a Siemens MAGNETOM Trio 3.0T scanner. The regional cerebral blood flow of GTCS patients were compared with the controls by two-sample t-test. Results Compared with the controls, GTCS patients presented decreased regional cerebral blood flow in bilateral thalumus, brainstem and cerebellum, and also a part of cortical area of the right precuneus (P < 0.05, for all). The alteration of interictal regional cerebral blood flow in bilateral thalumus was not significantly related to seizure duration (r = -0.090, P = 0.643) and seizure frequency (r = -0.115, P = 0.551). Conclusion The decreased regional cerebral blood flow in bilateral thalumus, brainstem and cerebellum indicates the "mesencephalic epilepsy" theory in GTCS, which may contribute to the understanding of the pathophysiological mechanism of GTCS. DOI：10.3969/j.issn.1672-6731.2011.04.01

Diagnosis and classification in MRI of brucellar spondylitis

Objective: To explore the magnetic resonance imaging (MRI) features of patients with brucellar spondylitis and try to classify them depending on the MRI findings. Material and methods: 67 patients (male&female: 50&17) with brucellar spondylitis were recruited in this study. MRI examinations were performed in all patients. Firstly, MRI data were analyzed by two senior radiologists. Secondly, according to the imaging findings, patients were divided into different types. Results: In all 67 patients with spinal brucellosis, 5 cases only had paravertebral soft tissue involved, 62 cases showed abnormal signal in single or multiple adjacent vertebrae. Thirty-five patients focused on the L4 vertebral involvement. 18 cases had appendage involvement. 27 cases hand intervertebral disc narrowing and cystic signal. Paravertebral, epidural and psoas abscesses were detected in 35, 20 and 8 cases. Patients were grouped according to MRI findings. The vertebral inflammatory type was the most frequently type with the rate of 35.8%, followed by discitis type 32.9%, adnexitis type 11.9%, paravertebral and psoas abscess type 11.9% and paravertebral soft tissue type 7.5%. Conclusion: It is not difficult to diagnose brucellar spondylitis in MRI findings based on clinical background and laboratory tests. According to the performance of MRI, five types can be classified

Ultrasound-enhanced fluorescence imaging and chemotherapy of multidrug-resistant tumors using multifunctional dendrimer/carbon dot nanohybrids

Development of innovative nanomedicine enabling enhanced theranostics of multidrug-resistant (MDR) tumors remains to be challenging. Herein, we report the development of a newly designed multifunctional yellow-fluorescent carbon dot (y-CD)/dendrimer nanohybrids as a platform for ultrasound (US)-enhanced fluorescence imaging and chemotherapy of MDR tumors. Generation 5 (G5) poly(amidoamine) dendrimers covalently modified with efflux inhibitor of d-α-tocopheryl polyethylene glycol 1000 succinate (G5-TPGS) were complexed with one-step hydrothermally synthesized y-CDs via electrostatic interaction. The formed G5-TPGS@y-CDs complexes were then physically loaded with anticancer drug doxorubicin (DOX) to generate (G5-TPGS@y-CDs)-DOX complexes. The developed nanohybrids display a high drug loading efficiency (40.7%), strong y-CD-induced fluorescence emission, and tumor microenvironment pH-preferred DOX release profile. Attributing to the DOX/TPGS dual drug design, the (G5-TPGS@y-CDs)-DOX complexes can overcome the multidrug resistance (MDR) of cancer cells and effectively inhibit the growth of cancer cells and tumors. Furthermore, the introduction of US-targeted microbubble destruction technology was proven to render the complexes with enhanced intracellular uptake and anticancer efficacy in vitro and improved chemotherapeutic efficacy and fluorescence imaging of tumors in vivo due to the produced sonoporation effect. The developed multifunctional dendrimer/CD nanohybrids may represent an advanced design of nanomedicine for US-enhanced theranostics of different types of MDR tumors

M3 muscarinic acetylcholine receptors regulate epithelial–mesenchymal transition, perineural invasion, and migration/metastasis in cholangiocarcinoma through the AKT pathway

Abstract Background Cholangiocarcinoma is a highly malignant tumor type that is not sensitive to radiotherapy or chemotherapy due to aggressive perineural invasion and metastasis. Unfortunately, the mechanisms underlying these processes and the signaling factors involved are largely unknown. In this study, we analyzed the role of M3 muscarinic acetylcholine receptors (M3-mAChR) in cell migration, perineural invasion, and metastasis during cholangiocarcinoma. Methods We assessed 60 human cholangiocarcinoma tissue samples and 30 normal biliary tissues. Immunohistochemical staining was used to detect M3-mAChR expression and the relationship between expression and clinical prognosis was evaluated. The biological functions of M3-mAChR in cholangiocarcinoma cell migration, perineural invasion, and epithelial–mesenchymal transition (EMT) were investigated using the human cholangiocarcinoma cell lines FRH0201 and RBE in conjunction with various techniques, including agonist/antagonist treatment, RNA interference, M3-mAChR overexpression, dorsal root ganglion co-culturing, immunohistochemistry, western blotting, etc. Results M3-mAChR were highly expressed in cholangiocarcinoma tissue and expression was closely related to differentiation and lymphatic metastasis, affecting patient survival. Treatment with the M3-mAChR agonist pilocarpine and M3-mAChR overexpression significantly promoted migration and perineural invasion, while the M3-mAChR antagonist atropine blocked these effects. Similarly, M3-mAChR knock-down also weakened cell migration and perineural invasion. The expression of phosphatase and tensin homolog, AKT, E-cadherin, vimentin, and Snail, which are components of the phosphatidylinositol 3-kinase/AKT signaling pathway and EMT, were altered by pilocarpine, and these effects were again blocked by atropine. Notably, AKT knock-down decreased M3-mAChR expression and reversed the downstream effects of this receptor. Conclusions M3-mAChR are involved in tumor cell migration, perineural invasion, and EMT during cholangiocarcinoma, and these effects are modulated via the AKT signaling pathway