INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

脂质蓄积指数和内脏脂肪指数对成年人代谢综合征的预测价值研究

背景　脂质蓄积指数（LAP）和内脏脂肪指数（VAI）是反映个体脂肪分布及内脏脂肪蓄积程度的重要指标，与肥胖相关的慢性代谢性疾病关系密切。目的　探讨LAP和VAI与成年人代谢综合征（MS）的相关性，并评估LAP、VAI对MS的预测价值。方法　纳入2018年9月至2019年5月在中日友好医院体检中心进行体检的708例受试者，其中MS患者249例（MS组），非MS患者459例（非MS组），比较两组患者LAP、VAI及相关生化指标。根据LAP、VAI四分位数将受试者进行分组（L1组、L2组、L3组、L4组各177例；V1组、V2组、V3组、V4组各177例），比较各组MS及其组分发生率。采用多因素Logistic回归分析计算不同LAP、VAI受试者MS的发生风险，并分别绘制不同性别LAP、VAI、腰围（WC）、体质指数（BMI）预测MS发生风险的受试者工作特征（ROC）曲线。结果　LAP和VAI与成年人MS发生率呈高强度正相关（Cramer's V=0.585、0.577）。多因素Logistic回归分析结果显示，在调整各危险因素后，L3组、L4组MS发生风险仍高于L1组，V3组、V4组MS发生风险仍高于V1组（P<0.001）。ROC曲线分析结果显示，男性LAP、VAI预测MS发生风险的ROC曲线下面积（AUC）分别为0.831〔95%CI（0.795，0.867）〕、0.825〔95%CI（0.788，0.863）〕，临界值分别为52.03、1.99；女性LAP、VAI预测MS发生风险的AUC分别为0.887〔95%CI（0.834，0.940）〕、0.886〔95%CI（0.827，0.945）〕，临界值分别为54.84、2.54。结论　LAP、VAI与成年人MS发生率呈高强度正相关，随着LAP、VAI增高，MS发生风险亦增高；LAP、VAI对MS有良好的预测价值，联合WC和BMI能有效预测MS。     

Rubik’s Cube+: A self-supervised feature learning framework for 3D medical image analysis

Due to the development of deep learning, an increasing number of research works have been proposed to establish automated analysis systems for 3D volumetric medical data to improve the quality of patient care. However, it is challenging to obtain a large number of annotated 3D medical data needed to train a neural network well, as such manual annotation by physicians is time consuming and laborious. Self-supervised learning is one of the potential solutions to mitigate the strong requirement of data annotation by deeply exploiting raw data information. In this paper, we propose a novel self-supervised learning framework for volumetric medical data. Specifically, we propose a pretext task, i.e., Rubik’s cube+, to pre-train 3D neural networks. The pretext task involves three operations, namely cube ordering, cube rotating and cube masking, forcing networks to learn translation and rotation invariant features from the original 3D medical data, and tolerate the noise of the data at the same time. Compared to the strategy of training from scratch, fine-tuning from the Rubik’s cube+ pre-trained weights can remarkablely boost the accuracy of 3D neural networks on various tasks, such as cerebral hemorrhage classification and brain tumor segmentation, without the use of extra data.     

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study

BackgroundTo assess the impact of diabetes on restrictive and obstructive lung function impairment.MethodsThis 5-year prospective study included 7524 participants aged 40–69 years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl), HbA1c ≥ 6.5% (48 mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) < 80% predicted and forced expiratory volume in 1 s (FEV₁) to FVC ratio (FEV₁/FVC) < 0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014.ResultsDuring the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04–2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72–1.21)].ConclusionDiabetes was associated with restrictive lung function impairment but not obstructive lung function impairment.     

Wart with Depigmented Halo and Generalized Vitiligo

Depigmented haloes sometimes appear around melanocytic tumors or non-melanocytic tumors, but coexistence of warts and depigmented haloes is extremely rare. We report here an unusual case of warts accompanied by depigmented haloes and subsequently-triggered generalized vitiligo. A 55-year-old Japanese man presented with a 3-year history of brown nodules on the back, upper eyelid and dorsum of the left hand. Depigmented haloes appeared around the noldules and then gradually spread over a wide area, resulting in the development of generalized vitiligo. He had no history of antecedent treatment for these lesions before consultation. Histopathologically, the lesion showed papillomatosis and hyperkeratosis with lymphocytic exocytosis into the epidermis, which compatible to warts. Based on these clinical and histopathologic findings, a diagnosis of warts with depigmented halo and subsequently-triggered generalized vitiligo was made. None of the warts had resolved spontaneously after the appearance of haloes, and the depigmented haloes and generalized vitiligo remain unchanged.