血清维生素D水平与儿童特应性皮炎的相关性分析

目的研究儿童血清中维生素D与特应性皮炎(AD)积分指数评分(SCORAD)之间的关系,同时分析血常规的嗜酸粒细胞百分比及嗜酸粒细胞绝对值、血清总IgE、血清钙离子及身高、体质量、身体质量指数与SCORAD之间的关系。方法选取2016年6月—2016年12月于我院诊治的44例AD患儿的临床资料作为观察组,并收集同时期相同数量健康儿童的资料作为对照组。观察组用SCORAD进行评分,观察组及对照组均测定其血常规、血清总IgE、血清钙离子和血清维生素D,并根据体质量、身高计算出身体质量指数(BMI),由同1名医师对患儿进行SCORAD计算。结果观察组中血清维生素D与SCORAD呈负相关(r=-0.305,P=0.044),与钙离子浓度呈正相关(r=0.366,P=0.015)。另外,SCORAD与嗜酸粒细胞百分比、绝对值及总IgE值呈正相关(r1=0.355,r2=0.398,r3=0.397;P1=0.018,P2=0.008,P3=0.008)。观察组的25(OH)D浓度低于对照组(Z=-2.028,P=0.043),嗜酸粒细胞百分比及绝对值、总IgE和钙离子浓度高于对照组(Z1=-3.965,Z2=-4.112,Z3=-2.479;P1<0.001,P2<0.001,P3=0.013)。结论儿童25(OH)维生素D可能与SCORAD有负相关。     

Exendin-4 attenuates pain-induced cognitive impairment by alleviating hippocampal neuroinflammation in a rat model of spinal nerve ligation

Glucagon-like peptide-1 receptor has anti-apoptotic,anti-inflammatory,and neuroprotective effects.It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses;however,it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms.We explored the effects of glucagon-like peptide-1 receptor on nociception,cognition,and neuroinflammation in chronic pain.A rat model of chronic pain was established using left L5 spinal nerve ligation.The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation.Electrophysiological examinations showed that,after treatment with exendin-4,paw withdrawal frequency of the left limb was significantly reduced,and pain was relieved.In addition,in the Morris water maze test,escape latency increased and the time to reach the platform decreased following exendin-4 treatment.Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus,as well as an increase in the expression of tumor necrosis factor alpha,interleukin 1 beta,and interleukin 6.All of these effects could be reversed by exendin-4 treatment.These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China(approval No.WDRM 20171214)on September 22,2017.     

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.     

Larger regional volume of the thalamus in diarrhea-predominant irritable bowel syndrome: a cross-sectional study

Brain Imaging and Behavior - As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction...     

Depletion of microglia in developing cortical circuits reveals its critical role in glutamatergic synapse development,functional connectivity,and critical period plasticity

Microglia populate the early developing brain and mediate pruning of the central synapses. Yet, little is known on their functional significance in shaping the developing cortical circuits. We hypothesize that the developing cortical circuits require microglia for proper circuit maturation and connectivity, and as such, ablation of microglia during the cortical critical period may result in a long-lasting circuit abnormality. We administered PLX3397, a colony-stimulating factor 1 receptor inhibitor, to mice starting at postnatal day 14 and through P28, which depletes >75% of microglia in the visual cortex (VC). This treatment largely covers the critical period (P19-32) of VC maturation and plasticity. Patch clamp recording in VC layer 2/3 (L2/3) and L5 neurons revealed increased mEPSC frequency and reduced amplitude, and decreased AMPA/NMDA current ratio, indicative of altered synapse maturation. Increased spine density was observed in these neurons, potentially reflecting impaired synapse pruning. In addition, VC intracortical circuit functional connectivity, assessed by laser scanning photostimulation combined with glutamate uncaging, was dramatically altered. Using two photon longitudinal dendritic spine imaging, we confirmed that spine elimination/pruning was diminished during VC critical period when microglia were depleted. Reduced spine pruning thus may account for increased spine density and disrupted connectivity of VC circuits. Lastly, using single-unit recording combined with monocular deprivation, we found that ocular dominance plasticity in the VC was obliterated during the critical period as a result of microglia depletion. These data establish a critical role of microglia in developmental cortical synapse pruning, maturation, functional connectivity, and critical period plasticity.     

胰岛素样生长因子-1与癫痫相关性的研究进展

癫痫是神经系统常见疾病之一,癫痫发作可导致脑损伤已被动物实验和临床观察证实。 胰岛素样生长因子-1（IGF-1）是神经营养保护因子,在中枢神经系统的生长、发育、分化、损伤后修复中 起到重要作用,然而它在癫痫发作中所起的作用存在争议,现回顾目前IGF-1 与癫痫相关研究,对IGF-1 与癫痫关系进行系统综述。     

Altered resting‐state functional connectivity and effective connectivity of the habenula in irritable bowel syndrome: A cross‐sectional and machine learning study

Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain–gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting‐state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula‐left dorsolateral prefrontal cortex (dlPFC) and habenula‐periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula‐right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula‐thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = ?.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula‐dlPFC, habenula‐thalamus, and habenula‐PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.     

Nicotinamide N-methyltransferase decreases 5-fluorouracil sensitivity in human esophageal squamous cell carcinoma through metabolic reprogramming and promoting the Warburg effect

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with poor prognosis. And different individuals respond to the same drug differently. Increasing evidence has confirmed that metabolism reprogramming was involved in the drug sensitivity of tumor cells. However, the potential molecular mechanism of 5-fluorouracil (5-FU) sensitivity remains to be elucidated in ESCC cells. In this study, we found that the 5-FU sensitivity of TE1 cells was lower than that of EC1 and Eca109 cells. Gas chromatography-mass spectrometry analysis results showed that nicotinate and nicotinamide metabolism and tricarboxylic acid cycle were significantly different in these three cell lines. Nicotinamide N-methyltransferase (NNMT), a key enzyme of nicotinate and nicotinamide metabolism, was significantly higher expressed in TE1 cells than that in EC1 and Eca109 cells. Therefore, the function of NNMT on 5-FU sensitivity was analyzed in vitro and in vivo. NNMT downregulation significantly increased 5-FU sensitivity in TE1 cells. Meanwhile, the glucose consumption and lactate production were decreased, and the expression of glycolysis-related enzymes hexokinase 2, lactate dehydrogenase A, and phosphoglycerate mutase 1 were downregulated in NNMT knockdown TE1 cells. Besides, overexpression of NNMT in EC1 and Eca109 cells caused the opposite effects. Moreover, when glycolysis was inhibited by 2-deoxyglucose, the roles of NNMT on 5-FU sensitivity was weakened. In vivo experiments showed that NNMT knockdown significantly increased the sensitivity of xenografts to 5-FU and suppressed the Warburg effect. Overall, these results demonstrated that NNMT decreases 5-FU sensitivity in human ESCC cells through promoting the Warburg effect, suggesting that NNMT may contribute to predict the treatment effects of the clinical chemotherapy in ESCC.     

Epidemiological and clinical comparisons of paediatric and adult sporotrichosis in Jilin Province,China

Sporotrichosis is endemic in Jilin Province of Northeast China. While paediatric cases make a substantial contribution to the epidemiological profile of sporotrichosis, the differences in the epidemiology and clinical manifestations of sporotrichosis between paediatric and adult patients remain unclear. We retrospectively reviewed the clinical records of 2968 cases of sporotrichosis (2113 adult patients aged ≥ 15 years and 855 paediatric patients aged < 15 years) over a nine-year period (01/01/2010-31/12/2018-). All the patients were diagnosed with sporotrichosis based on fungal culture of material from a skin lesion. In paediatric patients, the male:female ratio was 1.3:1, the incidence of sporotrichosis in the cold seasons was high (79.0%), most lesions occurred in the facial region (92.2%), and there was a preponderance of fixed cutaneous sporotrichosis (86.8%). In adult patients, the male:female ratio was 1:2.4, the incidence of sporotrichosis in the cold seasons was 66.0%, most lesions affected the extremities (48.6%) and the face (44.9%), and fixed cutaneous sporotrichosis was common (69.3%). The results indicate there were significant differences in the distribution of paediatric and adult sporotrichosis patients by sex, season with the highest occurrence of sporotrichosis, lesion sites and clinical types. Our results suggest that the epidemiology and clinical manifestations between paediatric and adult patients were different, and the route of infection of sporotrichosis in children may differ from that of adults in Jilin Province.     

ArcCHECK系统在食管癌螺旋断层放疗计划验证中的应用

目的 探讨ArcCHECK系统在食管癌断层治疗旋转照射和固定野照射计划验证中的应用,总结相关经验。方法 对32例不同部位食管癌分别制作Helical旋转照射和Direct固定野照射验证计划,并通过ArcCHECK测量、分析,对比验证结果通过率。分析靶体积与计划验证通过率的相关性。将靶体积较小的治疗验证计划分别放在ArcCHECK模体中心和外周探测点处,分析验证通过率差异。结果 Helical计划验证通过率高于Direct计划(P<0.01),其靶体积与验证通过率的相关系数分别为-0.364和-0.042,P值分别为0.041和0.819。Helical计划采用3%/2mm标准时,高剂量区放在模体中心和外周探测点处测得的通过率不同(P=0.005),后者通过率更高;采用3%/3mm标准时与Direct计划的3%/3m、3%/2mm标准的相近(P均>0.05)。结论 Helical计划验证通过率普遍高于Direct计划,原因可能与ArcCHECK探测器的角度响应以及因更多参考点受到低剂量辐射而未参与计算有关,另外还可能跟Direct计划对断层治疗剂量控制系统要求更高有关。在Helical验证计划中,当采用3%/3mm标准时,靶体积越大,验证时出现较低通过率的可能性增加,但相关系数较低。验证计划的高剂量区位于模体中心或者探测点处都可以实现计划验证,综合考量建议放在模体等中心处。