参附注射液治疗老年重症肺炎的疗效研究

目的探讨参附注射液对老年重症肺炎疗效及N末端B型利钠肽原(NT-pro BNP)的影响。方法选择2016年6月—2019年6月医院收治的老年重症肺炎患者80例,以随机数表法将其分为两组,即对照组与研究组各40例。对照组患者接受常规对症治疗,研究组在此基础上应用参附注射液治疗。对比两组临床疗效,治疗前与治疗3 d、5 d时血浆NT-pro BNP水平,以及不良反应情况。结果研究组治疗的总有效率为95.00%,高于对照组77.50%(P<0.05)。治疗后3 d与5 d时研究组血浆NT-pro BNP水平均低于对照组(P<0.01)。两组治疗期间均未见明显的药物不良反应。结论参附注射液能够有效提高老年重症肺炎患者的疗效,调节脑钠肽水平。     

(Re)organisation of the somatosensory system after early brain lesion: A lateralization index fMRI study

ObjectiveTo evaluate the relationship between neural (re)organization of the somatosensory cortex and impairment of sensory function (2-point discrimination [2PD]) in individuals with unilateral cerebral palsy.MethodsWe included 21 individuals with unilateral cerebral palsy. 2PD thresholds were evaluated on thumb pads, and activation of the somatosensory cortex was recorded by functional MRI (fMRI) during passive movements of the affected hand. A lateralization index (LI) was calculated for the primary sensory (S1) and secondary sensory (S2) cortices and the correlation between the LI and 2PD thresholds was analysed.ResultsWe found a significant negative correlation between the 2PD thresholds and the S2 LI (r = −0.5, one-tailed P-value = 0.01) and a trend towards a negative correlation with the S1 LI (r = −0.4, one-tailed P-value = 0.05).ConclusionHigh levels of activation in the contralesional hemisphere were associated with high levels of sensory impairment in individuals with unilateral cerebral palsy. The interhemispheric (re)organization of the somatosensory system may not effectively compensate for somatosensory impairment.     

Pharmacokinetics and brain penetration study of chlorogenic acid in rats

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with t_max of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC_0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC_{brain, IN}) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC_{brain, IV}) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.     

Variables associated with subjective cognitive change among Iraq and Afghanistan war Veterans with blast-related mild traumatic brain injury

Introduction: This study investigated variables associated with subjective decline in executive function among Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) following a history of blast-related mild traumatic brain injury (mTBI).

Method: Fifty-six male U.S. Veterans (M_Age = 35.3 ± 8.8 years) with a history of blast-related mTBI (6.6 ± 3.2 years post injury) completed a battery of self-report questionnaires and neuropsychological measures. Participants rated current and retrospectively estimated pre-mTBI executive function difficulties on the Frontal Systems Behavior Scale (FrSBe). A difference score (post- minus pre-mTBI ratings) was the dependent variable (?FrSBe). Linear regression models examined variables predicting ?FrSBe, including: pre-injury characteristics (education, premorbid intelligence), injury-related characteristics (number of blast exposures, losses of consciousness), post-injury clinical symptoms (PTSD Checklist–Military version; Pittsburgh Sleep Quality Index), and post-injury neuropsychological performances on executive function measures (Trail Making Test Part B; Controlled Oral Word Association Test; Auditory Consonant Trigrams; Wisconsin Card Sorting Test).

Results: While 11% of participants had a clinically elevated pre-injury FrSBe total score, 82% had a clinically elevated post-injury FrSBe total score. Only self-reported PTSD symptom severity independently predicted perceived change in executive function.

Conclusions: Many OEF/OIF/OND Veterans with a history of blast-related mTBI experience subjective decline in executive function following injury. Perceived executive function decline was associated with higher PTSD symptom severity, aligning with previous research associating PTSD with cognitive complaints. Results did not support a correspondence between perceived cognitive change and neuropsychological performances.     

Effect of interictal epileptiform discharges on EEG-based functional connectivity networks

ObjectiveFunctional connectivity networks (FCNs) based on interictal electroencephalography (EEG) can identify pathological brain networks associated with epilepsy. FCNs are altered by interictal epileptiform discharges (IEDs), but it is unknown whether this is due to the morphology of the IED or the underlying pathological activity. Therefore, we characterized the impact of IEDs on the FCN through simulations and EEG analysis.MethodsWe introduced simulated IEDs to sleep EEG recordings of eight healthy controls and analyzed the effect of IED amplitude and rate on the FCN. We then generated FCNs based on epochs with and without IEDs and compared them to the analogous FCNs from eight subjects with infantile spasms (IS), based on 1340 visually marked IEDs. Differences in network structure and strength were assessed.ResultsIEDs in IS subjects caused increased connectivity strength but no change in network structure. In controls, simulated IEDs with physiological amplitudes and rates did not alter network strength or structure.ConclusionsIncreases in connectivity strength in IS subjects are not artifacts caused by the interictal spike waveform and may be related to the underlying pathophysiology of IS.SignificanceDynamic changes in EEG-based FCNs during IEDs may be valuable for identification of pathological networks associated with epilepsy.     

基于机器学习的脑胶质瘤多模态影像分析

脑部胶质瘤是临床中常见的一种原发性脑肿瘤，具有复发率高、死亡率高以及治愈率低的特点。常规临床诊断主要依靠计算机断层扫描(CT)和磁共振成像(MRI)检查技术进行鉴别。随着成像技术和机器学习方法的不断发展，多模态影像智能分析技术已经逐步成为研究热点，在脑胶质瘤的病灶分割测量、肿瘤分级、预后生存周期预测和基因型辨别等方面具有重要的应用前景。本文重点介绍基于机器学习和多模态影像在脑胶质瘤临床辅助诊断和预后评估中的应用进展。     

Variaciones de los plexos coroideos y las barreras cerebrales en la hipertensión arterial y el envejecimiento

IntroductionThe choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers.DevelopmentThe choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood–CSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved.ConclusionsHBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100β and TTRm levels.     

Vasoactive Intestinal Peptide Immunoregulatory Role at the Periapex: Associative and Mechanistic Evidences from Human and Experimental Periapical Lesions

IntroductionThe balance between the host proinflammatory immune response and the counteracting anti-inflammatory and reparative responses supposedly determine the outcome of periapical lesions. In this scenario, the vasoactive intestinal peptide (VIP) may exert a protective role because of its prominent immunoregulatory capacity. In this study, we investigated (in a cause-and-effect manner) the potential involvement of VIP in the development of human and experimental periapical lesions.MethodsPeriapical granulomas (n = 124) and control samples (n = 48) were comparatively assessed for VIP and multiple immunologic/activity marker expression through real-time polymerase chain reaction. Experimental periapical lesions (C57Bl/6 wild-type mice) were evaluated regarding endogenous VIP expression correlation with lesion development and the effect of recombinant VIP therapy in lesion outcome. CCR4KO and IL4KO strains and anti-glucocorticoid-induced TNFR-related protein inhibition were used to test the involvement of Treg and Th2 cells in VIP-mediated effects.ResultsVIP expression was more prevalent in periapical granulomas than in controls, presenting a positive association with immunoregulatory factors and an inverse association/correlation with proinflammatory mediators and the receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio. Endogenous VIP expression up-regulation was temporally associated with lesion immunoregulation and a decline of bone loss. VIP therapy in mice prompted the arrest of lesion development, being associated with an anti-inflammatory and proreparative response that limits the proinflammatory, Th1, Th17, and osteoclastogenic response in the periapex. The VIP protective effect was dependent of Treg migration and activity and independent of interleukin 4.ConclusionsOur results show that VIP overexpression in human and experimental periapical lesions is associated with lesion inactivity and that VIP therapy results in the attenuation of experimental lesion progression associated with the immunosuppressive response involving Treg cells.     

Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets

BackgroundEndovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date.ObjectiveTo establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS.MethodsNeuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed.ResultsSix out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue.ConclusionsWhile several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.