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Introduction Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).Methods and analysis The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 μs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events.Ethics and dissemination This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.Trial registration number ChiCTR2300073950.

Cellular angiolipoma is a rare subtype of angiolipoma, with vascular density approaching 95%. This case report describes a 55-year-old female that presented for treatment of a mass in her left breast that had been tender to slightly painful on palpation for nearly 2 years The patient underwent surgical excision of the mass, which was pathologically confirmed as a cellular angiolipoma. As of the 3-year follow-up, the patient reported no recurrence of the lesion. It is important to report this case and refresh knowledge of this and similar lesions to raise awareness of this diagnosis and treatment and improve future management of cellular angiolipoma cases.

Abstract Background T cell acute lymphoblastic leukemia (T-ALL) defines a group of hematological malignancies with heterogeneous aggressiveness and highly variable outcome, making therapeutic decisions a challenging task. We tried to discover new predictive model for T-ALL before treatment by using a specific pipeline designed to discover aberrantly active gene. Results The expression of 18 genes was significantly associated with shorter survival, including ACTRT2, GOT1L1, SPATA45, TOPAZ1 and ZPBP (5-GEC), which were used as a basis to design a prognostic classifier for T-ALL patients. The molecular characterization of the 5-GEC positive T-ALL unveiled specific characteristics inherent to the most aggressive T leukemic cells, including a drastic shut-down of genes located on the mitochondrial genome and an upregulation of histone genes, the latter characterizing high risk forms in adult patients. These cases fail to respond to the induction treatment, since 5-GEC either predicted positive minimal residual disease (MRD) or a short-term relapse in MRD negative patients. Conclusion Overall, our investigations led to the discovery of a homogenous group of leukemic cells with profound alterations of their biology. It also resulted in an accurate predictive tool that could significantly improve the management of T-ALL patients.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Previous studies have shown that inflammatory chemokines are involved in the physiological functions of cytoskeletal reorganization, cell migration, adhesion and immune responses. However, in the past decade, there have been studies showing that inflammatory chemokines play a key role in CVD. Importantly, CXC motif chemokine ligand 2 (CXCL2) has been shown to be involved in the pathogenesis of cardiovascular disease. CXCL2 exerts its effects on the cardiovascular system by mediating inflammatory responses, but the specific signaling pathways by which CXCL2 exerts its effects in CVD remain unknown and need to be further investigated. This review aims to investigate the expression changes of CXCL2 in acute myocardial infarction (AMI), atherosclerosis (AS), obesity, diabetes and ischemic stroke (IS) and its potential key role in cardiovascular disease in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Diabetic retinopathy(DR), one of the major complications of diabetes which can causes diabetic macular edema and visual loss. Vascular changes in DR correlate with the cellular damage and pathological changes in the capillaries of blood-retinal barrier. Several cytokines have been involved in inducing neovascularization. These cytokines activate different signaling pathways which are mainly responsible for the complications of DR. MicroRNAs(miRNAs)have been introduced as the key factors in the regulation of the cytokine expression which plays a critical role in neovascularization of retinal cells. Some studies have shown that changing levels of miRNAs have essential role in the pathophysiology of vascular changes in patients with DR. This paper reviews the role of microRNAs in the pathogenesis of DR by activating the angiogenesis pathway.

Diabetic retinopathy(DR)is the most common retinal vascular disease, seriously compromising visual function and quality-of-life. Retinal laser photocoagulation is one of the safest, most effective, and economical methods used to treat DR, but is associated with certain side-effects developing at the time of treatment. Given the continuous developments in diagnostic and treatment modalities, the complications associated with the use of traditional single-point lasers are becoming better understood. Today, the clinical demand for multi-point scanning lasers is increasing, but the effectiveness and safety of both treatments require further exploration. Here, we review the effects of laser treatment on vision, fundus fluorescein angiography, the visual field, visual function, macular edema, and the corneal nerve.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy.Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed.Results: The median DOT was 9.1 months (95% CI: 8.5–9.8), and the median OS was 26.2 months (95% CI: 24.2–28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set.Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Posterior cotical atrophy (PCA) is a kind of progressive dementia with main clinical manifestations of visual dysfunction as the starting symptom and associated with progressive cognitive disorder. The histopathology and imaging of PCA show visual dysfunction, neuritic plaques (NPs) and neurofibrillary tangles (NFTs), which are the same as those in Alzheimer's disease (AD). Researches also showed that mutation of presenilin-1 (PS-1) gene and apolipoprotein E (ApoE) genotype may participate in the occurrence and development of PCA. Parieto-occipital lobe atrophy, hypoperfusion and/or glucose metabolism reduction in the right posterior cerebrum can be seen in PCA. Cholinesterase inhibitors (ChEIs) may improve the symptoms and postpone the progression of illness. No unified diagnostic criteria will reduce the comparability between different studies. Reasonable usage of the diagnostic criteria of PCA will be helpful in classifying and differentiating this disease. DOI: 10.3969/j.issn.1672-6731.2016.06.011

Objective It is commonly known that gait disturbance is related with Alzheimer's disease (AD) in its late stage. However, recent studies showed that gait disturbance may start in the early stage of AD or even mild cognitive impairment (MCI). This paper aims to explore the correlation of gait speed and Timed Up & Go (TUG) with AD and MCI. Methods All subjects were examined by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Besides, they were designed to walk in two assigned conditions: single task (free gait) and dual task (walking and counting). The gait parameters of Four-Meter Walk Test (4mWT) and TUG were measured in the two conditions. Results Forty-two patients with AD, 39 with MCI and 39 control subjects were enrolled in this study. Compared with control group, both single and dual gait speed of MCI and AD groups decreased (MCI single: t = -3.223, P = 0.002; MCI dual: t = -2.476, P = 0.016; AD single: t = -3.793, P = 0.003; AD dual: t = -12.708, P = 0.000). For TUG, compared with control group, both single and dual tasks of MCI and AD groups increased (MCI single: t = 2.831, P = 0.006; MCI dual: t = 4.060, P = 0.000; AD single: t = 3.420, P = 0.001; AD dual: t = 4.259, P = 0.000). As for the comparison between MCI and AD groups, dual gait speed of AD group decreased (t = -8.254, P = 0.000), but there was no significant increase of both single and dual TUG in AD group (single: t = 1.569, P = 0.121; dual: t = 1.904, P = 0.061). Compared with single task, no significant difference existed in dual gait speed of MCI group (t = -1.934, P = 0.057), while dual TUG of MCI group increased (t = 3.693, P = 0.000); dual gait speed of AD group decreased (t = -12.333, P = 0.000), while dual TUG increased significantly (t = 2.584, P = 0.012). Conclusions Gait disturbance can be found even in early stage of dementia, so gait speed and TUG are reliable parameters for identification of AD, even MCI. Dual TUG increasing is meaningful for both AD and MCI, while dual gait speed shows its great significance in AD. DOI: 10.3969/j.issn.1672-6731.2015.07.011

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General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofo-linduced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness. [ABSTRACT FROM AUTHOR]