Cerebral venous thrombosis presented with symmetrical crescent-shaped intracranial hemorrhage in alcoholic liver disease: Case reports.

RATIONALE: Cerebral venous thrombosis (CVT) is a relatively uncommon but fatal disease. It can be caused by a variety of hereditary or acquired thrombotic diseases. Initial presentation with intracranial hemorrhage (ICH) in CVT is rare but can further complicate the therapeutic measures and prognosis. Cases of CVT presented with ICH in patients with alcoholic liver disease (ALD) have not been described in the literature, and it might be related with hemostatic abnormalities in ALD patients. PATIENT CONCERNS: We report 2 cases of men admitted to our hospital who were diagnosed with CVT but initially presented with symmetrical crescent-shaped ICH; both of them were ALD patients. DIAGNOSES: Cerebral imaging revealed extended CVT in both cases. The first case was a 64-year-old man with ALD deteriorated with unconsciousness and convulsions; computed tomography showed symmetrical crescent-shaped ICH in the right temporal lobe, and magnetic resonance venography revealed CVT. Another 50-year-old man with ALD complained about dizziness and weakness of his right limbs; computed tomography revealed symmetrical crescent-shaped ICH in bilateral parietal and occipital lobes, and magnetic resonance venography revealed CVT. INTERVENTIONS: The first patient was referred to the endovascular thrombectomy. Both of them were treated with anticoagulation treatment. OUTCOMES: Favorable outcomes were observed in both patients. LESSONS: Symmetrical or multiple crescent-shaped ICH requires a high suspicion in the diagnosis of CVT; even with hemorrhage, it is still important to initiate anticoagulation therapy promptly. The crescent-shaped ICH might be a new sign for CVT, and further studies are needed in the underlying mechanisms of ALD and potential thrombophilia.

Inflammatory myofibroblastic tumor of the upper arm: A case report.

RATIONALE: Inflammatory myofibroblastic tumor (IMT) is an uncommon benign myofibroblastic tumor that usually occurs in the lung, mediastinum, abdomen and vulvovaginal region. IMT of the upper arm is exceedingly rare with unknown etiology. Pathology plays a major role in the diagnosis of IMT, and radiological characteristics of the condition are crucial for differential diagnosis. PATIENT CONCERNS: A 62-year-old woman was admitted to our hospital for a complaint of a mass in her left upper limb with progressive numbness in the extremity. Ultrasound examination of the brachial artery (BA) revealed a hypoechoic mass with well-defined borders and a substantial blood flow, and the mass was also shown to be greatly enhanced on computed tomography (CT) and magnetic resonance imaging (MRI). DIAGNOSIS: The subsequent histopathological and immunohistochemical studies led to the diagnosis of IMT. INTERVENTION: The patient was referred for surgery. The soft tissue tumor resection, left median nerve release operation, brachial artery vascular grafting, and arterial anastomosis were performed. OUTCOME: Favorable outcome was observed. The patient recovered well from the procedure and did not experience any further complications or tumor recurrence. LESSONS: In this report, we describe a case of IMT of the upper arm with BA involvement. The case expands the differential diagnosis of limb neoplasm and broadens the understanding of its ultrasonic and radiological imaging features. It also serves as a further example of an uncommon region distinct from conventional IMT. Further studies on the etiology and therapeutic strategies are needed.

Electrochromatographic behavior of core-shell particles: A comparison study.

Core-shell particle is a new generation high performance packing material for liquid chromatography. Through comparison with a classical totally porous silica phase of the same particle size, we studied Ascentis Express 5 µm core-shell particle's electrochromatographic behavior, in terms of voltage-current property, electroosmotic flow (EOF) and van Deemter curve. It was found, due to the nonpermeable solid core, the core-shell particle presented a diminished EOF and efficiency than the totally porous paricle. This on the other hand proved that the intra-particle pore flow extensively exists and plays an important role in electrochromatography on totally porous material. The core-shell particle's high retentivity led to an enhanced resolution for weakly retained hydrophilic peptides, which were poorly retained and co-eluted on totally porous particles. Further exploration has shown the core-shell material can achieve efficient electrochromatography of protein digests, excellent performance in terms of resolution, reproducibility and long term stability have been observed. The results indicate that the core-shell structure may suggest a reasonable design of stationary phase for bioelectrochromatography of peptides and proteins.

Genetic analysis of ATP13A2, PLA2G6 and FBXO7 in a cohort of Chinese patients with early-onset Parkinson's disease.

Several genes have already been certified as causative genes in patients with autosomal recessive early-onset Parkinson's syndrome with pyramidal tract signs, including ATP13A2, PLA2G6 and FBXO7. Variants in these three genes may also play roles in early-onset Parkinson's disease (EOPD). In order to investigate the contribution of genetic variants in these three genes to Chinese sporadic EOPD patients, we screened 101 Chinese sporadic EOPD patients and 83 age- and sex-matched healthy controls using direct sequencing. Interpretation of those detected variants was performed based on the guidelines developed by the American College of Medical Genetics and Genomics (ACMG). Two missense variants, p.G360E and p.T733M, with "uncertain significance" classification were identified in the ATP13A2 gene and five synonymous variants were significantly over-represented in EOPD patients. Two missense variants, p.R53C and p.T319M, were absent in both our control group and online databases, classified as "likely pathogenic" in the PLA2G6 gene. Only benign variants were identified in the FBXO7 gene. These results indicate that rare variants of PLA2G6 may contribute to PD susceptibility in Chinese population, the ATP13A2 might be associated with higher risk for sporadic EOPD, while the FBXO7 gene doesn't seem to be a risk factor to develop sporadic PD in Chinese population. Further biochemical and molecular biological studies needs to be conducted to support our main results in our future researches.

Genetic Analysis of PICK1 Gene in Alzheimer's Disease: A Study for Finding a New Gene Target.

Background: Alzheimer's disease (AD) is a neurodegenerative disease with no effective treatment. Researchers have focused on exploring biomarkers for its early diagnosis, especially on finding a new gene target. Recent studies have shown that protein interacting with C-kinase-1(PICK1) is related to AD through regulating hippocampal synaptic plasticity. PICK1 gene polymorphisms have been identified in psychological and other related disorders. Methods: This study included 133 sporadic AD patients and 173 healthy controls. All coding exons and intron-exon boundaries of the PICK1 gene were amplified by polymerase chain reaction (PCR), which were subsequently sequenced and analyzed. Results: This is the first genetic association study to investigate the association between PICK1 gene and AD risk in Chinese Han population. Seven single nucleotide polymorphisms (SNPs) were found in our research (rs397780637, rs713729, rs2076369, rs58230476, rs7289911, rs149474436; and rs146770324 for patient M1659 only). Frequencies of the T allele (p = 0.002; OR, 0.083; 95%CI, 0.011-0.634) and TT/TC genotypes (p = 0.001) of rs149474436 were lower in AD patients than in the controls. The GG homozygotes of rs397780637 were found to be associated with an increased risk of AD (p = 0.018) in APOEε4 allele carriers, while the frequency of the T allele of rs149474436 was significantly lower among AD patients in APOEε4 non-carriers (p = 0.005). Conclusions: Our results suggest that PICK1 gene SNPs are associated with AD susceptibility in East Asian population, T allele of rs149474436 may play as a protective factor while the rs397780637 GG homozygotes may be associated with an increased risk of AD. Further studies should be considered in a larger cohort of patients with diverse demographics.

Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene.

It has been reported that FERM domain containing 7 (FRMD7) may cause X-linked idiopathic congenital nystagmus (ICN). A total of >40 mutations of the FRMD7 gene have been identified, however their pathogenic role remains unclear. In the present study, enhanced green fluorescent protein-tagged wild-type (WT) and mutant (MT) FRMD7 (c. C781>G) were expressed in stably expressing human neuroblastoma SH-SY5Y cells following viral transfection and antibiotic selection. Uniform expression of the FRMD7 fusion proteins was confirmed via fluorescence microscopy and western blotting. The expression profiles of neuron-specific proteins and Rho guanine triphosphatases (GTPases) differed significantly between the wild-type and mutant cell lines. Levels of Mtap2, NF-M, nestin, GAP43 and Rac1 mRNA were significantly increased in MT-FRMD7 cells compared with controls (P<0.01). However, the expression of Rac1 protein did not differ significantly among the two cell lines. Taken together, the results of the current study suggest that MT-FRMD7 influences the expression of neuron-specific genes and Rho GTPases, which may be involved in the pathogenesis of ICN. The FRMD7 stable expression cell line may facilitate future studies investigating the role of this protein in neuronal development.

The Relationship between Parkinson Disease and Brain Tumor: A Meta-Analysis.

OBJECTIVE: Epidemiological studies have investigated the association between Parkinson disease (PD) occurrence and the risk of brain tumors, while the results remain controversial. We performed a meta-analysis to clarify the exact relationship between PD and brain tumors. METHODS: A systematic literature search was conducted using PubMed, Embase, ScienceDirect and CBM (China Biology Medicine Disc) before February 2016. Eligible studies were those that reported risk estimates of brain tumors among patients with PD or vice versa. A random-effects model was used to calculate the pooled odds ratio (OR) of the outcomes. Subgroup analyses and sensitivity analysis were conducted to explore the potential sources of heterogeneity. RESULTS: In total, eight studies involving 329,276 participants met our inclusion criteria. The pooled OR was 1.51 (95%CI 1.21-1.89), indicating that PD carried a higher risk of brain tumor. Analyses by temporal relationship found that the occurrence of brain tumor was significantly higher after the diagnosis of PD (OR 1.55, 95% CI 1.18-2.05), but not statistically significant before PD diagnosis (OR 1.21, 95%CI 0.93-1.58). Subgroup analysis showed that gender differences, ethnicity differences and the characteristic of the tumor (benign or malignant) did not make much change in the association between brain tumor and PD. CONCLUSIONS: Our meta-analysis collecting epidemiological studies suggested a positive association of PD with brain tumors, while the influence of anti-parkinson drugs and ascertainment bias could not be excluded. Further studies with larger sample size and more strict inclusion criteria should be conducted in the future.

Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application.

Parkinson's disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of the α-synuclein protein (encoded by the SNCA gene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson's disease. The SNCA gene has undergone gene duplications, triplications, and point mutations. However, the specific mechanism of α-synuclein in Parkinson's disease remains obscure. Recent research showed that various α-synuclein oligomers, pathological aggregation, and propagation appear to be harmful in certain areas in Parkinson's disease patients. This review summarizes our current knowledge of the pathogenetic dysfunction of α-synuclein associated with Parkinson's disease and highlights current approaches that seek to develop this protein as a possible diagnostic biomarker and therapeutic target.

Intracranial hypertension as the primary symptom of gastric signet-ring cell carcinoma: A case report and literature review.

BACKGROUND: Intracranial hypertension (IH) is a neurological disorder characterized by increased intracranial pressure. It is a poorly understood syndrome that most commonly manifests nonspecific symptoms such as stroke-like headache, vision changes, nausea, vomiting, and papilledema. IH has been reported in young cancer patients but never in association with gastric signet-ring cell carcinoma. METHODS: Here, we discuss the case of an 18-year-old girl with gastric signet-ring cell carcinoma in which IH was the primary symptom accompanied by the even rarer symptom of cutaneous metastases. We also present a review of the relevant literature. The patient experienced frequent headaches, vomiting, and blurred vision but showed no abnormal findings on cranial imaging studies. Further examination showed multiple skin nodules on the abdomen. Then pathological and immunohistochemical examination of gastroscopic specimens and the biopsied subcutaneous nodules were done. RESULTS: Pathological and immunohistochemical examination of gastroscopic specimens and the biopsied subcutaneous nodules confirmed gastric signet-ring cell carcinoma with skin metastases. CONCLUSION: To our knowledge, this is the first reported case of gastric signet-ring cell carcinoma primarily presenting IH and accompanied by subcutaneous metastases. This case emphasizes the importance of excluding malignancy from the differential diagnosis of IH.

Two dimensional separations of human urinary protein digest using a droplet-interfaced platform.

For highly complex mixtures, coelution is a common phenomenon in chromatography. A great deal of resolution is hidden in coelution, and lost due to inevitable molecular diffusion during sample transfer. The molecular diffusion may lead to band broadening and remix of separated peaks, which cause degradation of achievable resolution. In this study, we introduced droplet microfluidics as a high performance sample transfer tool in two dimensional nanoflow liquid chromatography-capillary electrophoresis separation of a human urine sample. The fine fractionation capability and sampling completeness enabled by the droplet-interface demonstrated the 2D system's usefulness in high-resolution mapping of real world biological samples.

Towards high peak capacity separations in normal pressure nanoflow liquid chromatography using meter long packed capillary columns.

Single shot proteomics is a promising approach to high throughput proteomics analysis. In this strategy, long capillary columns are needed to perform long and shallow gradients to achieve high peak capacity and good peak width for informative mass spectrometric detection. Herein, we report that meter long capillary columns, packed with 5 µm particulate material, can be facilely fabricated based on single particle fritting technology. The long columns could reliably generate high peak capacities of 800 in 10 h long gradients for protein digest separations. The operation was within the pressure range (40 MPa) of the most widely used normal pressure nanoLC systems. Due to the excellent life time (>100 injections) and inter-column performance consistency, the meter long capillary columns reported here should be of practical usefulness in single shot proteomics without the need for ultra-high pressure instrumentation.

A comparison study of in-column and on-column detection for electrochromatography.

Duplex capillary columns, the standard for electrochromatography using optical detection, consist of a packed and an open section. Normally, optical detection is performed in an on-column manner, i.e. at a point right after the packed section. It was deemed that band broadening may take place when an analyte band travels from the packed bed, through the frit and down to the open section. In this study, without using any sintering steps for fritting or window creation, robust packed capillary columns were prepared using transparent capillaries based on single particle fritting technology. The detection point could be easily shifted by simply sliding the transparent column against the ultraviolet (UV) beam. In this way, the band broadening effect was directly evaluated as a function of the detection point, which was positioned before or after the end frit. The consistent van Deemter curves recorded indicate that there was no efficiency difference between the positions investigated. The result proved that the significant band broadening effect previously observed via on-column detection should be caused by the sintered frit used, while the single particle frit made through a purely physical process did not lead to efficiency degradation. The conservative separation performance recorded at different positions around the column's end also suggests the applicability of on-line tandem detection strategy, e.g. UV followed by mass spectrometry (MS), on the same capillary column, which should be a promising approach to mining multiplex detection information from a single microseparation process.

A multiplexed nucleic acid microsystem for point-of-care detection of HIV co-infection with MTB and PCP.

Many individuals infected with the human immunodeficiency virus (HIV), especially children in African countries, die of co-infections with Mycobacterium tuberculosis (MTB) (coinfection rate: 50%) or Pneumocystis carinii pneumonia (PCP) (coinfection rate: 81%). The present proposal describes a rapid, portable, low-cost, multiplexed point-of-care diagnostic technique for simultaneously detecting HIV, MTB, and PCP. This technique incorporates a creative micro-device (hardware) and a loop-mediated isothermal amplification strategy (software).

Quantitative research of histone H3 acetylation levels of human hepatocellular carcinoma cells.

BACKGROUND: Core histone H3 is a highly conserved protein in the cell nucleus, it goes through various post-translational modifications easily, and the state of the acetylation has clinical diagnostic significance in prostate cancer, breast cancer, lung cancer and other diseases. RESULTS: In this work, the combinatorial method of chromatographic separation, methylation isotope labeling and LTQ-Orbitrap(®) MS was employed to quantify the acetylation sites of histone H3 separately within normal liver cells L02 and hepatocellular carcinoma (HCC) cells HepG2, HCC metastasis cells 97H and HCC cells HepG2, high HCC metastasis potential cells LM3 and low HCC metastasis potential cells 97L. In comparison with the quantitative results of HepG2 and L02, the amounts of five acetylated and methylated peptides were found decreased. Similarly, when comparing the 97H with HepG2, the amounts of eight acetylated and methylated peptides were found decreased, and when comparing the LM3 with 97L, the amounts of six acetylated and methylated peptides were found decreased. CONCLUSION: These results provide some fundamental reference information for the research into post-translational modifications of histones in human liver cancer and other related diseases.

A portable and integrated nucleic acid amplification microfluidic chip for identifying bacteria.

In this work, we developed a portable integrated microchip of loop-mediated isothermal nucleic acid amplification (LAMP). This chip, with sample-to-answer capability, could perform rapid DNA release, exponential signal amplification and naked-eye result read-out in single or multiplex format. We call it iµLAMP, namely integrated micro-LAMP, which was successfully used for point-of-care identification of bacteria.

Characterization of diverse non-covalent interactions associated with protein acetylation.

Protein acetylation has early emerged as a major posttranslational modification for histones and was recently found to be involved in a variety of biological events such as enzymatic activation and signal transduction. Traditional notion about the physicochemical effects associated with protein acetylation is mainly because of its presence capable of neutralizing positively charged protein system, while diverse non-covalent interactions arising from the acetylation are largely ignored and have never been investigated systematically. In the current work, we perform a comprehensive examination of the geometrical profile and energetic landscape of such acetylation-related non-covalent interactions in protein context by using a combination of high-level ab initio calculations, crystal structure survey, and hybrid mechanical/molecular mechanical analysis, on the basis of small model complexes and real protein systems. It is all coming together to suggest that the formation of complicated non-covalent networks around the acetylated site of protein is fundamentally important for stabilizing local structure, improving systemic rigidity, and even conducting more sophisticated biological functions such as switching enzymatic activity.