Search

Abstract Background Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC. Methods A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time. Results The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA. Conclusions This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.

DOI: 10.3969/j.issn.1672-6731.2016.09.012

Objective To explore the value of detecting early secretory antigenic target-6 (ESAT-6) in cerebrospinal fluid (CSF) monocytes by laser scanning confocal microscopy (LSCM) techniques in early diagnosis of tuberculous meningitis (TBM), and to find a more specific method for early diagnosis. Methods Double immunofluorescence staining was applied to detect ESAT-6, and LSCM was used to observe the dyeing result of CSF monocytes and to analyze three-dimensional images. ESAT-6 positive cells will present red fluorescence cytoplasm and blue fluorescence nuclei, and negative cells present blue fluorescence nuclei while the cytoplasm is not stained. Results ESAT-6 was mainly expressed with red fluorescence in cytoplasm of CSF monocytes in patients with TBM. Among 35 cases of TBM patients, there were 28 patients (80%) ESAT-6 positive, one case (2.86%) ESAT-6 positive in the control group, and the difference was statistically significant (χ2 = 42.918, P = 0.000). ESAT-6 sensitivity was 80% and specificity was 97.14%. Conclusions The detection of ESAT-6 can provide a certain basis for the early diagnosis of TBM and has high specificity. LSCM techniques can realize simultaneously the observation of multiple fluorescence and provide clear tomography and three-dimensional images. The cytological research has been improved to a new level. DOI: 10.3969/j.issn.1672-6731.2016.08.010

Mycobacterium tuberculosis can attack many systems of people, such as central nervous system, respiratory system, urinary system, and so on. The fatality rate and disability rate of diseases caused by Mycobacterium tuberculosis are high and are rising in many areas of the world. Because of drug resistance, the diagnosis and therapy become harder. Consequently, it is of great importance for us to understand drug resistance mechanism and make an effective therapeutic schedule, so that we can timely diagnose, effectively treat and improve outcomes. This article summarizes drug resistance mechanism of Mycobacterium tuberculosis against common anti-tuberculosis drugs and its therapeutic schedule. doi: 10.3969/j.issn.1672-6731.2014.08.005

The herbicide fomesafen has the advantages of low toxicity and high selectivity, and the target of this compound is protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4). However, this herbicide has a long residual period and can have phytotoxic effects on succeeding crops. To protect maize from fomesafen, a series of thiazole phenoxypyridines were designed based on structure−activity relationships, active substructure combinations, and bioisosterism. Bioassays showed that thiazole phenoxypyridines could improve maize tolerance under fomesafen toxicity stress to varying degrees at a dose of 10 mg·kg−1. Compound 4i exhibited the best effects. After being treated by compound 4i, average recovery rates of growth index exceeded 72%, glutathione content markedly increased by 167% and glutathione S-transferase activity was almost 163% of fomesafen-treated group. More importantly, after being treated by compound 4i, the activity of PPO, the main target enzyme of fomesafen, recovered to 93% of the control level. The molecular docking result exhibited that the compound 4i could compete with fomesafen to bind with the herbicide target enzyme, which consequently attained the herbicide detoxification. The present work suggests that compound 4i could be developed as a potential safener to protect maize from fomesafen.

Cryptococcus neoformans is a kind of encapsulated fungal organism that widely exists in the nature. Because of its neurotropic nature, the central nervous system becomes its major target organ. Cryptococcus neoformans can use "transcellular pathway", "paracellular pathway" and "Trojan horse approach" to cross blood-brain barrier, and then make the devastating diffusion. Despite antifungal therapy, the mortality rate remains between 10% and 25% in patients with cryptococcal meningitis (CM) and acquired immunodeficiency syndrome (AIDS), and at least one⁃third of patients have experienced failure of antifungal therapy. Consequently, it is very important for us to understand the pathogenesis of CM, to diagnose as soon as possible and to explore more reasonable treatment.

A series of novel methyl (R)-N-benzoyl/dichloroacetyl-thiazolidine-4-carboxylates were designed by active substructure combination. The title compounds were synthesized using a one-pot route from l-cysteine methyl ester hydrochloride, acyl chloride, and ketones. All compounds were characterized by IR, 1H NMR, 13C NMR, and HRMS. The structure of 4q was determined by X-ray crystallography. The biological tests showed that the title compounds protected maize from chlorimuron-ethyl injury to some extent. The ALS activity assay showed that the title compounds increased the ALS activity of maize inhibited by chlorimuron-ethyl. Molecular docking modeling demonstrated that Compound 4e competed against chlorimuron-ethyl to combine with the herbicide target enzyme active site, causing the herbicide to be ineffective.

Spontaneous intracranial hypotension (SIH) may lead to cerebral venous thrombosis (CVT). This case report describes the diagnostic and treatment processes used for a patient with CVT caused by SIH due to spontaneous spinal cerebrospinal fluid (CSF) leakage in the high cervical region. Clinical data were collected from a 37-year-old man with an initial symptom of spontaneous posterior cervical pain. The diagnostic and treatment processes of SIH-induced CVT were described. A magnetic resonance imaging (MRI) study showed superior sagittal sinus thrombosis, and a lumbar puncture revealed a low initial CSF pressure of less than 60 mmH2O. The patient underwent anticoagulation and fluid rehydration therapies. No abnormalities were observed in the thoracic MRI scan, but a cervical MRI scan revealed a spontaneous CSF leak. An epidural blood patch with autologous blood was performed, and symptoms completely resolved 3 days after the procedure. This report proposes a diagnostic procedure for detecting rare cases of SIH-induced CVT, thereby preventing future misdiagnoses and delayed treatment. When a patient presenting with CVT in conjunction with intracranial hypotension has no history of trauma or piercing, SIH caused by spontaneous spinal CSF leakage should be considered as a potential cause of secondary low intracranial pressure. For detection of CSF leaks at rare sites, an MRI of the whole spine rather than a localized MRI of the spine needs to be performed to avoid misdiagnosis. An epidural blood patch should be performed as soon as possible as it may shorten the length of hospitalization and improve prognosis.

C17H20ClNO3S, orthorhombic, P212121 (no. 19), a = 6.1984(2) Å, b = 14.3940(5) Å, c = 18.9651(6) Å, V = 1692.06(10) ų, Z = 4, Rgt(F) = 0.0263, wRref(F²) = 0.0683, T = 293(2) K. [ABSTRACT FROM AUTHOR]

Abstract Background This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM). Methods A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software. Results The most common mutated gene was TP53 (54/62; 87.10%), followed by EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway. Conclusions This study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.