Diagnosis, treatment and genetic analysis of a case of familial aldosteronism type II with WFS1 gene mutation.

Primary aldosteronism (PA) is a disease characterized by hypertension and hypokalemia due to the excessive aldosterone secretion from the adrenal cortex, which leads to the retention of both water and sodium, and the inhibition of the renin-angiotensin system as well. Familial hyperaldosteronism type II (FH-II) is known as an autosomal dominant hereditary disease, which is a scarce cause of PA. In this report, we cllected the clinical data of a patient with repeated hypertension and hypokalemia of uncertain diagnosis since 2014. Nevertheless, we discovered by genetic sequencing in 2021 that the CLCN2 and WFS1 gene mutation of the patient, whose mother belongs to heterozygote genotype and father belongs to wild-type genotype. Combined with a series of endocrine function tests and imaging studies, the patient was finally certified her suffering from FH-II and WFS1 gene mutation. By summarizing and analyzing the characteristics and genetic test results of this case, we recommended gene sequencing for patients with PA whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.

Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing.

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.

Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis.

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.

Cerebral venous thrombosis caused by spontaneous intracranial hypotension due to spontaneous spinal cerebrospinal fluid leakage in the high cervical region: a case report.

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.

High electrochemical performance carbon nanofibers with hierarchical structure derived from metal-organic framework with natural eggshell membranes.

Carbon nanofibers with hierarchical structure were synthesized by combining Co-containing zeolitic imidazolate frameworks (ZIF-67) with natural eggshell membranes (ESMs). Benefiting from the hierarchical structure and element modification of Co/N, the obtained nanofibers exhibited excellent oxygen reduction reaction (ORR) performance. The reusing of ESMs trash made this strategy meaningful for environment.

Aptamer-Embedded Zirconium-Based Metal-Organic Framework Composites Prepared by De Novo Bio-Inspired Approach with Enhanced Biosensing for Detecting Trace Analytes.

A series of Zr-based metal-organic framework (MOF) composites embedded with three kinds of aptamer strands (509-MOF@Apt) were achieved by a one-step de novo synthetic approach. A platform for ultrasensitive detection of analytes, namely, thrombin, kanamycin, and carcinoembryonic antigen (CEA), was also established. Considering the conformational changes caused by the binding interactions between aptamer strands and targeted molecules, the label-free electrochemical aptasensors based on 509-MOF@Apt composites could be developed to detect various target molecules. By comparing the common fabrication approaches of aptasensors, a distinct determination mechanism was presented through analysis of the electrochemical measurements on different interaction behaviors between probe aptamer strands and 509-MOF materials. The optimized aptasensors based on 509-MOFs@Apt demonstrated excellent sensitivity (with the detection limit of 0.40, 0.37, and 0.21 pg mL-1 for CEA, thrombin, and kanamycin, respectively), stability, repeatability, and applicability. This work will provide a new platform for direct and feasible detection in biosensing related to clinical diagnostics and therapeutics, and further, extend the scope of potential applications for MOF materials.

Genetic polymorphisms of CCL1 rs2072069 G/A and TLR2 rs3804099 T/C in pulmonary or meningeal tuberculosis patients.

CCL1, one of the members of the CC chemokine family, is an inflammatory mediator that stimulates the migration of human monocytes. CCL1 expression is induced by Mycobacterium tuberculosis and TLR ligands in macrophage. TLR2 plays critical role in host immune response against M. tuberculosis infection by regulating the macrophage activation and cytokine secretion. M. tuberculosis causes different clinical forms of tuberculosis (TB) disease. Single-nucleotide polymorphisms (SNPs) in the CCL1 gene and TLR2 gene may be associated with the development of different clinical forms of TB, depending on the different immune mechanisms. This study was to evaluate the possible association between CCL1 rs2072069 G/A or/and TLR2 rs3804099 T/C (T597C) polymorphisms and pulmonary tuberculosis (PTB) or/and tuberculous meningitis (TBM) in a sample of the Chinese adult population. A case-control study was designed to compare the allele frequency and genotype distribution between control (n=386) and TB (n=341) who had either PTB (n=230) or TBM (n=111). The genotype typing was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TLR2 variant genotype 597CC was associated with susceptibility to PTB rather than to TBM. In the male PTB subgroup, 597CC genotype was identified in a higher rate, compared with male control subgroup. This study demonstrates that T597C polymorphism of TLR2 is a risk factor for susceptibility to PTB rather than to TBM in a sample of Chinese adult population. Patient gender may affect the outcome of M. tuberculosis infection. TLR2 gene may influence the development of PTB and TBM by different immune mechanisms.