Objective Neurophysiological Indices for the Assessment of Chronic Tinnitus Based on EEG Microstate Parameters.

Chronic tinnitus is highly prevalent but lacks precise diagnostic or effective therapeutic standards. Its onset and treatment mechanisms remain unclear, and there is a shortage of objective assessment methods. We aim to identify abnormal neural activity and reorganization in tinnitus patients and reveal potential neurophysiological markers for objectively evaluating tinnitus. By way of analyzing EEG microstates, comparing metrics under three resting states (OE, CE, and OECEm) between tinnitus sufferers and controls, and correlating them with tinnitus symptoms. This study reflected specific changes in the EEG microstates of tinnitus patients across multiple resting states, as well as inconsistent correlations with tinnitus symptoms. Microstate parameters were significantly different when patients were in OE and CE states. Specifically, the occurrence of Microstate A and the transition probabilities (TP) from other Microstates to A increased significantly, particularly in the CE state (32-37%, p ≤ 0.05 ); and both correlated positively with the tinnitus intensity. Nevertheless, under the OECEm state, increases were mainly observed in the duration, coverage, and occurrence of Microstate B (15-47%, ), which negatively correlated with intensity ( [Formula: see text]-0.513, ). Additionally, TPx between Microstates C and D were significantly reduced and positively correlated with HDAS levels ( [Formula: see text] 0.548, ). Furthermore, parameters of Microstate D also correlated with THI grades ( [Formula: see text]-0.576, ). The findings of this study could offer compelling evidence for central neural reorganization associated with chronic tinnitus. EEG microstate parameters that correlate with tinnitus symptoms could serve as neurophysiological markers, contributing to future research on the objective assessment of tinnitus.

Electrical nerve stimulation for sensory-neural pathway reconstruction in upper-limb amputees.

Introduction: The loss of the neural sensory function pathways between the stump limbs and the brain greatly impacts the rehabilitation of limb function and the daily lives of amputees. Non-invasive physical stressors, such as mechanical pressure and transcutaneous electrical nerve stimulation (TENS), could be potential solutions for recovering somatic sensations in amputees. Previous studies have shown that stimulating the residual or regenerated nerves in the stumps of some amputees can produce phantom hand sensations. However, the results are inconclusive due to unstable physiological responses caused by inaccurate stimulus parameters and positions. Methods: In this study, we developed an optimal TENS strategy by mapping the distribution of the nerves in the stump skin that elicitsphantom sensations known as a "phantom hand map." We evaluated the effectiveness and stability of the confirmed stimulus configuration in a long-term experiment using single- and multi-stimulus paradigms. Additionally, we evaluated the evoked sensations by recording electroencephalograms (EEG) and analyzing brain activities. Results: The results demonstrated that various types of intuitive sensations for amputees could be stably induced by adjusting TENS frequencies, particularly at 5 and 50 Hz. At these frequencies, 100% stability of sensory types was achieved when the stimuli were applied to two specific locations on the stump skin. Furthermore, at these locations, the stability of sensory positions was 100% across different days. Moreover, the evoked sensations were objectively supported by specific patterns of event-related potentials in brain responses. Discussion: This study provides an effective method for developing and evaluating physical stressor stimulus strategies, which could play an important role in the somatosensory rehabilitation of amputees and other patients suffering from somatomotor sensory dysfunction. The paradigm developed in this study can provide effective guidelines for stimulus parameters in physical and electrical nerve stimulation treatments for a variety of symptoms related to neurological disorders.

Examination of a Chinese-made cryptococcal glucuronoxylomannan antigen test in serum and bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients.

BACKGROUND: We presented the performance of a Chinese-made cryptococcal glucuronoxylomannan (GXM) antigen test using serum and bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. METHODS: Between February 2017 and January 2019, HIV-negative patients with pulmonary cryptococcosis were recruited and followed-up every three months, including completion of a chest CT examination and collection of serum and BALF samples. RESULTS: Here, thirty-seven confirmed and ten clinically diagnosed patients were recruited. Furthermore, samples from 174 noncryptococcosis patients that may cause false positives were also collected. The sensitivity of a lateral flow assay (LFA) for detecting cryptococcal GXM antigen in serum and BALF samples from confirmed cases was 97% and 95%, respectively, and the specificity was 98.2% and 93%, respectively, and the differences in these values between the BALF and serum samples were not significant. The serum cryptococcal GXM antigen value showed a positive correlation (r: 0.581, p < 0.001) with pulmonary lesion size, while the BALF value showed no correlation (r: 0.253, p: 0.13). The positivity rate of BALF was higher than that of serum when the diameter of the pulmonary lesion was small (diameter less than 20 mm). Moreover, the serum cryptococcal GXM antigen levels showed an overall decreasing trend with the decrease in pulmonary lesion size after antifungal therapy in patient follow-up. CONCLUSIONS: The Chinese-made cryptococcal GXM antigen test has better sensitivity and specificity for diagnosing pulmonary cryptococcosis in the HIV-negative Chinese population, and it could be used to diagnose and to monitor this disease.

Exhaled Volatile Organic Compounds for Identifying Patients With Chronic Pulmonary Aspergillosis.

Background: Diagnosing chronic pulmonary aspergillosis is a major challenge in clinical practice. The development and validation of a novel, sensitive and specific assay for diagnosing chronic pulmonary aspergillosis is urgently needed. Methods: From April 2018 to June 2019, 53 patients with chronic pulmonary aspergillosis (CPA), 32 patients with community-acquired pneumonia (CAP) and 48 healthy controls were recruited from the First Affiliated Hospital of Guangzhou Medical University. Clinical characteristics and samples were collected at enrollment. All exhaled breath samples were analyzed offline using thermal desorption single-photon ionization time-of-flight mass spectrometry; to analyze the metabolic pathways of the characteristic volatile organic compounds, serum samples were subjected to ultrahigh-performance liquid chromatography. Results: We identified characteristic volatile organic compounds in patients with chronic pulmonary aspergillosis, which mainly consisted of phenol, neopentyl alcohol, toluene, limonene and ethylbenzene. These compounds were assessed using a logistic regression model. The sensitivity and specificity were 95.8 and 96.9% for discriminating patients in the CPA group from those in the CAP group and 95.8 and 97.9% for discriminating patients in the CPA group from healthy controls, respectively. The concentration of limonene (m/z 136) correlated significantly positively with anti-Aspergillus fumigatus IgG antibody titers (r = 0.420, P < 0.01). After antifungal treatment, serum IgG and the concentration of limonene (m/z 136) decreased in the subgroup of patients with chronic pulmonary aspergillosis. Conclusions: We identified VOCs that can be used as biomarkers for differential diagnosis and therapeutic response prediction in patients with chronic pulmonary aspergillosis.

Long noncoding RNA ZFAS1 silencing alleviates rheumatoid arthritis via blocking miR-296-5p-mediated down-regulation of MMP-15.

Rheumatoid arthritis (RA), a chronic inflammatory disease, deprives patients' walking ability and reduces their life quality worldwide. Though recent studies have indicated the role of long noncoding RNA (lncRNA) ZFAS1 in several diseases, however, its role in RA remains uncharacterized. The present study aimed to unravel the the effect of ZFAS1 on RA. Herein, the RA mouse model and the human RA synoviocyte MH7A cell lines stimulated with TNF-α were established. ZFAS1 was next determined to be highly expressed in the mice with RA-like symptoms and TNF-α-stimulated MH7A cells while inhibiting ZFAS1 was demonstrated to promote proliferation and suppress apoptosis of MH7A cells. Furthermore, ZFAS1 knockdown exerted anti-inflammation effect in vitro and in vivo and reduced the arthritis index value. Moreover, RNA immunoprecipitation and dual-luciferase reporter assays identified the binding of ZFAS1 to microRNA (miR)-296-5p as well as the binding of miR-296-5p to matrix metalloproteinase-15 (MMP-15). Of note, ZFAS1 could bind miR-296-5p to up-regulate the expression of MMP-15. Our results from in vitro and in vivo experiments demonstrated silencing ZFAS1 mitigated RA-like symptoms such as inflammation and hyperplasia via miR-296-5p-dependent inhibition of MMP-15. Taken altogether, our study confirmed that ZFAS1 involved in RA progression by competitively binding to miR-296-5p and regulating MMP-15 expression.

Multiple-Frequency Matching Treatment Strategy for Tinnitus.

OBJECTIVE: The first aim was to integrate commonly used tinnitus measures into a comprehensive questionnaire. Second, the effectiveness of a masking therapy based on multiple-frequency matching was verified in a clinical study. This study investigated the feasibility of a new treatment strategy for tinnitus, with two main foci. MATERIALS AND METHODS: Compare multiple-frequency matching with traditional masking therapy (Single-frequency matching) through clinical trials. The analysis indicated that the reliability and construct validity of the comprehensive questionnaire need to be improved, and the feasibility of the integration attempt remains uncertain. RESULTS: The clinical results showed that the multiple-frequency matching method was more effective than single-frequency matching for tinnitus treatment. CONCLUSION: The multiple-frequency approach should be used more often with tinnitus masking to promote the patients' recovery.

Curcumin modulation of the activation of PYK2 in peripheral blood mononuclear cells from patients with lupus nephritis.

INTRODUCTION: Proline-rich tyrosine kinase 2 (PYK2) provides important signals during the activation of lymphocytes, which is essential in autoimmune diseases. Systemic lupus erythematosus (SLE) is a representative autoimmune disease, and lupus nephritis (LN) is one of its most severe complications. Although glucocorticoid-binding immuno-suppression is the first-line therapy for patients with LN, the common and severe side effects of such treatment call for new strategies to improve long-term prognosis and life quality for these patients. Curcumin has been used to treat autoimmune disease with good curative effect, but little is known about the effect of curcumin on LN patients. Our aim was to investigate the mechanism of curcumin for management of LN, specifically regarding the PYK2 pathways. MATERIAL AND METHODS: Freshly isolated peripheral blood mononuclear cells (PBMCs) from 20 LN patients and 20 healthy individuals were cultured and stimulated with either PMA, PMA+TyrA9 (PYK2 specific inhibitor), or PMA+Curcumin, and with PBS as control. After 48 hours of incubation, cells were harvested and the expression of PYK2, p-PYK2, CD40L, CTLA-4, and PBMCs proliferation were measured. Then the expression and activation of PYK2 was evaluated using Western blot, the expression of costimulatory molecules CD40L and CTLA-4 protein was evaluated using flow cytometry, and PBMC proliferation was assessed using a [3H]-thymidine incorporation assay. RESULTS: Curcumin inhibited the expression and activation of PYK2 in PBMCs in patients with LN in vitro. The inhibition rate of curcumin was negatively correlated with the level of serum complement, but positively correlated with 24-h proteinuria. Curcumin also suppressed the expression of costimulatory molecules CD40L and CTLA-4, as well as PBMC proliferation. Interestingly, these effects were not reproduced on PBMC cultures of healthy subjects. CONCLUSIONS: The inhibition of PYK2 signalling protein may be one of the mechanisms underlying the action of curcumin in LN treatment.

[Expression of transforming growth factor beta 1 and conection tissue growth factor in ankylosing spondylitis].

OBJECTIVE: To investigate the expressions of transforming growth factor beta 1(TGF-ß1) /smad, connective tissue growth factor (CTGF), collagen I and collagen III in ankylosing spondylitis (AS). METHODS: Thirty patients with AS were included in the study. All the patients were performed with computed tomography-guided needle biopsy in sacroiiliac joint. Sera TGF-ß1 and CTGF were determined by enzyme-linked immunosorbent assay (ELISA). Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique to assess the expressions of TGF-ß1, p-smad3, smad7, CTGF, collagen I and collagen III in sacroiiliac joint tissue samples. RESULTS: In the AS patients, neither serum TGF-ß1 level nor serum CTGF level was found significantly different from that of the controls [(6.7±2.1)mg/L vs.(5.4±5.8)mg/L, P<0.05, (0.83±0.46)µg/L vs.(1.07±0.79 )µg/L, P<0.05]. In contrast to the healthy controls, TGF-ß1 and CTGF were found upexpressed in cytoplasm of inflammatory cells in pannus and bone marrow in sacroiliac tissue samples of patients with AS [(104.5±66.2) /HP vs. (24.4±9.3) /HP, (57.94±42.40) /HP vs. (2.67±2.52) /HP]. Meantime, p-smad3 was found expressed in the nuclear, while smad7 was detected to be downexpressed. Additionally, collagen I and collagen III were found upexpressed in bone, cartilage and ligament tissue. CONCLUSION: TGF-ß1, CTGF, collagen I and collagen III were upexpressed in sarcoiliac joints of AS patients. TGF-ß1/CTGF may play an important role in articular cartilage fibrosis and ossification of AS by smad signal pathyway.