A Study on Voice Measures in Patients with Parkinson's Disease.

PURPOSE: This research aims to identify acoustic features which can distinguish patients with Parkinson's disease (PD patients) and healthy speakers. METHODS: Thirty PD patients and 30 healthy speakers were recruited in the experiment, and their speech was collected, including three vowels (/i/, /a/, and /u/) and nine consonants (/p/, /pÊ°/, /t/, /tÊ°/, /k/, /kÊ°/, /l/, /m/, and /n/). Acoustic features like fundamental frequency (F0), Jitter, Shimmer, harmonics-to-noise ratio (HNR), first formant (F1), second formant (F2), third formant (F3), first bandwidth (B1), second bandwidth (B2), third bandwidth (B3), voice onset, voice onset time were analyzed in our experiment. Two-sample independent t test and the nonparametric Mann-Whitney U (MWU) test were carried out alternatively to compare the acoustic measures between the PD patients and healthy speakers. In addition, after figuring out the effective acoustic features for distinguishing PD patients and healthy speakers, we adopted two methods to detect PD patients: (1) Built classifiers based on the effective acoustic features and (2) Trained support vector machine classifiers via the effective acoustic features. RESULTS: Significant differences were found between the male PD group and the male health control in vowel /i/ (Jitter and Shimmer) and /a/ (Shimmer and HNR). Among female subjects, significant differences were observed in F0 standard deviation (F0 SD) of /u/ between the two groups. Additionally, significant differences between PD group and health control were also found in the F3 of /i/ and /n/, whereas other acoustic features showed no significant differences between the two groups. The HNR of vowel /a/ performed the best classification accuracy compared with the other six acoustic features above found to distinguish PD patients and healthy speakers. CONCLUSIONS: PD can cause changes in the articulation and phonation of PD patients, wherein increases or decreases occur in some acoustic features. Therefore, the use of acoustic features to detect PD is expected to be a low-cost and large-scale diagnostic method.

A composite semiparametric homogeneity test for the distributions of multigroup interval-bounded longitudinal data.

Motivated by comparing the distribution of longitudinal quality of life (QoL) data among different treatment groups from a cancer clinical trial, we propose a semiparametric test statistic for the homogeneity of the distributions of multigroup longitudinal measurements, which are bounded in a closed interval with excess observations taking the boundary values. Our procedure is based on a three-component mixed density ratio model and a composite empirical likelihood for the longitudinal data taking values inside the interval. A nonparametric bootstrap method is applied to calculate the p-value of the proposed test. Simulation studies are conducted to evaluate the proposed procedure, which show that the proposed test is effective in controlling type I errors and more powerful than the procedure which ignores the values on the boundaries. It is also robust to the model mispecification than the parametric test. The proposed procedure is also applied to compare the distributions of the scores of Physical Function subscale and Global Heath Status between the patients randomized to two treatment groups in a cancer clinical trial.

Relationship between temporal dynamics of intrinsic brain activity and motor function remodeling in patients with acute BGIS.

Background: patients with acute basal ganglia ischemic stroke (BGIS) show changes in local brain activity represented by the amplitude of low-frequency fluctuation (ALFF), but the time-varying characteristics of this local nerve activity are still unclear. This study aimed to investigate the abnormal time-varying local brain activity of patients with acute BGIS by using the ALFF method combined with the sliding-window approach. Methods: In this study, 34 patients with acute BGIS with motor dysfunction and 44 healthy controls (HCs) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) was employed to detect the alterations in brain activity induced by acute BGIS patients. A two-sample t-test comparison was performed to compare the dALFF value between the two groups and a Spearman correlation analysis was conducted to assess the relationship between the local brain activity abnormalities and clinical characteristics. Results: Compared with HCs, the activity of neurons in the left temporal pole (TP), parahippocampal gyrus (paraHIP), middle occipital gyrus (MOG), dorsolateral superior frontal gyrus (SFGdl), medial cingulate cortex (MCC), right rectus, precuneus (PCu) and right cerebellum crus1 were significantly increased in patients with BGIS. In addition, we found that there was a negative correlation (r = -0.458, p = 0.007) between the dALFF value of the right rectus and the scores of the National Institutes of Health Stroke Scale (NIHSS), and a positive correlation (r = 0.488, 0.499, p < 0.05) with the scores of the Barthel Index scale (BI) and the Fugl Meyer motor function assessment (FMA). ROC analysis results demonstrated that the area under the curves (AUC) of the right rectus was 0.880, p<0.001. Conclusion: The pattern of intrinsic brain activity variability was altered in patients with acute BGIS compared with HCs. The abnormal dALFF variability might be a potential tool to assess motor function in patients with acute BGIS and potentially inform the diagnosis of this disease.

Increased functional connectivity coupling with supplementary motor area in blepharospasm at rest.

OBJECTIVE: To explore the abnormalities of brain function in blepharospasm (BSP) and to illustrate its neural mechanisms by assuming supplementary motor area (SMA) as the entry point. METHODS: Twenty-five patients with BSP and 23 controls underwent resting-state functional MRI, seed-based functional connectivity (FC), correlation analysis, receiver operating characteristic curve (ROC) analysis, and support vector machine (SVM) were applied to process the data. RESULTS: Patients showed that the left medial prefrontal cortex (MPFC), left lingual gyrus, right cerebellar crus I, and right lingual gyrus/cerebellar crus I had enhanced FC with the left SMA, whereas the right inferior temporal gyrus (ITG) had enhanced FC with the right SMA relative to controls. The FC between the left MPFC and left SMA was positively correlated with symptomatic severity. The ROC analysis verified that the abnormal FCs demonstrated in this study can separate patients and controls at high sensitivity and specificity. SVM analysis exhibited that combined FCs of the left SMA were optimal for distinguishing patients and control group at the accuracy of 89.58%, with sensitivity of 92.00% and specificity of 86.96%. CONCLUSIONS: Several brain networks partake in the neurobiology of BSP. SMA plays a vital role in several brain networks and might be the key pathogenic factor in BSP. SIGNIFICANCE: Providing novel evidence for the engagement of the MPFC in the motor symptoms of BSP, enhancing credibility of the thesis that SMA regulates the neurobiology of BSP, and providing ideas of screening susceptible population of BSP using neuroimaging.

Liquid biopsy: circulating tumor DNA monitors neoadjuvant chemotherapy response and prognosis in stage II/III gastric cancer.

A good response to neoadjuvant chemotherapy (NACT) is strongly associated with a higher curative resection rate and favorable outcomes for patients with gastric cancer (GC). We examined the utility of serial circulating tumor DNA (ctDNA) testing for monitoring NACT response and prognosis in stage II-III GC. Seventy-nine patients were enrolled to receive two cycles of NACT following gastrectomy with D2-lymphadenectomy. Plasma at baseline, post-NACT, and after surgery, and tissue at pretreatment and surgery were collected. We used a 425-gene panel to detect genomic alterations (GAs). Results show that the mean cell-free DNA concentration of patients with clinical stage III was significantly higher than patients with stage II (15.43 ng·mL-1 vs 14.40 ng·mL-1 ). After receiving NACT and surgery, the overall detection rate of ctDNA gradually reduced (59.5%, 50.8%, and 47.4% for baseline, post-NACT, and postsurgery). The maximum variant allele frequency (max-VAF) and the number of GAs decreased from 0.50% to 0.08% and from 2.9 to 1.7 after NACT. For patients with a partial response after NACT, the max-VAF and the number of GAs declined significantly, but they increased for patients with progressive disease. Patients with detectable ctDNA at baseline, after NACT, or after surgery have a worse overall survival (OS) than patients with undetectable ctDNA. The estimated 3-year OS was 73% for the post-NACT ctDNA-negative patients and 34% for ctDNA-positive. Patients with perpetual negative ctDNA before and after NACT have the best prognosis. In conclusion, ctDNA was proposed as a potential biomarker to predict prognosis and monitor the NACT response for stage II-III GC patients.

Cerebral Gray Matter Volume Changes in Patients with Neuropathic Pain from Total Brachial Plexus Injury.

INTRODUCTION: Total brachial plexus injury not only significantly affects the motor and sensory function of the affected upper limbs but also causes further physical and mental damage to patients with long-term intractable pain. Previous studies mainly focused on the surgical treatment, while only a few paid attention to the intractable neuropathic pain caused by this injury. Changes in the volume of gray matter in the brain are thought to be associated with chronic neuropathic pain. METHODS: Voxel-based morphometry analysis was used to compare the difference in cerebral gray matter volume between total brachial plexus injury patients with neuropathic pain and healthy controls. Correlations between pain duration, pain severity, and GM changes were analyzed. RESULTS: The volume of cerebral gray matter in the patient group was decreased significantly in multiple regions, including the parahippocampal gyrus, paracentric lobule, inferior frontal gyrus, auxiliary motor cortex, middle occipital gyrus, right middle temporal gyrus, while it was increased in the insular, pons, middle frontal gyrus, cingulate gyrus, inferior parietal lobule, bilateral thalamus, and globus pallidus. There were no significant correlations between pain duration and rGMV changes, while a positive correlation was observed between pain severity and rGMV changes in one specific region, involving the anterior cingulate cortex. CONCLUSION: Total brachial plexus injury patients with chronic pain have widespread regions of gray matter atrophy and hypertrophy. The only positive correlation was observed between pain severity and rGMV changes in one specific region, suggesting that nociceptive stimuli trigger a variety of nonpain-specific processes, which confirms the multidimensional nature of pain.

Data-driven learning to identify biomarkers in bipolar disorder.

BACKGROUND AND OBJECTIVE: Bipolar disorder (BD) is one of the primary causes of disability globally and can be easily misdiagnosed as schizophrenia or major depression due to their similar symptoms. Hence, it is of great significance to explore the pathogenesis of BD. Statistical analysis is currently the most common method for exploring the neuropathological mechanisms of psychiatric disorders. However, this method only considers the relationship between groups and does not reflect the individual-level diagnosis. Therefore, we developed machine learning algorithms to measure pathological brain changes in psychiatric disorders. METHODS: An autoencoder and a feature selection method are proposed to identify the abnormal structural patterns of BD in this study. The autoencoder was constructed using structural imaging data from 1113 healthy controls, which aims to define the normal range of anatomical deviations to distinguish healthy individuals from BD patients. The biomarkers of BD were identified by the reconstruction errors in each brain region. The proposed feature selection (FS)-select framework aimed to determine the optimal FS method and identify the most reproducible feature associated with BD. RESULTS: We found that the left orbital region of the middle frontal gyrus had the greatest difference between healthy controls and BD patients using a trained autoencoder. The most reproducible feature was the left orbital region of the middle frontal gyrus by FS-select framework when using the different cross-validation strategies. CONCLUSIONS: A consistent result was obtained from the above two proposed methods wherein a significant difference between healthy controls and BD patients was identified in the left orbital region of the middle frontal gyrus.

Comparison of the somatic mutations between circulating tumor DNA and tissue DNA in Chinese patients with non-small cell lung cancer.

BACKGROUND: Non-invasive liquid biopsies of circulating tumor DNA (ctDNA) is a rapidly growing field in the research of non-small cell lung cancer (NSCLC). In this study, factors affecting the concordance of mutations in paired plasma and tissue and the detection rate of ctDNA in real-world Chinese patients with NSCLC were identified. METHODS: Peripheral blood and paired formalin-fixed paraffin-embedded tumor tissue samples from 125 NSCLC patients were collected and analyzed by sequencing 15 genes. Serological biomarkers were tested by immunoassay. RESULTS: The overall concordance between tumor and plasma samples and the detection rate of somatic mutations in ctDNA was 69.2% and 78.4%, respectively. The concordance and detection rate raised with clinical stage were stage I: 14.3%, 14.3%; stage II: 53.3%, 60.0%; stage III: 71.4%, 78.1%; stage IV: 74.1%, 85.2%. With increased tumor diameter, the concordance and detection rate raised from 33.33% to 71.64% and 33.33% to 80.8%, respectively. For patients with partial response, stable disease, progressive disease, and who were treatment-naïve, the concordance and detection rates were 0.0%, 62.7%, 75.2, 73.6%, and 16.7%, 61.9%, 83.3%, 86.5%, respectively. Serological markers: CEA, CA125, NSE, and CYFRA21-1 were significantly higher for patients with detectable somatic alterations in ctDNA than in those who were ctDNA negative (17.08 ng/mL vs. 3.95 ng/mL, 21.63 U/mL vs. 18.27 U/mL, 17.68 U/mL vs. 14.14 U/mL, and 6.55 U/mL vs. 3.81 U/mL, respectively). CONCLUSION: Advanced-stage, treatment naïve or poor therapy outcome, and large tumor size were associated with a high concordance and detection rate. Patients with detectable mutations in ctDNA had a higher level of carcinoembryonic antigen, CA125, NSE, and CYFRA21-1.

Frequency-Specific Changes of Amplitude of Low-Frequency Fluctuations in Patients with Acute Basal Ganglia Ischemic Stroke.

Objective: The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods: In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values. Results: Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores. Conclusion: In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

Comparing Brain Functional Activities in Patients With Blepharospasm and Dry Eye Disease Measured With Resting-State fMRI.

Background: Blepharospasm (BSP) and dry eye disease (DED) are clinically common diseases characterized by an increased blinking rate. A sustained eyelid muscle activity may alter the cortical sensorimotor concordance and lead to secondary functional changes. This study aimed to explore the central mechanism of BSP by assessing brain functional differences between the two groups and comparing them with healthy controls. Methods: In this study, 25 patients with BSP, 22 patients with DED, and 23 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scan. The amplitude of low-frequency fluctuations (ALFF) was applied to analyze the imaging data. Results: Analysis of covariance (ANCOVA) revealed widespread differences in ALFF across the three groups. In comparison with healthy controls, patients with BSP showed abnormal ALFF in the sensorimotor integration related-brain regions, including the bilateral supplementary motor area (SMA), left cerebellar Crus I, left fusiform gyrus, bilateral superior medial prefrontal cortex (MPFC), and right superior frontal gyrus (SFG). In comparison with patients with DED, patients with BSP exhibited a significantly increased ALFF in the left cerebellar Crus I and left SMA. ALFF in the left fusiform gyrus/cerebellar Crus I was positively correlated with symptomatic severity of BSP. Conclusions: Our results reveal that the distinctive changes in the brain function in patients with BSP are different from those in patients with DED and healthy controls. The results further emphasize the primary role of sensorimotor integration in the pathophysiology of BSP.

Abnormal Network Homogeneity in the Right Superior Medial Frontal Gyrus in Cervical Dystonia.

Background: Increasing evidence from modern neuroimaging has confirmed that cervical dystonia (CD) is caused by network abnormalities. Specific brain networks are known to be crucial in patients suffering from CD. However, changes in network homogeneity (NH) in CD patients have not been characterized. Therefore, the purpose of this study was to investigate the NH of patients with CD. Methods: An automated NH method was used to analyze resting-state functional magnetic resonance (fMRI) data from 19 patients with CD and 21 gender- and age-matched healthy controls (HC). Correlation analysis were conducted between NH, illness duration and symptom severity measured by the Tsui scale. Results: Compared with the HC group, CD patients showed a lower NH in the right superior medial frontal gyrus. No significant correlations were found between abnormal NH values and illness duration or symptom severity. Conclusion: Our findings suggest the existence of abnormal NH in the default mode network (DMN) of CD patients, and thereby highlight the importance of the DMN in the pathophysiology of CD.

Deep learning based automatic diagnosis of first-episode psychosis, bipolar disorder and healthy controls.

Neuroimaging data driven machine learning based predictive modeling and pattern recognition has been attracted strongly attention in biomedical sciences. Machine learning based diagnosis techniques are widely applied in diagnosis of neurological diseases. However, machine learning techniques are difficult to effectively extract deep information in neuroimaging data, resulting in low classification accuracy of mental illnesses. To address this problem, we propose a deep learning based automatic diagnosis first-episode psychosis (FEP), bipolar disorder (BD) and healthy controls (HC) method. Specifically, we design a convolutional neural network (CNN) framework to automatically diagnosis based on structural magnetic functional imaging (sMRI). Our dataset consists of 89 FEP patients, 40 BD patients and 83 HC. A three-way classifier (FEP vs. BD vs. HC) and three binary classifiers (FEP vs. BD, FEP vs. HC, BD vs. HC) are trained based on their gray matter volume images. Experiment results show that the performance of CNN-based method outperforms the classic classifiers both in two and three categories classification task. Our research reveals that abnormal gray matter volume is one of the main characteristics for discriminating FEP, BD and HC.

Voxel-Wise Brain-Wide Functional Connectivity Abnormalities in Patients with Primary Blepharospasm at Rest.

Background: Primary blepharospasm (BSP) is one of the most common focal dystonia and its pathophysiological mechanism remains unclear. An unbiased method was used in patients with BSP at rest to observe voxel-wise brain-wide functional connectivity (FC) changes. Method: A total of 48 subjects, including 24 untreated patients with BSP and 24 healthy controls, were recruited to undergo functional magnetic resonance imaging (fMRI). The method of global-brain FC (GFC) was adopted to analyze the resting-state fMRI data. We designed the support vector machine (SVM) method to determine whether GFC abnormalities could be utilized to distinguish the patients from the controls. Results: Relative to healthy controls, patients with BSP showed significantly decreased GFC in the bilateral superior medial prefrontal cortex/anterior cingulate cortex (MPFC/ACC) and increased GFC in the right postcentral gyrus/precentral gyrus/paracentral lobule, right superior frontal gyrus (SFG), and left paracentral lobule/supplement motor area (SMA), which were included in the default mode network (DMN) and sensorimotor network. SVM analysis showed that increased GFC values in the right postcentral gyrus/precentral gyrus/paracentral lobule could discriminate patients from controls with optimal accuracy, specificity, and sensitivity of 83.33%, 83.33%, and 83.33%, respectively. Conclusion: This study suggested that abnormal GFC in the brain areas associated with sensorimotor network and DMN might underlie the pathophysiology of BSP, which provided a new perspective to understand BSP. GFC in the right postcentral gyrus/precentral gyrus/paracentral lobule might be utilized as a latent biomarker to differentiate patients with BSP from controls.

Abnormal Spontaneous Brain Activities of Limbic-Cortical Circuits in Patients With Dry Eye Disease.

Whether brain function is altered in patients with dry eye disease (DED) remains unclear. Twenty patients with DED and 23 healthy controls (HCs) were scanned using resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) and support vector machine (SVM) were used to analyze the imaging data. Relative to the HCs, the patients with DED showed significantly increased ReHo values in the left inferior occipital gyrus (IOG), left superior temporal gyrus, and right superior medial prefrontal cortex, and significantly decreased ReHo values in the right superior frontal gyrus/middle frontal gyrus and bilateral middle cingulum (MC). SVM results indicated that the combination of ReHo values in the left MC and the left IOG in distinguishing patients with DED from HCs had a sensitivity of 95.00%, a specificity of 91.30%, and an accuracy of 93.02%. The present study found that the patients with DED had abnormal ReHo values in the limbic-cortical circuits. A combination of ReHo values in the left MC and the left IOG could be applied as a potential imaging biomarker to distinguish patients with DED from HCs. The dysfunction of limbic-cortical circuits may play an important role in the pathophysiology of DED.

Reduced Global-Brain Functional Connectivity of the Cerebello-Thalamo-Cortical Network in Patients With Dry Eye Disease.

Background: The pathophysiology of patients with dry eye disease (DED) is associated with abnormal functional connectivity (FC). The present study aims to probe alterations of voxel-wise brain-wide FC in patient with DED at rest in an unbiased way. Method: A total of 20 patients with DED and 23 controls matched by age, sex, and years of education underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was adopted to analyze the images. Support vector machine (SVM) was utilized to differentiate the patients from the controls. Results: Compared with the controls, patients with DED exhibited decreased GFC in the right cerebellum lobule VIII/inferior semi-lunar lobule and left thalamus that belonged to the cerebello-thalamo-cortical network. The GFC values in the left thalamus were positively correlated to the illness duration (r = 0.589, p = 0.006) in the patients. Decreased GFC values in the left thalamus could be used to discriminate the patients from the controls with optimal accuracy, sensitivity and specificity (88.37, 85.00, and 91.30%). Conclusions: Our findings indicate that decreased GFC in the brain regions associated with cerebello-thalamo-cortical network may provide a new insight for understanding the pathological changes of FC in DED. GFC values in the left thalamus may be utilized as a potential biomarker to identify the patients from the controls.

Expression of a TMC6-TMC8-CIB1 heterotrimeric complex in lymphocytes is regulated by each of the components.

The TMC genes encode a set of homologous transmembrane proteins whose functions are not well understood. Biallelic mutations in either TMC6 or TMC8 are detected in more than half of cases of the pre-malignant skin disease epidermodysplasia verruciformis (EV). It is controversial whether EV induced by mutations in TMC6 or TMC8 originates from keratinocyte or lymphocyte defects. Quantification of TMC6 and TMC8 RNA levels in various organs revealed that lymphoid tissues have the highest levels of expression of both genes, and custom antibodies confirmed protein expression in mouse lymphocytes. To study the function of these proteins we generated mice with targeted deletion mutant alleles of Tmc6 or Tmc8 Either TMC6 or TMC8 deficiency induced a reduction in apparent molecular weight and/or amount of the other TMC molecule. Co-immunoprecipitation experiments indicated that TMC6 and TMC8 formed a protein complex in mouse and human T cells. MS and biochemical analysis demonstrated that TMC6 and TMC8 additionally interacted with the CIB1 protein to form TMC6-TMC8-CIB1 trimers. We demonstrated that TMC6 and TMC8 regulated CIB1 levels by protecting CIB1 from ubiquitination and proteasomal degradation. Reciprocally, CIB1 was needed for stabilizing TMC6 and TMC8 levels. These results suggest why inactivating mutations in any of the three human genes leads to similar clinical presentations. We also demonstrated that TMC6 and TMC8 levels are drastically lower and the proteins are less active in regulating CIB1 in keratinocytes than in T cells. Our study suggests that defects in lymphocytes may contribute to the etiology and pathogenesis of EV.

Dysregulation of MiR-30a-3p/Gastrin Enhances Tumor Growth and Invasion throughSTAT3/MMP11 Pathway in Gastric Cancer.

BACKGROUND: Gastrin (GAST) is a well-known hormone regulating gastric biofunctions in the secretion of acid and maintaining its structural integrity. Furthermore, the dysregulation of GAST is also involved in the development of various forms of cancer. However, there are some limitations for illustrating the cellular regulation of GAST and its regulatory mechanisms in gastric malignant transformation and the potential epigenetic regulators systematically. METHODS: We explored the role of GAST expression in gastric cancer (GC) and normal tissues with the clinical features and investigated the potential relationship between GAST and STAT3/MMP11 pathway by gain or loss of function analyses. Besides, based on our microRNA/mRNA expression profiles, miR-30a-3p was the potential epigenetic regulator and additional experiments were performed to identify the hypothesis. RESULTS: Elevated GAST expression was frequently detected in GC and was associated with worse outcomes (p<0.001). And we firstly demonstrated that GAST was negatively regulated by miR-30a-3p. Moreover, GAST induced GC cell proliferation, migration and invasion mediating STAT3/MMP11 pathway in this study. CONCLUSION: MiR-30a-3p was the promising suppressor gene through negatively regulating the expression of GAST, and dysregulation of GAST was a prognostic signature associated cell proliferation and metastasis through STAT3/MMP11 pathway in GC.

Structural characterization of Lanzhou lily (Lilium davidii var. unicolor) polysaccharides and determination of their associated antioxidant activity.

BACKGROUD: The Lanzhou lily (Lilium davidii var. unicolor) is the only Lilium species that is used for both culinary and medicinal purposes in China. Its bulbs contain various bioactive substances, such as polysaccharides, saponins and colchicine. Lanzhou lily polysaccharides are known to have anti-immunity, anti-tumor and anti-oxidation functions. RESULTS: The present study used a Box-Behnken design to optimize the ultrasound-assisted extraction of Lanzhou lily polysaccharides. Compared to other enzymes, trypsin significantly increased the polysaccharide yields, whereas the protein content of polysaccharides extracted with trypsin was the lowest. Monosaccharide mainly includes glucose (> 50%) and mannose (> 10%). 1,1-Diphenyl-2-picrylhydrazyl radical scavenging activity, chelating activity, total antioxidant capacity and hydroxyl radical scavenging activity of Lanzhou lily polysaccharides extracted with trypsin were stronger than those extracted without enzymes (control). Structural characteristics of Lanzhou lily polysaccharides extracted with trypsin and extracted without enzymes were characterized by scanning electron microscopy and nuclear magnetic resonance spectroscopy. When water extracted polysaccharide and trypsin extracted polysaccharide concentrations were 200 µg mL-1 , Raw264.7 proliferation rates were 101.69% and 159.41%, respectively. CONCLUSION: The Lanzhou lily polysaccharide was identified as α-(1 → 6)-d-glucan. Consequently, the effects of both potential antioxidant and proliferative activity of trypsin are significant. © 2020 Society of Chemical Industry.

Relationships between abnormal neural activities and cognitive impairments in patients with drug-naive first-episode schizophrenia.

BACKGROUND: Prior resting state functional Magnetic Resonance Imaging studies (rs-fMRI) via the regional homogeneity (ReHo) method have demonstrated inconsistent and conflicting results because of several confounding factors, such as small sample size, medicinal influence, and illness duration. Relationships between ReHo measures and cognitive impairments in patients with drug-naive First-Episode Schizophrenia (dn-FES) are rarely reported. This study was conducted to explore the correlations between ReHo measures and cognitive deficits and clinical symptoms in patients with dn-FES. METHODS: A total of 69 patients with dn-FES and 74 healthy controls were recruited. MATRICS Consensus Cognitive Battery (MCCB), Wechsler Adult Intelligence Scale (WAIS), and Positive And Negative Syndrome Scale (PANSS) were used to assess cognitive function, Intelligence Quotient (IQ), and clinical symptoms, respectively. The correlations between ReHo maps and cognitive deficits and the severity of symptoms were examined using strict correlation analysis. RESULTS: ReHo values in right Middle Frontal Gyrus (MFG) and Superior Frontal Gyrus (SFG) increased in dn-FES group, whereas ReHo values in right cuneus decreased. Correlation analysis showed that the ReHo values in right MFG positively correlated with attention/vigilance impairments, social cognition deficits, and the severity of clinical manifestations. CONCLUSIONS: These findings suggested that abnormal spontaneous activities in right MFG reflect illness severity and cognitive deficits, which also serve as a basis for establishing objective diagnostic markers and might be a clinical intervention target for treating patients with schizophrenia.

MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. It is characterized by serious lung inflammation or injury. Characterizing novel miRNAs implicated in ARDS pathogenesis may provide new therapeutic strategy for managing ARDS. METHODS: We employed LPS-induced lung injury model to profile miRNAs associated with ARDS. We isolated one miRNA candidate and characterized its role in lipopolysaccharide (LPS)-induced proinflammatory cytokine production in lung macrophages. We further evaluated its functional role in ARDS model by assessing histological change, neutrophil activation, tissue permeability and tumor necrosis factor alpha (TNFα) production. We also characterized its downstream target using luciferase assay, Western blotting, enzyme-linked immunosorbent assay and cell inflammation assay. RESULTS: Microarray profiling revealed miR-802 was significantly downregulated in ARDS mouse model. LPS-induced miR-802 downregulation was confirmed in lung macrophages. Overexpression of miR-802 significantly suppressed LPS-induced inflammatory cytokine production in vitro and alleviates LPS-induced acute lung injury in vivo. Peli2 was identified as a downstream target of miR-802 and found upregulated in ARDS model. Overexpressing Peli2 abolished the antagonizing effect of miR-802 on LPS-mediated inflammatory response. CONCLUSION: MiR-802 carried a protective role against LPS-induced acute lung injury by downregulating Peli2. MiR-802/Peli2 axis may act as intervening targets to manage ARDS.