Abnormal static and dynamic functional network connectivity in stable chronic obstructive pulmonary disease.

Objective: Many studies have explored the neural mechanisms of cognitive impairment in chronic obstructive pulmonary disease (COPD) patients using the functional MRI. However, the dynamic properties of brain functional networks are still unclear. The purpose of this study was to explore the changes in dynamic functional network attributes and their relationship with cognitive impairment in stable COPD patients. Materials and methods: The resting-state functional MRI and cognitive assessments were performed on 19 stable COPD patients and 19 age-, sex-, and education-matched healthy controls (HC). We conducted the independent component analysis (ICA) method on the resting-state fMRI data, and obtained seven resting-state networks (RSNs). After that, the static and dynamic functional network connectivity (sFNC and dFNC) were respectively constructed, and the differences of functional connectivity (FC) were compared between the COPD patients and the HC groups. In addition, the correlation between the dynamic functional network attributes and cognitive assessments was analyzed in COPD patients. Results: Compared to HC, there were significant differences in sFNC among COPD patients between and within networks. COPD patients showed significantly longer mean dwell time and higher fractional windows in weaker connected State I than that in HC. Besides, in comparison to HC, COPD patients had more extensive abnormal FC in weaker connected State I and State IV, and less abnormal FC in stronger connected State II and State III, which were mainly located in the default mode network, executive control network, and visual network. In addition, the dFNC properties including mean dwell time and fractional windows, were significantly correlated with some essential clinical indicators such as FEV1, FEV1/FVC, and c-reactive protein (CRP) in COPD patients. Conclusion: These findings emphasized the differences in sFNC and dFNC of COPD patients, which provided a new perspective for understanding the cognitive neural mechanisms, and these indexes may serve as neuroimaging biomarkers of cognitive performance in COPD patients.

HPV16 E6 gene polymorphisms and the functions of the mutation site in cervical cancer among Uygur ethnic and Han nationality women in Xinjiang, China.

BACKGROUND: To investigate the genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang, China; analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer. METHODS: The HPV16 E6 sequence was analyzed using the European standard prototype to perform an evolutionary tree. HPV16 E6-T295/T350, G295/G350, and T295/G350 GV230 vectors were stably transfected into cervical cancer C33A cells to analyze the cell proliferation, migration and invasion, apoptosis by CCK8 and clonogenic assays, transwell and cell scratch assays, FACS experiments. RESULTS: The total HPV infection rate was 26.390% (760/2879), whereas the Uygur 22.87% (196/857) and the Han was 27.89% (564/2022) (P < 0.05). Among 110 mutations, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the leucine changing to valine (L83V). Moreover, there were 7 cases of E6 gene mutated at nucleotide 295 (T295G) with aspartic changing to glutamic (D64E). When E6 vector(s) of mutations sites were transfected into C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. T295/G350-E6 was significantly stronger than G295/G350 and T295/T350, G295/G350 was significantly stronger than T295/T350 (P < 0.05). The T295/G350 had the strongest effect on C33A cells and G295/G350 was significantly stronger than T295/T350 (P < 0.05). CONCLUSIONS: The positive HPV infection rates differed between the Uygur and Han in Xinjiang, China, and the genotype distribution of infection was different. After transfecting C33A cells with different eukaryotic expression vectors, the T295/G350 mutation site promoted the proliferation, migration, and invasion of C33A cells to a greater extent than G295/G350; however, G295/G350 had a stronger effect than T295/T350.

The Value and Clinical Significance of ZNF582 Gene Methylation in the Diagnosis of Cervical Cancer.

INTRODUCTION: The aim of this study was to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of ZNF582 gene and cervical cancer and high risk HPV16/18 infection. METHODS: Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation-specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qPCR). RESULTS: Among 93 high-grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low. CONCLUSION: While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.

Intrinsic low-frequency oscillation changes in multiple-frequency bands in stable patients with chronic obstructive pulmonary disease.

Abnormal local spontaneous brain activity during the resting state has been observed in chronic obstructive pulmonary disease (COPD). However, it is still largely unclear whether the abnormalities are related to specific frequency bands. Our purpose was to explore intrinsic neural activity changes in different frequency bands by using the amplitude of low-frequency fluctuation (ALFF) method in stable COPD patients. Nineteen stable COPD patients and twenty gender-, age- and education-matched normal controls (NCs) underwent functional magnetic resonance imaging scans, cognitive function tests and lung function tests. Two different frequency bands (slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz) were calculated and analyzed for frequency-dependent intrinsic neural activity by using the ALFF method. A two-way analysis of variance test was used to compare the main effects of the groups and the frequency bands in the ALFF method. Further post-hoc t-tests were used to compare the differences between COPD patients and NCs in terms of the different frequency bands. A Pearson's correlation analysis was performed to explore the relationship between the altered ALFF brain areas in the different frequency bands and the clinical evaluations in the COPD patients. There were main effects of the groups including significantly higher ALFF values in the right superior temporal gyrus (STG), the bilateral cerebellum posterior lobe (CPL), the right lingual gyrus (LG) and the right brainstem, and as well as significantly decreased ALFF values in the right inferior parietal lobule (IPL) and the angular. The main effect of frequency was demonstrated in the CPL, the STG, the prefrontal cortex and the middle cingulate gyrus. Furthermore, COPD patients exhibited more widespread alterations in intrinsic brain activity in the slow-5 band than in the slow-4 band. Moreover, the abnormal intrinsic brain activity in the slow-4 and slow-5 bands were associated with PaCO2 in COPD patients. These current results indicated that COPD patients showed abnormal intrinsic brain activity in two different frequency bands, and abnormal intrinsic neuronal activity in different brain regions could be better detected by slow-5 band. These observations may provide a neoteric view into understanding the local neural psychopathology in stable COPD patients.

Abnormal intrinsic functional hubs and connectivity in stable patients with COPD: a resting-state MRI study.

Chronic obstructive pulmonary disease (COPD) affects a large population and is closely associated with cognitive impairment. However, the mechanisms of cognitive impairment in COPD patients have not been unraveled. This study investigated the change in patterns of intrinsic functional hubs using a degree centrality (DC) analysis. The connectivity between these abnormal hubs with the remaining brain was also investigated using functional connectivity (FC). Nineteen stable patients with COPD and 20 normal controls(NC) underwent functional magnetic resonance imaging (MRI) examinations and clinical and neuropsychologic assessments. We measured the voxel-wise DC across the whole brain gray matter and the seed-based FC between these abnormal hubs in the remaining brain matter; the group difference was calculated. A partial correlation analysis was performed to assess the relationship between the abnormal DC and clinical variables in COPD patients. Compared to NC, the patients with COPD exhibited significantly decreased DC in the right lingual gyrus (LG), bilateral supplementary motor area (SMA), and right paracentral lobule (PCL). A further seed-based FC analysis found that COPD patients demonstrated significantly decreased FC between these abnormal hubs in several brain areas, including the left cerebellum anterior lobe, left lingual gyrus, left fusiform gyrus, right insula, right inferior frontal gyrus, limbic lobe, cingulate gyrus, left putamen, lentiform nucleus, right precuneus, and right paracentral lobule. A partial correlation analysis showed that the decreased DC in the right PCL was positively correlated with the FEV1 and FEV1/FVC, and the decreased DC in the SMA was positively correlated with naming and pH in COPD patients. This study demonstrates that there are intrinsic functional hubs and connectivity alterations that may reflect the aberrant information communication in the brain of COPD patients. These findings may help provide new insight for understanding the mechanisms of COPD-related cognitive impairment from whole brain functional connections.

MR imaging to detect myelolipomas of the liver: A case report and literature review.

RATIONALE: Primary hepatic myelolipoma is a rare benign neoplasm comprising mature adipose tissue and marrow components in various proportions. Chemical shift imaging (CSI) can distinguish the lipid within the tumor clearly; however, there have been no reports on the CSI of hepatic myelolipoma. PATIENT CONCERN: A 20-year-old woman visited our hospital after discovering a space-occupying lesion in the liver with a history of more than 1 year. She felt distension pain and discomfort under the xiphoid process, accompanied by nausea, vomiting, and occasional chest oppression. DIAGNOSIS: The tumor showed a well-defined mass with a pseudocapsule and a heterogeneous appearance on both T1- and T2-weighted magnetic resonance (MR) images. CSI analysis showed a signal decline within the tumor. Based on the histopathology, the tumor was diagnosed as hepatic myelolipoma. INTERVENTIONS AND OUTCOMES: The patient underwent a right hepatectomy, and the postoperative vital signs were stable. Two weeks later, the patient was discharged safely. LESSONS: Although hepatic myelolipoma is extremely rare, this condition should be considered in differential diagnosis when CSI shows that hepatic lesions contain fatty.

Abnormal resting-state functional connectivity of amygdala subregions in patients with obstructive sleep apnea.

Background: The amygdala is one of the core areas of the emotional circuits. Previous neuroimaging studies have revealed that patients with obstructive sleep apnea (OSA) have aberrant structure and function in several brain areas (including the amygdala). However, the resting-state functional connectivity (rs-FC) of amgydala subregions remains uncertain. Objective: To determine whether aberrant rs-FC exists between the amygdala subregions and other brain areas and whether such abnormalities are related to emotional disorders and cognitive impairment in OSA. Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) data of 40 male severe OSA patients and 40 matched healthy controls (HCs) were collected. The rs-FC between the amygdala subregions and other brain areas was compared between the two groups. The correlations between aberrant rs-FC and clinical variables and neuropsychological assessments were evaluated. Results: Compared with the HCs, the OSA patients showed significantly increased rs-FC between the left dorsal amygdala (DA) and the anterior lobe of the cerebellum, among the left ventrolateral amygdala (VA), the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG), and between the right VA and the left IFG. However, significantly decreased rs-FC was observed between the right DA and the right prefrontal cortex (PFC) in OSA patients. No regional differences in rs-FC were found between the OSA patients and HCs in the bilateral medial amygdala (MA). Conclusion: In this study, male severe OSA patients showed complex rs-FC patterns in the amygdala subregions, which may be the result of OSA-related selective damage to the amygdala, and abnormal rs-FC between the amygdala subregions and brain regions associated with emotional, cognitive and executive functions may partly explain the affective deficits and cognitive impairment observed in male severe OSA patients.

Genetic variations in E6, E7 and the long control region of human papillomavirus type 16 among patients with cervical lesions in Xinjiang, China.

BACKGROUND: Xinjiang is one of the areas with the highest incidence of cervical cancer in China. Genetic variation in Human papillomavirus type 16 (HPV16) may increase the ability of the virus to mediate carcinogenesis and immune escape, which are risk factors for the progression of cervical cancer. We investigated polymorphism in HPV16 and the distribution of its sub-lineages in the region by analyzing the E6, E7 and long control region (LCR) gene sequences from women with HPV16-positive cervical samples in Xinjiang. METHODS: A total of 138 cases of cervical lesions and squamous cell carcinoma with infection of HPV16 virus were collected. The E6 and E7 genes and LCR of HPV16 virus were sequenced and compared with the HPV16 European prototype reference and other HPV16 mutants for single nucleotide polymorphisms. Neighbor-joining phylogenetic trees were constructed using E6, E7 and LCR sequences. RESULTS: Fourteen missense mutations were found in the E6 gene; the loci with the highest mutation frequency were T350G (36/75, 48%) and T178G (19/75, 25.3%). In the E7 gene, the locus with the highest mutation frequency was A647G (18/75, 24%). A total of 33 polymorphic sites were found in the LCR, of which T7447C (39/95, 40.1%) was the most frequent. CONCLUSION: HPV16 in Xinjiang is mainly of the European variant, followed by the Asian variant type; no Africa 1, 2 or Asia-America variant types were found.

Disrupted resting-state spontaneous neural activity in stable COPD.

INTRODUCTION AND AIM: Abnormal brain structure and function in COPD has been reported on MRI. However, the deficit in local synchronization of spontaneous activity in patients with stable COPD remains unknown. The main aim of the present study was to explore spontaneous brain activity in patients with COPD compared with normal controls using the regional homogeneity (ReHo) method based on resting-state functional MRI. METHODS: Nineteen patients with stable COPD and 20 well-matched (including age, sex, and number of years of education) normal controls who were recruited for the present study underwent resting-state functional MRI examinations and a series of neuropsychological and clinical assessments. The ReHo method was used to assess the strength of local brain signal synchrony. The mean ReHo values in brain areas with abnormal ReHo were evaluated with a receiver operating characteristic curve. The relationships between the brain regions with altered ReHo values and the clinical and neuropsychological parameters in COPD patients were assessed using Pearson's correlation. RESULTS: Patients with COPD showed significantly lower ReHo values in the left occipital lobe and the right lingual, bilateral precuneus, and right precentral gyrus. The result of receiver operating characteristic curve analysis showed that the altered average ReHo values have high efficacy for distinguishing function. The mean lower ReHo values in the precuneus gyrus showed a significant positive correlation with FEV1%, FEV1/FVC, and orientation function but a significant negative correlation with arterial partial pressure of carbon dioxide. CONCLUSION: The COPD patients demonstrated abnormal synchrony of regional spontaneous activity, and the regions with abnormal activity were all correlated with visual processing pathways, which might provide us with a new perspective to further understand the underlying pathophysiology of cognitive impairment in patients with COPD.

Abnormal intrinsic brain activities in stable patients with COPD: a resting-state functional MRI study.

OBJECTIVE: The majority of previous neuroimaging studies have reported both structural and functional changes in COPD, whereas the intrinsic low-frequency oscillations changes and the relationship between the abnormal brain regions and the clinical performances remain unknown. The present study was conducted with the aim of evaluating the intrinsic brain activity in COPD patients using the amplitude of low-frequency fluctuation (ALFF) method. METHODS: All participants, including 19 stable patients with COPD and 20 normal controls (NCs) matched in age, sex, and education, underwent resting-state functional MRI scans and performed cognitive function tests and respiratory functions tests. The local spontaneous brain activity was examined using the voxel-wise ALFF. Pearson's correlation analysis was used to investigate the relationships between the brain regions with altered ALFF signal values and the clinical features in COPD patients. RESULTS: Compared with the NCs, COPD patients showed significantly lower cognitive function scores. Also, lower ALFF areas in the cluster of the posterior cingulate cortex (PCC) and precuneus, as well as a higher ALFF area in the brainstem were also found in COPD patients. The mean ALFF values in the PCC, precuneus, and brainstem showed high sensitivity and specificity in operating characteristic curves analysis, which might have the ability to distinguish COPD from NCs. Meanwhile, the mean signal values of the lower ALFF cluster displayed significant positive correlations with FEV1/FVC proportion and significant negative correlation with PaCO2; the higher ALFF cluster showed significant positive correlation with FEV1 proportion in COPD. CONCLUSION: According to the results of the present study, the COPD patients showed abnormal intrinsic brain activities in the precuneus, PCC, and brainstem, which might provide useful information to better understand the underlying pathophysiology of cognitive impairment.

Aberrant brain functional connectome in patients with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is accompanied by widespread abnormal spontaneous regional activity related to cognitive deficits. However, little is known about the topological properties of the functional brain connectome of patients with OSA. This study aimed to use the graph theory approaches to investigate the topological properties and functional connectivity (FC) of the functional connectome in patients with OSA, based on resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Forty-five male patients with newly diagnosed untreated severe OSA and 45 male good sleepers (GSs) underwent a polysomnography (PSG), clinical evaluations, and rs-fMRI scans. The automated anatomical labeling (AAL) atlas was used to construct the functional brain connectome. The topological organization and FC of brain functional networks in patients with OSA were characterized using graph theory methods and investigated the relationship between functional network topology and clinical variables. RESULTS: Both the patients with OSA and the GSs exhibited high-efficiency "small-world" network attributes. However, the patients with OSA exhibited decreased σ, γ, Eglob; increased Lp, λ; and abnormal nodal centralities in several default-mode network (DMN), salience network (SN), and central executive network (CEN) regions. However, the patients with OSA exhibited abnormal functional connections between the DMN, SN, and CEN. The disrupted FC was significantly positive correlations with the global network metrics γ and σ. The global network metrics were significantly correlated with the Epworth Sleepiness Scale (ESS) score, Montreal Cognitive Assessment (MoCA) score, and oxygen desaturation index. CONCLUSION: The findings suggest that the functional connectome of patients with OSA exhibited disrupted functional integration and segregation, and functional disconnections of the DMN, SN, and CEN. The aberrant topological attributes may be associated with disrupted FC and cognitive functions. These topological abnormalities and disconnections might be potential biomarkers of cognitive impairments in patients with OSA.

Sorption of an anionic dye by uncalcined and calcined layered double hydroxides: a case study.

Layered double hydroxides (LDHs) with a Mg/Al molar ratio of 2:1 were synthesized by using a co-precipitation method and their calcined products (CLDHs) were obtained by heating Mg/Al-LDHs at 500 degrees C. Sorption of a weak acid dye, Brilliant Blue R (BBR), by LDHs and CLDHs indicated equilibrium time required for BBR sorption by CLDHs was less than 12h, regardless of initial concentration of BBR, whereas BBR sorption by LDHs was longer than 20 h. Sorption capacity of CLDHs was much larger than that of LDHs. Therefore, CLDHs could be used to remove anionic dyes of relatively high concentrations while LDHs may only be used to remove anionic dyes of low concentrations. Isotherms for BBR sorption by CLDHs and LDHs were well described using the Freundlich and Langmuir equations, respectively. When the initial pH of BBR solutions was lower than 8.0, the final pH of the solution after sorption was enhanced and stabilized at 10.6-10.8. The effect of initial pH (<8.0) on BBR removal was negligible, which would be environmentally important for precipitation/co-precipitation of co-existing metal cations. The effects of both Cl- and SO4(2-) on BBR sorption by CLDHs were minimal; but the presence of CO(3)2- markedly reduced BBR removal. Thermal regeneration for re-use of LDHs and CLDHs after BBR sorption was feasible only within the first two cycles, after which the regenerated materials suffered from a large loss in their sorption capacities.