Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy.

BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

Long noncoding RNA UCA1 regulates CCR7 expression to promote tongue squamous cell carcinoma progression by sponging miR-138-5p.

Tongue squamous cell carcinoma (TSCC) is a malignant tumor. Long noncoding RNAs (lncRNAs) have been proved to be involved in the regulation of the progression of various cancers. However, the mechanism of lncRNA urothelial cancer-associated 1 (UCA1) in the progression of TSCC remains unclear. The expression levels of UCA1, microRNA-138-5p (miR-138-5p), and CC chemokine receptor 7 (CCR7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion were detected using colony formation assay and transwell assay, respectively. Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related proteins and CCR7 protein. Moreover, the extracellular acidification rate (ECAR) of cells was measured by the Seahorse XF Extracellular Flux Analyzer, and the adenosine triphosphate (ATP) level, glucose uptake, and lactate produce of cells were tested by their corresponding assay kits. Further, the dual-luciferase reporter assay was used to confirm the interaction between miR-138-5p and UCA1 or CCR7. In addition, the effect of UCA1 on TSCC tumor growth in vivo was evaluated by animal experiments. We found that UCA1 and CCR7 were upregulated, while miR-138-5p was downregulated in TSCC tissues. Silenced UCA1 restrained the proliferation, migration, invasion, and glycolysis metabolism of TSCC cells. Similarly, knockdown of CCR7 also could suppress the progression of TSCC. Besides, UCA1 overexpression promoted TSCC progression, while this promotion effect could be reversed by CCR7 silencing. miR-138-5p could be sponged by UCA1 and could target CCR7. Additionally, miR-138-5p overexpression could reverse the promotion effect of overexpressed UCA1 on TSCC progression. Furthermore, the UCA1 knockdown reduced TSCC tumor growth in vivo. In conclusion, lncRNA UCA1 might function as an oncogene in TSCC through regulating the miR-138-5p/CCR7 axis, providing a new biomarker for TSCC treatment.

Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies.

Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.

Alterations in the intestinal microbiota of patients with severe and active Graves' orbitopathy: a cross-sectional study.

BACKGROUND: The intestinal microbiota was linked to autoimmune diseases. Graves' orbitopathy (GO) is an autoimmune disease that is usually associated with Graves' disease. However, information on the microbiome of GO patients is yet lacking. OBJECTIVES: To investigate whether GO patients differ from healthy controls in the fecal microbiota. DESIGN: A cross-sectional study. SETTING: 33 patients with severe and active GO and 32 healthy controls of Han nationality were enrolled between March 2017 and March 2018. METHODS: The Gut microbial communities of the fecal samples of GO patients and healthy controls were analyzed and compared by 16S rRNA gene sequencing. RESULTS: Community diversity (Simpson and Shannon) was significantly reduced in fecal samples from patients with GO as compared to controls (p < 0.05). The similarity observed while assessing the community diversity (PCoA) proposed that the microbiota of patients with GO differ significantly from those of controls (p < 0.05). At the phyla levels, the proportion of Bacteroidetes increased significantly in patients with GO (p < 0.05), while at the genus and species levels, significant differences were observed in the bacterial profiles between the two groups (p < 0.05). LIMITATIONS: Single-centered study design and limited fecal samples. CONCLUSIONS: The present study indicated distinctive features of the gut microbiota in GO patients. The study provided evidence for further exploration in the field of intestinal microbiota with respect to the diagnosis and treatment of GO patients by modifying the microbiota profile.

A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves' orbitopathy.

OBJECTIVE: Graves' orbitopathy (GO) is an inflammatory orbital disease of autoimmune origin with the potential to cause severe functional and psychosocial effects. The pathogenesis has not been fully elucidated. We investigated whether DNA methylation was associated with GO incidence in Chinese patients. MATERIALS AND METHODS: Six GO patients and six age-matched controls were recruited, and genome-wide DNA methylation patterns were analyzed in their peripheral blood. t tests were performed to determine differential methylated sites in genomic regions and the univariable logistic regression analyses was performed to evaluate their risk with GO incidence. Cluster analysis and principal component analysis (PCA) were performed to determine the effects of the extracted differentially methylated sites. RESULTS: One hundred and forty-eight differentially methylated sites were identified, including CD14 (fold change = 4.31, p = 0.005), IL17RE (fold change = 2.128, p = 0.005), and DRD4 (fold change = 0.25, p = 0.004), and were supported by cluster and PCA analyses. Univariable logistic regression analyses showed that the methylation patterns at 12 loci were associated with GO incidence. The relative risk per 1% decrease in methylation at ZCCHC6 and GLI3 was 0.15 (95% CI 0.03-0.91; p = 0.039) and 0.65 (95% CI 0.42-0.98; p = 0.042), respectively. Pearson correlation analyses demonstrated that methylation levels at IL17RE were positively associated with Clinical Activity Score (CAS) (r = 0.967, p < 0.05). CONCLUSIONS: Our results demonstrate that differential methylation levels at analyzed sites (genes) may be risk markers of GO. DNA methylation analysis could provide new insights into understanding the disease and provide new treatment strategies for GO in Chinese patients.

[Characteristics of Schizophrenia Patients' Homicide Behaviors and Their Correlations with Criminal Capacity].

OBJECTIVES: To explore the characteristics of schizophrenia patients' homicide behaviors and the influences of the assessments of criminal capacity. METHODS: Indicators such as demographic and clinical data, characteristics of criminal behaviors and criminal capacity from the suspects whom were diagnosed by forensic psychiatry as schizophrenia （n=110） and normal mental （n=70） with homicide behavior, were collected by self-made investigation form and compared. The influences of the assessments of criminal capacity on the suspects diagnosed as schizophrenia were also analyzed using logistic regression analysis. RESULTS: There were no significant statistical differences between the schizophrenic group and the normal mental group concerning age, gender, education and marital status （P>0.05）. There were significant statistical differences between the two groups concerning thought disorder, emotion state and social function before crime （P<0.05） and there were significant statistical differences in some characteristics of the case such as aggressive history （P<0.05）, cue, trigger, plan, criminal incentives, object of crime, circumstance cognition and self-protection （P<0.05）. Multivariate logistic regression analysis suggested that thought disorder, emotion state, social function, criminal incentives, plan and self-protection before crime of the schizophrenic group were positively correlated with the criminal capacity （P<0.05）. CONCLUSIONS: The relevant influences of psychopathology and crime characteristics should be considered comprehensively for improving the accuracy of the criminal capacity evaluation on the suspects diagnosed as schizophrenia with homicide behavior.

[Comparison of Criminal Characteristics in Depression Patients and Schizophrenics with Homicide Behavior].

OBJECTIVES: To explore the criminal characteristics of forensic psychiatry expertise in depression patients and schizophrenics with homicide behavior. METHODS: A total of 40 depression （depressive episode） patients and 50 schizophrenics with homicide behavior were randomly assigned into the study group and control group, respectively. Data of demographic and criminal characteristic of the two groups were collected by a self-designed questionnaire, and then were compared. RESULTS: There were no statistical differences in age, education level and career between study and control groups （P>0.05）. Compared with the control group, the victims in the study group were mainly the patient's children and parents, and most offenders had suicidal behavior after homicide （70%）. In study group, the motives of crime were mainly extended suicide and indirect suicide, and most offenders had attempted suicide （85%） and diminished capacity of criminal responsibility （70%）, which in control group had no capacity of criminal responsibility （56%）. Except for criminal site, there were statistical differences in other criminal characteristics between two groups （P<0.05）. CONCLUSIONS: There are different criminal characteristics between depression patients and schizophrenics with homicide behavior in forensic psychiatry, and these characteristics should be considered when these two diagnoses are distinguished in forensic psychiatry expertise.

Effect of inhaled MgSO4 on FEV1 and PEF in children with asthma induced by acetylcholine: a randomized controlled clinical trail of 330 cases.

OBJECTIVES: To determine the response of nebulized magnesium sulfate on the lung function of acetylcholine-induced asthma children. METHODS: Three hundred and thirty children of asthma with positive bronchial provocation test were randomly divided into three groups: magnesium sulfate, albuterol, and a combination of magnesium sulfate and albuterol. Lung function was compared between the three groups. RESULTS: Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) as percentage over predicted at 10 min and 20 min in albuterol and combination group were significantly improved when compared to magnesium group. The changes in FEV1 and PEF expressed as absolute and percentage over predicted was not statistically significant from baseline to 20 min in magnesium, albuterol, and combination of magnesium sulfate and albuterol. There was no significant adverse effect observed during the present study. CONCLUSION: Nebulized magnesium sulfate alone has a bronchodilatory effect in Ach-induced asthmatic children. The combination of MgSO4 and albuterol did not has a synergistic effect.

[Analysis on incidence trend of liver cancer in China, 2005-2016].

Objective: To understand the incidence trend of liver cancer in China from 2005 to 2016, and explore the correlation between the incidence trend of liver cancer and the incidence trend of hepatitis B. Methods: The incidence data of liver cancer in China from 2005 to 2016 were collected from the Annual Report of Cancer Registry in China. The incidence data of hepatitis B were collected from China Public Health Science Data Center. World standardized incidence rate (WSR) was calculated according to the World Segi's population. Joinpoint regression model was used to analyze the trend of WSR of liver cancer [measured by average annual percentage change (AAPC)]. The age-period-cohort model was fitted to analyze the age, period and cohort effects in people aged 20- years and above. Pearson correlation coefficient was used to explore the correlation between the incidence of liver cancer and the incidence of hepatitis B. Results: The crude incidence of liver cancer in China showed a trend of first increase before 2009 and then relatively stable. The world standardized morbidity rate of liver cancer in China decreased from 19.11 per 100 000 in 2005 to 17.74 per 100 000 in 2016 (AAPC=-0.5%, 95%CI: -1.3%-0.3%, P=0.240). The incidence of liver cancer in male decreased significantly (AAPC=-1.0%, 95%CI: -1.5%--0.5%, P=0.001). The incidence of liver cancer in women increased from 2005 to 2010 [annual percentage change (APC)=1.7%, 95%CI: -0.1%-3.4%, P=0.059] but showed a significant decrease trend from 2010 to 2016 (APC=-1.6%, 95%CI: -2.3%--1.0%, P=0.001). From 2005 to 2016, the incidence of liver cancer showed a decreasing trend in urban areas (AAPC=-0.3%, 95%CI: -0.8%-0.3%, P=0.316) and rural areas (AAPC=-3.9%, 95%CI: -4.4%--3.3%, P<0.001). Risk for liver cancer increased with age, while the period effect showed a trend of first increase then decrease and cohort effect showed a decrease trend. The morbidity rates of both hepatitis B and liver cancer showed decrease trends from 2009 to 2016, and there was a significant correlation (r=0.71, 95%CI: 0.01-0.94, P=0.048). Conclusions: From 2005 to 2016, the morbidity rate of liver cancer in China showed a decrease trend, and there were significant gender and urban-rural area specific differences. Age effect had a great impact on the risk for liver cancer. With the progress of population aging in China, liver cancer is still a public health problem, to which close attention needs to be paid.

Positioning error analysis of the fraxion localization system in the intracranial stereotactic radiotherapy of tumors.

OBJECTIVE: To investigate positioning error analysis of the Fraxion localization system in the intracranial stereotactic radiotherapy of tumors. METHODS: 64 patients were divided into two groups: a control group (36 patients with the standard thermoplastic mask) and a model group (28 patients with the Fraxion localization system). 3D images of the treated position were obtained by cone-beam computed tomography (CBCT). Positioning errors were obtained by, respectively, registering these two sets of CBCT images to planning CT images, using a 6°-freedom robotic patient positioning system (HexaPOD Evo RT System). The changes in positioning errors with the Fraxion localization system and with the standard thermoplastic mask were analyzed. RESULTS: CBCT scan results of the model group showed that the mean of linear error of three directions [superior-inferior (SI), lateral (LAT), and anterior-posterior (AP)] was 0.710 ± 0.676 mm, 0.817 ± 0.687 mm, and 0.710 ± 0.685 mm, respectively. The corresponding PTV was 1.23 mm, 1.26 mm, and 1.36 mm. The differences between the 3D images and the planned CT images were significant (p < 0.001). CONCLUSION: The Fraxion radiotherapy system can not only improve the positioning accuracy and reduce positioning errors but also narrow the PTV margin and reduce the radiated volume of normal tissue.

Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis.

Altered transforming growth factor (TGF)-ß expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-ß in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-ß1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-ß1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-ß1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-ß1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-ß1 overexpression was no longer evident. Therefore, overexpression of TGF-ß1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia.

Nonlinear wave propagation in an asymmetric converging Y junction.

Nonlinear wave propagation in an asymmetric converging Y junction, which consists of a nonlinear cladding, a linear film, and a linear substrate, is studied. The nonlinear dispersion curves of the successive sections of the Y junction are calculated to be used to illustrate the evolutions of the eigenmodes. The field incident from the nonlinear thinner branch can evolve into the symmetric mode of the stem with a high coupling efficiency. An insertion coupler for a time-multiplexed loop is suggested.

Nonlinear photonic switching by using the spatial soliton collision.

We introduce a novel device for optical switching by using the position shift of the spatial soliton after collision. The device is a one-to-three switching device controlled by two control beams. For the optimum signal power, the transmission efficiency is above 95%. The wave propagation in the structure and the transmission efficiency as a function of input signal power are shown and discussed.