Does Ulcerative Colitis Influence the Inter-individual Heterogeneity of the Human Intestinal Mucosal Microbiome?

The dysbiosis of the gut microbiome associated with ulcerative colitis (UC) has been extensively studied in recent years. However, the question of whether UC influences the spatial heterogeneity of the human gut mucosal microbiome has not been addressed. Spatial heterogeneity (specifically, the inter-individual heterogeneity in microbial species abundances) is one of the most important characterizations at both population and community scales, and can be assessed and interpreted by Taylor's power law (TPL) and its community-scale extensions (TPLEs). Due to the high mobility of microbes, it is difficult to investigate their spatial heterogeneity explicitly; however, TPLE offers an effective approach to implicitly analyze the microbial communities. Here, we investigated the influence of UC on the spatial heterogeneity of the gut microbiome with intestinal mucosal microbiome samples collected from 28 UC patients and healthy controls. Specifically, we applied Type-I TPLE for measuring community spatial heterogeneity and Type-III TPLE for measuring mixed-species population heterogeneity to evaluate the heterogeneity changes of the mucosal microbiome induced by UC at both the community and species scales. We further used permutation test to determine the possible differences between UC patients and healthy controls in heterogeneity scaling parameters. Results showed that UC did not significantly influence gut mucosal microbiome heterogeneity at either the community or mixed-species levels. These findings demonstrated significant resilience of the human gut microbiome and confirmed a prediction of TPLE: that the inter-subject heterogeneity scaling parameter of the gut microbiome is an intrinsic property to humans, invariant with UC disease.

Hippocampal Atrophy in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations.

This study was conducted to explore hippocampal structural changes and their possible associations with clinical characteristics, emotional status, and treatment regimens in patients with systemic lupus erythematosus (SLE) without major neuropsychiatric manifestations (non-NPSLE). Eighty-five non-NPSLE patients with normal conventional magnetic resonance imaging (MRI) and seventy-seven matched healthy control (HC) subjects were recruited. All participants underwent the standard high-resolution volumetric MRI. The bilateral hippocampal volume (HIPV) and hippocampal density (HIPD) were calculated, respectively, for each participant. We found that the bilateral HIPV and HIPD of the SLE patient group were significantly less than those of the HC group. The bilateral HIPV of female patients were significantly less than those of male patients. The SLE disease activity index (SLEDAI) was negatively correlated with the bilateral HIPV and the right HIPD. Urine protein quantity was negatively correlated with the bilateral HIPV and HIPD. Hydroxychloroquine (HCQ) showed a protective effect on right HIPV. In conclusion, we found that the early hippocampal atrophy could occur before obvious neuropsychiatric manifestations and might be associated with SLE disease activity and organ damages. Early detection and intervention of hippocampal damage might prevent the progression to NPSLE. More studies are needed to fully understand the underlying mechanisms of hippocampal atrophy in SLE.

Curculigoside exerts significant anti­arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF­κB signaling pathway.

The present study aimed to investigate the anti­arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6, IL­10, IL­12 and IL­17A. Furthermore, indices of the thymus and spleen were determined. The anti­proliferative effects of curculigoside were detected with Cell Counting kit­8 assays in rheumatoid arthritis­derived fibroblast­like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)­κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen­induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF­α, IL­1ß, IL­6, IL­10, IL­12 and IL­17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration­dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)­κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti­arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF­κB signaling pathway.

A Conscious Resting State fMRI Study in SLE Patients Without Major Neuropsychiatric Manifestations.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the main causes of death in patients with systemic lupus erythematosus (SLE). Signs and symptoms of NPSLE are heterogeneous, and it is hard to diagnose, and treat NPSLE patients in the early stage. We conducted this study to explore the possible brain activity changes using resting state functional magnetic resonance imaging (rs-fMRI) in SLE patients without major neuropsychiatric manifestations (non-NPSLE patients). We also tried to investigate the possible associations among brain activity, disease activity, depression, and anxiety. In our study, 118 non-NPSLE patients and 81 healthy controls (HC) were recruited. Rs-fMRI data were used to calculate the regional homogeneity (ReHo) in all participants. We found decreased ReHo values in the fusiform gyrus and thalamus and increased ReHo values in the parahippocampal gyrus and uncus. The disease activity was positively correlated with ReHo values of the cerebellum and negatively correlated with values in the frontal gyrus. Several brain areas showed correlations with depressive and anxiety statuses. These results suggested that abnormal brain activities might occur before NPSLE and might be the foundation of anxiety and depression symptoms. Early detection and proper treatment of brain dysfunction might prevent the progression to NPSLE. More studies are needed to understand the complicated underlying mechanisms.

Clinical Factors Associated with Brain Volume Reduction in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations.

The aim of the study was to find structural brain changes in systemic lupus erythematosus patients without major neuropsychiatric manifestations [non-neuropsychiatric systemic lupus erythematosus (non-NPSLE)] using quantitative magnetic resonance imaging (MRI) and possible associations with clinical characteristics. 89 non-NPSLE patients with normal conventional MRI and 84 healthy controls (HCs) were recruited. The whole brain gray matter volume (GMV) and white matter volume (WMV) were calculated for each individual. We found obvious GMV and WMV reduction in the systemic lupus erythematosus (SLE) group compared with HCs. Female patients showed significant reduction of GMV and WMV compared with male patients. Patients treated with immunosuppressive agents (ISA) showed less WMV reduction than those without. Cognitive impairment was the most common subclinical neuropsychiatric manifestation and had a prevalence of 46.1%. Association between WMV reduction with cognitive impairment was found. Thus, we concluded that structural brain atrophy could happen even before occurrence of obvious neuropsychiatric signs and symptoms and was associated with subclinical symptoms such as cognitive impairment. ISA treatment might have a protective effect on the brain atrophy. Early treatment might prevent the progressive damage to the brain. More studies are needed to fully understand the complicated underlying mechanisms of brain atrophy in SLE.

Link-Polymorphism of 5-HTT Promoter Region Is Associated with Autoantibodies in Patients with Systemic Lupus Erythematosus.

Serotonin transporter linked polymorphic region (5-HTTLPR) was reported to associate with depression in systemic lupus erythematosus (SLE) patients by our team. To explore whether 5-HTTLPR plays a role in the pathogenesis of SLE, we tested 138 SLE patients and 138 age and sex matched health controls (HCs) for 5-HTTLPR by polymerase chain reaction (PCR) and agarose gel electrophoresis. Interestingly, the results suggest that the frequencies of SS genotype and S allele in SLE patients with positive anti-Sm antibody and anti-U1RNP antibody were both significantly higher than the other genotypes and alleles. However, the frequencies of 5-HTTLPR genotypes and alleles were of no significant difference between SLE patients and HCs. This suggested that 5-HTTLPR was not a high-risk susceptible gene in SLE but might relate to SLE by affecting production of some autoantibodies, especially anti-Sm and anti-U1RNP antibody.

Depressive and Anxiety Disorders in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations.

Depressive and anxiety disorders are frequently observed in patients with Systemic Lupus Erythematosus (SLE). However, the underlying mechanisms are still unknown. We conducted this survey to understand the prevalence of depression and anxiety in SLE patients without major neuropsychiatric manifestations (non-NPSLE) and to explore the relationship between emotional disorders, symptoms, autoantibodies, disease activity, and treatments in SLE. 176 SLE patients were included, and SLE disease activity index (SLEDAI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) were recorded to evaluate their disease activity and emotional status. We found that depressive and anxiety disorders were common among SLE patients: 121 (68.8%) patients were in depression status while 14 (8.0%) patients could be diagnosed with depression. Accordingly, 101 (57.4%) were in anxiety status and 21 (11.9%) could be diagnosed with anxiety. Depression was associated with disease activity, and anxiety was associated with anti-P0 antibody, while both of them were associated with proteinuria. HAMA and HAMD scores were in strong positive correlation and they were independent risk factors of each other. We concluded that the high prevalence of depression and anxiety and the association between depression and SLE disease activity might reveal the covert damage of central nervous system in SLE. The role of anti-P0 antibody in SLE patients with emotional disorders warrants more researches.

Autoantibodies Affect Brain Density Reduction in Nonneuropsychiatric Systemic Lupus Erythematosus Patients.

This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE). Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD) and white matter (WMD) were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA), and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL) or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients.

[Clinical analysis of 29 patients with clinically amyopathic dermatomyositis].

OBJECTIVE: To explore the clinical features and prognosis of clinically amyopathic dermatomyositis (C-ADM). METHODS: The clinical data, including skin lesion, muscle involvement, and lung disease, of 29 patients with C-ADM, 6 males and 23 females with a male/female ratio of 1:3.83, aged 44 +/- 8, were analyzed. Skin biopsy was taken in 5 patients and lung HRCT was done in all the patients. RESULTS: The mean age at onset was (44 +/- 8) years. All patients presented with characteristic skin lesions such as Gottron's papulae (91.3%); heliotropic periorbital erythremia (75.9%); V-sign rash (37.9%); shawl-sign rash (24.1%); and periungual erythema and telangiectasias (20.7%). Gottron's papule was most commonly seen on the dorsal aspect of elbow (86.2%), proximal interphalangeal joints (58.6%), metacarpophalangeal joints (48.3%), patellae (23.8%), hip (20.7%), shoulder (13.8%), and ankle (9.5%). The cutaneous histopathologic pictures of these patients were all compatible with the skin lesions of dermatomyositis. Interstitial lung disease (ILD) was found by lung HRCT in 19 patients (65.5%). All patients received steroids combined with immunosuppressants, but rapidly progressive ILD happened to some of the patients and finally led to death due to respiratory failure in 5 of them. CONCLUSION: C-ADM is most commonly seen in the middle-aged women. ILD is the commonest respiratory problem arising in C-ADM patients and can be fatal, therefore should be properly treated.