Identification and validation of mutual hub genes in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated usual interstitial pneumonia.

Objectives: The study aims at exploring common hub genes and pathways in idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) through integrated bioinformatics analyses. Methods: The GSE199152 dataset containing lung tissue samples from IPF and RA-UIP patients was acquired from the Gene Expression Omnibus (GEO) database. The identification of overlapping differentially expressed genes (DEGs) in IPF and RA-UIP was carried out through R language. Protein-protein interaction (PPI) network analysis and module analysis were applied to filter mutual hub genes in the two diseases. Enrichment analyses were also conducted to analyze the possible biological functions and pathways of the overlapped DEGs and hub genes. The diagnostic value of key genes was assessed with R language, and the expressions of these genes in pulmonary cells of IPF and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients were analyzed with single cell RNA-sequencing (scRNA-seq) datasets. The expression levels of hub genes were validated in blood samples from patients, specimens of human lung fibroblasts, lung tissue samples from mice, as well as external GEO datasets. Results: Four common hub genes (THBS2, TIMP1, POSTN, and CD19) were screened. Enrichment analyses showed that the abnormal expressions of DEGs and hub genes may be connected with the onset of IPF and RA-UIP by regulating the progression of fibrosis. ScRNA-seq analyses illustrated that for both IPF and RA-ILD patients, THBS2, TIMP1, and POSTN were mainly expressed in lung fibroblasts, while CD19 was uniquely high-expressed in B cells. The qRT-PCR and immunohistochemistry (IHC) results verified that the expression levels of hub genes were mostly in accordance with the findings obtained from the bioinformatics analyses. Conclusion: Though IPF and RA-UIP are distinct diseases, they may to some extent have mutual pathogenesis in the development of fibrosis. THBS2, TIMP1, POSTN, and CD19 may be the potential biomarkers of IPF and RA-UIP, and intervention on related pathways of these genes could offer new strategies for the precision treatment of IPF and RA-UIP.

Screening and validation of differentially expressed genes in polymyositis.

Background: Polymyositis (PM), a prevalent inflammatory myopathy, currently lacks defined pathogenic mechanism. To illuminate its pathogenesis, we integrated bioinformatics and clinical specimens to examine potential aberrant gene expression patterns and their localization. Methods: We obtained GSE128470 and GSE3112 dataset from the Gene Expression Omnibus, performed Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis using CiberSort, identified differentially expressed genes with Limma, conducted functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, constructed a Protein-Protein Interaction network, and identified hub genes using Cytoscape. ROC analysis evaluated hub gene diagnostic accuracy for PM, validated their expression levels with clinical specimens. Results: DEG analysis revealed 51 upregulated and 779 downregulated genes. Gene Ontology (GO) analysis implicated Type I interferon (IFN-Ⅰ) signaling, while KEGG pointed to cell adhesion molecule activation and oxidative phosphorylation inhibition. Protein-Protein Interaction (PPI) analysis identified 8 diagnosffftic hub genes. Clinical samples confirmed their upregulation in PM, especially IRF1 and IRF9 between muscle fibers. Different immune cell infiltrations were observed in PM patients versus controls. Conclusions: Our study explores potential pathogenic factors, diagnostic markers, and immune cells in PM, with a focus on verifying IRF1 and IRF9 upregulation in the IFN-I signaling pathway. These findings bear significance for PM diagnosis and treatment.

Facile synthesis of NiFe2O4-based nanoblocks for low-temperature detection of trace n-butanol.

Fe2O3-loaded NiFe2O4 nanoblocks were successfully developed under a straightforward one-step hydrothermal synthesis method, aiming to detect trace amounts of n-butanol at the parts per billion (ppb) concentration range. The synthesized samples were comprehensively characterized using various techniques, including XRD, SEM, XPS, TEM and SAED. At a tantalizingly low temperature of 130 °C, the Ni/Fe-2 gas sensor demonstrated the optimum response (Ra/Rg = 29.747 @ 10 ppm) to n-butanol. Furthermore, Ni/Fe-2 sensor exhibited remarkable stability and reproducibility and an ultra-low detection limit. The enhanced gas sensitivity was primarily due to the assembly of Ni/Fe-2 nanoblocks from differently sized nanospheres, which exhibited a rich surface porosity conducive to gas adsorption. Besides, the formation of heterojunctions and the augmentation of oxygen vacancy content are also conducive to enhancing gas sensing capabilities. The Ni/Fe-2 sensor is expected to successfully detect trace amounts of n-butanol.

CD4+LAG3+T cells are decreased in SSc-ILD and affect fibroblast mesenchymal transition by TGF-ß3.

Pulmonary fibrosis frequently occurs in rheumatic conditions, particularly systemic sclerosis-associated interstitial lung disease (SSc-ILD). The pathology involves cell transformation into interstitial structures and collagen accumulation. CD4+LAG3+T cells, known for immune inhibition, are relevant in autoimmunity. This study investigates CD4+LAG3+T cells in SSc-ILD. Clinical analysis revealed a correlation between CD4+LAG3+T cells and interleukin-6 (IL-6) and erythrocyte sedimentation rate (ESR). Using primary human lung fibroblasts (pHLFs) and murine bone marrow-derived macrophages (BMDMs), we showed that CD4+LAG3+T cells secreted TGF-ß3 inhibits TGF-ß1-induced mesenchymal transformation, modulates cellular function, and reduces collagen release. In mouse models, CD4+LAG3+T cells exhibited potential in alleviating bleomycin-induced pulmonary fibrosis. This study emphasizes CD4+LAG3+T cells' therapeutic promise against fibrosis and proposes their role as biomarkers.

Application of Familial Y-STR Haplotype Mismatch Tolerance in Genealogy Inference.

OBJECTIVES: To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage. METHODS: Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed. RESULTS: Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6. CONCLUSIONS: Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.

Identification of Human Body Fluid Stains and Non-Biological Stains by Three-Dimensional Fluorescence Spectroscopy.

OBJECTIVES: To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy. METHODS: The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types. RESULTS: According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy. CONCLUSIONS: Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.

Application of transcriptome in time analysis and donor characterization in blood samples.

As an effective supplement to the current forensic DNA typing and one of the research hotpots in forensic science, the in-depth mining and characterization of biological evidence can provide rich and reliable clues for case investigation. In this study, the time-dependent variations of transcriptome were confirmed in in vitro blood samples within 0-168 days and a random forest model was established to realize the classification of blood samples with different TSD (time since deposition). Meanwhile, significant differences were observed in the transcripts of blood samples with different smoking habits and genders within a certain time period. HLA-DRB1, HLA-DQB1 and HLA-DQA2 were identified as markers for smoking habit identification, while the transcripts for RPS4Y1 and EIF1AY from the non-recombining region of the Y chromosome (NRY) were identified as markers for male sex identification. Thus, this study provides a theoretical foundation and experimental strategy for establishing a transcriptome-based method for characterizing blood sample retention time and donor characteristics in the field of forensic investigation.

Anatomical distance affects functional connectivity at rest in medicine-free obsessive-compulsive disorder.

BACKGROUND: Brain functional abnormalities at rest have been observed in obsessive-compulsive disorder (OCD). However, whether and how anatomical distance influences functional connectivity (FC) at rest is ambiguous in OCD. METHODS: Using resting-state functional magnetic resonance imaging data, we calculated the FC of each voxel in the whole-brain and divided FC into short- and long-range FCs in 40 medicine-free patients with OCD and 40 healthy controls (HCs). A support vector machine (SVM) was used to determine whether the altered short- and long-range FCs could be utilized to distinguish OCD from HCs. RESULTS: Patients had lower short-range positive FC (spFC) and long-range positive FC (lpFC) in the left precentral/postcentral gyrus (t = -5.57 and -5.43; P < 0.05, GRF corrected) and higher lpFC in the right thalamus/caudate, left thalamus, left inferior parietal lobule (IPL) and left cerebellum CrusI/VI (t = 4.59, 4.61, 4.41, and 5.93; P < 0.05, GRF corrected). Furthermore, lower spFC in the left precentral/postcentral gyrus might be used to distinguish OCD from HCs with an accuracy of 80.77%, a specificity of 81.58%, and a sensitivity of 80.00%. CONCLUSION: These findings highlight that anatomical distance has an effect on the whole-brain FC patterns at rest in OCD. Meanwhile, lower spFC in the left precentral/postcentral gyrus might be applied in distinguishing OCD from HCs.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging and 3D-ASL to Assess the Value of Ki-67 Labeling Index and Grade in Glioma.

Objective: To determine the proportion of intravoxel incoherent motion diffusion-weighted images (IVIM-DWI) and three-dimensional arterial circulation markers (3D-ASL) in Ki-67 labeling index (Ki-67 LI) and glioma grading. Methods: According to the classification of diseases of the central nervous system dealt with by WHO in 2007, patients with stage II glioma were classified as low (n = 20) and patients with stages III-IV were divided into higher levels (n = 22). Prior to surgery, brain MRI, IVIM-DWI, and 3D-ASL were performed in all patients, and the actual water molecular diffusion coefficient (D), microcirculation coefficient (D∗), blood flow fraction (f), and cerebral blood flow (CBF) were measured. A rank sum (Mann-Whitney U test) was used to compare the four upper and lower level Ki-67 LI measurements. Spearman's method is used to identify the relationship between 4 groups of quantification and Ki-67 LI. Reciprocal grafting (ROC) curves were used to measure the diagnosis of four groups of glioma grading defects. Results: There were significant differences in D, D∗, f, and CBF between the solid region of the tumor and the normal white matter contralateral to it (P < 0.05). The significant differences of rD, rD∗, rf, and rCBF were shown between patients with low-grade glioma and high-grade glioma (P < 0.05). Ki-67 LI was found to have negative correlation with rD (r = 00.693, P < 0.001) and rf (r = 00.539, P < 0.001), but similarly correlated with rCBF (r = 0.665, P < 0.001) in patients with glioma. Recipient efficacy for predicting advanced and secondary glioma from rD, rf, rD∗, rCBF, and Ki-67 LI raises AUCs of 0.819, 0.747, 0.719, 0.836, and 0.907, respectively. Conclusion: IVIM-DWI has good application value for preoperative grading of glioma.

Predictive Value of MRI with Serum Lectin-Reactive Alpha-Fetoprotein for Liver Cancer Recurrence after Percutaneous Radiofrequency Ablation.

Objective: To explore the predictive value of magnetic resonance imaging (MRI) with serum lectin-reactive alpha-fetoprotein (AFP-L3) for liver cancer recurrence after percutaneous radiofrequency ablation (RFA). Methods: This study included 94 liver cancer patients admitted for RFA treatment and 82 healthy subjects. MRI was performed to record the apparent diffusion coefficient (ADC). The serum concentrations of AFP-L3 were quantified in all participants. The correlation of the AFP-L3 serum level and ADC value with clinical efficacy following RFA was analyzed. Moreover, the prognostic factors affecting liver cancer recurrence were analyzed, as well as the predictive effect of the ADC value and AFP-L3 on liver cancer recurrence. Results: The serum AFP-L3 level was higher in liver cancer patients than the healthy controls with a lower ADC value. Besides, the patients with tumor residuals had lower ADC values and higher serum AFP-L3 levels than those with complete ablated tumor. The combined detection of the ADC value and serum AFP-L3 level had a sensitivity of 87.50% and a specificity of 87.18% for diagnosing complete ablation after RFA treatment. The number of tumor nodules, tumor diameter, AFP, AFP-L3, and the presence of liver cirrhosis are all independent risk factors for liver cancer recurrence within one year. Meanwhile, the combined detection of the ADC value and serum AFP-L3 level had a good predictive effect on liver cancer recurrence with the sensitivity of 92.86% and a specificity of 69.62%. Conclusion: The ADC values combined with serum AFP-L3 detection had good predictive effects on complete ablation and recurrence of liver cancer after RFA treatment.

Altered Regional Activity and Network Homogeneity within the Fronto-Limbic Network at Rest in Medicine-Free Obsessive-Compulsive Disorder.

Functional abnormalities in brain areas within the fronto-limbic network have been widely reported in obsessive-compulsive disorder (OCD). However, region- and network-level brain activities of the fronto-limbic network at rest have not been simultaneously investigated in OCD. In this study, 40 medicine-free and non-comorbidity patients with OCD and 38 age-, education-, and gender-matched healthy controls (HCs) underwent a resting-state functional magnetic-resonance-imaging scan. Fractional amplitude of low-frequency fluctuations (fALFF), network homogeneity (NH), and support vector machine were used to analyze the data. Patients with OCD showed increased fALFF in the right orbital frontal cortex (OFC), increased NH in the left OFC, and decreased NH in the right putamen. Decreased NH of the right putamen was negatively correlated with the Y-BOCS total and compulsive behavior scores. Furthermore, a combination of NH in the left OFC and right putamen could be applied to differentiate OCD from HCs with optimum specificity and sensitivity. The current findings emphasize the crucial role of the fronto-limbic network in the etiology of OCD.

Promoting the reduction of CO2 to formate and formaldehyde via gas-liquid interface dielectric barrier discharge using a Zn0.5Cd0.5S/CoP/multiwalled carbon nanotubes catalyst.

A Zn0.5Cd0.5S (ZCS) solid solution was prepared using a hydrothermal method, in which CoP nanowires were added as a co-catalyst and co-deposited with multiwalled carbon nanotubes (MWNTs) on sponge to prepare a series of ZCS/CoP/MWNTs/sponge electrodes. The microstructures of catalysts were analyzed to confirm ZCS and CoP were successfully loaded in MWNTs/sponge. The CO2 reduction products (formate and formaldehyde) produced via dielectric barrier discharge (DBD) using the different catalysts proved that the introduction of the CoP nanowires co-catalyst can enhance the catalytic activity of ZCS/MWNTs/sponge in the DBD system. Using 10% CoP and a ZCS/CoP concentration of 2.5 g·L-1, the resulting ZCS/CoP/MWNTs/sponge catalyst exhibited the best catalytic of CO2 reduction ability toward formate (7894.6 µmol·L-1) and formaldehyde (308.5 µmol·L-1) after 60 min of discharge, respectively. The proposed DBD catalytic mechanism for the reduction of CO2 was analyzed according to the Tafel slope, density functional theory calculations, photocurrent density and plasma reaction process. Furthermore, the application of the DBD catalytic technology for CO2 capture and reduction was shown to be efficient in a seawater system, and as such, it could be useful for marine CO2 storage and conversion.

Involvement of MiRNA-211-5p and Arhgap11a Interaction During Osteogenic Differentiation of MC3T3-E1 Cells.

Objective: MicroRNAs (miRNAs) are well-recognized for their abilities to regulate gene expression post-transcriptionally in plants and animals. Recently, miRNA-messenger RNA (mRNA) regulatory relationships have been confirmed during biological processes, including osteogenic differentiation. This study aimed to find out more candidate miRNA-mRNA pairs involved in the osteogenic differentiation of MC3T3-E1 cells. Methods: An MC3T3-E1-based microarray dataset (accessioned as GSE46400) downloaded from the Gene Expression Omnibus included MC3T3-E1 cells with or without 14-day osteoblast differentiation osteoblast induction. Multiple miRNA-mRNA prediction databases were searched by differentially expressed genes (DEGs) to obtain pairs of a miRNA-DEG regulatory network. The MC3T3-E1 cells were cultured and incubated in the osteogenic differentiation medium for 14 days. The expressions of candidate miRNAs and mRNAs were determined by real-time quantitative PCR(RT-qPCR) in MC3T3-E1 cells. The miRNA-mRNA interactions were verified by dual-luciferase reporter gene assays and experiments using mimics miRNA or their inhibitors. Results: We identified 715 upregulated DEGs and 603 downregulated DEGs between MC3T3-E1 cells with and without osteoblast induction by analyzing the raw data of the GSE46400 dataset. There were 7 overlapped miRNA-mRNA pairs identified during osteogenic differentiation of MC3T3-E1 cells, including mmu-miR-204-5p-Arhgap11a, mmu-miR-211-5p-Arhgap11a, mmu-miR-24-3p-H2afx, mmu-miR-3470b-Chek2, mmu-miR-3470b-Dlgap5, mmu-miR-466b-3p-Chek1, and mmu-miR-466c-3p-Chek1. The Arhgap11a, H2afx, Chek2, Dlgap5, and Chek1 were hub genes downregulated in MC3T3-E1 cells after osteogenic differentiation, verified by RT-qPCR results. The RT-qPCR also determined declined expressions of miR-204-5p and miR-24-3p concomitant with elevated expressions of miR-211-5p, miR-3470b, miR-466b-3p, and miR-466c-3p in the MC3T3-E1 cells, with osteoblast induction compared with undifferentiated MC3T3-E1 cells. Dual-luciferase reporter gene assays demonstrated Arhgap11a as the target of miR-211-5p. MiR-211-5p upregulation by its mimic increased Arhgap11a expression in MC3T3-E1 cells. Conclusion: Our study characterizes miR-211-5p targeting Arhgap11a promotes the osteogenic differentiation of MC3T3-E1 cells, which provides novel targets to promote the osteogenesis process during bone repair.

A convolutional neural network-based COVID-19 detection method using chest CT images.

Background: High-throughput population screening for the novel coronavirus disease (COVID-19) is critical to controlling disease transmission. Convolutional neural networks (CNNs) are a cutting-edge technology in the field of computer vision and may prove more effective than humans in medical diagnosis based on computed tomography (CT) images. Chest CT images can show pulmonary abnormalities in patients with COVID-19. Methods: In this study, CT image preprocessing are firstly performed using fuzzy c-means (FCM) algorithm to extracted the region of the pulmonary parenchyma. Through multiscale transformation, the preprocessed image is subjected to multi scale transformation and RGB (red, green, blue) space construction. After then, the performances of GoogLeNet and ResNet, as the most advanced CNN architectures, were compared in COVID-19 detection. In addition, transfer learning (TL) was employed to solve overfitting problems caused by limited CT samples. Finally, the performance of the models were evaluated and compared using the accuracy, recall rate, and F1 score. Results: Our results showed that the ResNet-50 method based on TL (ResNet-50-TL) obtained the highest diagnostic accuracy, with a rate of 82.7% and a recall rate of 79.1% for COVID-19. These results showed that applying deep learning technology to COVID-19 screening based on chest CT images is a very promising approach. This study inspired us to work towards developing an automatic diagnostic system that can quickly and accurately screen large numbers of people with COVID-19. Conclusions: We tested a deep learning algorithm to accurately detect COVID-19 and differentiate between healthy control samples, COVID-19 samples, and common pneumonia samples. We found that TL can significantly increase accuracy when the sample size is limited.

Fat content in lumbar paravertebral muscles: Quantitative and qualitative analysis using dual-energy CT in correlation to MR imaging.

PURPOSE: This study aims to assess the diagnostic performance of dual-energy computed tomography (DECT) on lumbar paravertebral muscles fat infiltration (PMFI) in participants with low back pain (LBP). METHOD: In this prospective study, 21 participants with LBP were performed with noncontrast DECT scans within 1 week after magnetic resonance (MR) examinations. The assessment was based on the selected region of interest obtained from the paravertebral L1/L2-L5/S1 muscle. On visual evaluation, PMFI was assessed at DECT virtual monoenergetic images (80 keV) with Goutallier classification system using MR results as a reference. Quantitative parameters fat fraction, CT number, ΔCT number (difference of CT number at 140 and 80 keV), and optimal cutoff values above the indicators between MR adjacent grades were measured. RESULTS: In this study, 582 ROIs from 21 participants (mean age, 60 ± 16 years old; 15 females) were evaluated. Sensitivity, specificity, and accuracy of readers 1 and 2 at severe grade (grades 3 and 4) were 67% and 85% (22 and 28 of 33), 99% and 99% (159 and 160 of 161), and 93% and 97% (181 and 188 of 194), respectively. Interobserver reliability was high with κ = 0.85 (p < 0.001). For DECT quantification parameters, significance was all represented between five grades (all p < 0.01). The area under the curve of indicators for discrimination between severe (grades 3 and 4) and normal and moderate (grades 0, 1, and 2) grades were > 0.80 (p < 0.001). CONCLUSIONS: DECT was a promising qualitative and quantitative imaging technique to assess lumbar PMFI in participants with LBP and could provide accurate quantification for different fat infiltration (FI) degrees. Moreover, visual DECT assessment could excellently distinguish severe from normal and moderate FI of MR grades.

Rescued from desperation: adult-onset Still's disease with life-threatening interstitial lung disease and macrophage activation : Successful treatment by Tocilizumab.

This article presents a case of fulminant interstitial lung disease (ILD) with macrophage activation syndrome (MAS) as a rare complication of adult-onset Still's disease in a 43-year-old male patient. Initial presentation showed severe ILD. Early treatment focused on high-dose corticosteroids; however, disease remission could not be achieved. After an additional inflammatory focus and underlying malignancy were excluded, the triad of pancytopenia, fever, and high ferritin levels indicated MAS; bone marrow biopsy confirmed secondary hemophagocytic histiocytosis. Treatment with tocilizumab induced fast and effective therapeutic success.

Tofacitinib for the treatment of rheumatoid arthritis: a real-world study in China.

Tofacitinib has only been available in China for 2 years to treat rheumatoid arthritis (RA). Our purpose was to compare real-world effectiveness of tofacitinib with that of disease-modifying anti-rheumatic drugs (DMARDs) in Chinese patients with RA. The records of patients with RA treated at Guangdong Provincial People's Hospital between July 2017 and September 2019 were retrospectively reviewed. Patients were divided into those treated with tofacitinib, biological DMARDs (bDMARDs), and conventional synthetic DMARDs (csDMARDs). Clinical disease activity index (CDAI), simplified disease activity index (SDAI), health assessment questionnaire-disability index (HAQ-DI), visual analog scale (VAS) pain score, patient global assessment of disease activity (PtGA), physician global assessment of disease activity (PhGA), and swollen joint and tender joint count were compared among the groups up to 12 months of treatment. A total of 150 patients were included: 63 were treated with tofacitinib, 48 with bDMARDs, and 39 with csDMARDs. Tofacitinib was first-line treatment in 26.98% of patients, second-line treatment in 49.21%, and third-line treatment in 26.98%. Patients in the tofacitinib group had significantly higher disease duration (6.11 ± 6.97 years) than those in the other groups. All disease indices in the three groups decreased with time, indicating improvement of symptoms, with no differences among the groups at 12 months. Tofacitinib appeared to improve symptoms more rapidly than other treatments; however, differences in disease indices were not significant. This real-world study suggests that tofacitinib is rapidly effective and that the effects are sustained after 12 months in Chinese patients with RA.

Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder.

Background: Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear. Methods: A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier. Results: Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%. Conclusion: Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.

Decreased Nucleus Accumbens Connectivity at Rest in Medication-Free Patients with Obsessive-Compulsive Disorder.

Background: Patients with obsessive-compulsive disorder (OCD) experience deficiencies in reward processing. The investigation of the reward circuit and its essential connectivity may further clarify the pathogenesis of OCD. Methods: The current research was designed to analyze the nucleus accumbens (NAc) functional connectivity at rest in medicine-free patients with OCD. Forty medication-free patients and 38 gender-, education-, and age-matched healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. Seed-based functional connectivity (FC) was used to analyze the data. LIBSVM (library for support vector machines) was designed to identify whether altered FC could be applied to differentiate OCD. Results: Patients with OCD showed remarkably decreased FC values between the left NAc and the bilateral orbitofrontal cortex (OFC) and bilateral medial prefrontal cortex (MPFC) and between the right NAc and the left OFC at rest in the reward circuit. Moreover, decreased left NAc-bilateral MPFC connectivity can be deemed as a potential biomarker to differentiate OCD from HCs with a sensitivity of 80.00% and a specificity of 76.32%. Conclusion: The current results emphasize the importance of the reward circuit in the pathogenesis of OCD.

Disrupted Asymmetry of Inter- and Intra-Hemispheric Functional Connectivity at Rest in Medication-Free Obsessive-Compulsive Disorder.

Disrupted functional asymmetry of cerebral hemispheres may be altered in patients with obsessive-compulsive disorder (OCD). However, little is known about whether anomalous brain asymmetries originate from inter- and/or intra-hemispheric functional connectivity (FC) at rest in OCD. In this study, resting-state functional magnetic resonance imaging was applied to 40 medication-free patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs). Data were analyzed using the parameter of asymmetry (PAS) and support vector machine methods. Patients with OCD showed significantly increased PAS in the left posterior cingulate cortex, left precentral gyrus/postcentral gyrus, and right inferior occipital gyrus and decreased PAS in the left dorsolateral prefrontal cortex (DLPFC), bilateral middle cingulate cortex (MCC), left inferior parietal lobule, and left cerebellum Crus I. A negative correlation was found between decreased PAS in the left DLPFC and Yale-Brown Obsessive-compulsive Scale compulsive behavior scores in the patients. Furthermore, decreased PAS in the bilateral MCC could be used to distinguish OCD from HCs with a sensitivity of 87.50%, an accuracy of 88.46%, and a specificity of 89.47%. These results highlighted the contribution of disrupted asymmetry of intra-hemispheric FC within and outside the cortico-striato-thalamocortical circuits at rest in the pathophysiology of OCD, and reduced intra-hemispheric FC in the bilateral MCC may serve as a potential biomarker to classify individuals with OCD from HCs.