Global Phosphoproteomics Unveils Kinase-Regulated Networks in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune complex deposition in multiple organs. Despite the severe symptoms caused by it, the underlying mechanisms of SLE, especially phosphorylation-dependent regulatory networks remain elusive. Herein, by combining high-throughput phosphoproteomics with bioinformatics approaches, we established the global phosphoproteome landscape of the peripheral blood mononuclear cells from a large number of SLE patients, including the remission stage (SLE_S), active stage (SLE_A), rheumatoid arthritis, and healthy controls, and thus a deep mechanistic insight into SLE signaling mechanism was yielded. Phosphorylation upregulation was preferentially in patients with SLE (SLE_S and SLE_A) compared with healthy controls and rheumatoid arthritis populations, resulting in an atypical enrichment in cell adhesion and migration signatures. Several specifically upregulated phosphosites were identified, and the leukocyte transendothelial migration pathway was enriched in the SLE_A group by expression pattern clustering analysis. Phosphosites identified by 4D-label-free quantification unveiled key kinases and kinase-regulated networks in SLE, then further validated by parallel reaction monitoring. Some of these validated phosphosites including vinculin S275, vinculin S579 and transforming growth factor beta-1-induced transcript 1 S68, primarily were phosphorylation of Actin Cytoskeleton -related proteins. Some predicted kinases including MAP3K7, TBK1, IKKß, and GSK3ß, were validated by Western blot using kinases phosphorylation sites-specific antibodies. Taken together, the study has yielded fundamental insights into the phosphosites, kinases, and kinase-regulated networks in SLE. The map of the global phosphoproteomics enables further understanding of this disease and will provide great help for seeking more potential therapeutic targets for SLE.

[Bioinformatics analysis and systematic review of key genes and therapeutic traditional Chinese medicine of ulcerative colitis active stage].

Data GSE75214 and GSE48959 that contained ulcerative colitis(UC) in the active stage was download from GEO database. Differential genes of UC in the active phase were obtained by using adjusted P<0.05 and |log_2 FC|≥1.5, which was the screening criteria. PPI analysis was performed in the STRING database, and GO and KEGG pathway analysis was performed in DAVID database. Cytoscape was used to visualize differential genes, and calculate key genes in the active phase. Coremine Medical was used to analyze and systematically evaluate traditional Chinese medicines for treating key genes. Finally, 139 differentially expressed genes in the active phase were screened out, which included the 109 up-regulated genes and 30 down-regulated genes. DAVID analyzed that the biology and pathways of these differential genes were mainly concentrated in inflammatory response, immune response, chemokine activity, TNF pathway, NF-κB pathway, and Toll-like receptor pathway. Cytoscape software calculated that IL-6, CXCL8, IL-1ß, MMP9, CXCL1, ICAM1, CXCL10, TIMP1, PTGS2 and CXCL9 were the key genes of UC in the active phase. According to Coremine Medical analysis, traditional Chinese medicines for UC in the active stage included Curcumae Longae Rhizoma, Scutellariae Radix, Curcumae Radix had clearing heat clearing damp, reducing fire and detoxifying effects, which was in line with the pathogenesis of UC active stage, and was often used in clinical treatment of dampness-heat diarrhea. Therefore, Huangqin Decoction, which Scutellariae Radix was the principal drug, was selected for systematic evaluation. The evaluation showed that Scutellariae Radix was superior to Western medicine in terms of improving clinical efficiency, reducing inflammatory factors and immunoglobulin levels, with statistically significant differences and fewer adverse reactions. This study provided a new idea for further research on the pathogenesis of UC in the active phase by analyzing the genes and their mechanism of action, and the systematic evaluation of Chinese medicine for the treatment of UC active stage provided a basis for the clinical prevention and treatment of UC by Chinese medicine.

Labor progress indices and dynamics of the individual uterine contraction during the active stage of labor.

AIM: To obtain and study new data on the dynamics of the labor process and to develop a contraction-based index of labor progress. METHODS: This study was carried out at the Delivery Room, Department of Obstetrics and Gynecology, Western Galilee Hospital, Nahariya, Israel, using a new device (Birth Track). We continuously monitored cervical dilatation (CD) and head descent (HD) in 30 nulliparaous women during active labor with (augmented group) and without (study group) oxytocin augmentation. This led to the development and validation of progress indices based on features extracted from continuous monitoring. RESULTS: There were no significant differences between the average of each parameter in the study and augmented groups, except for HD velocity. Average HD velocity was faster in the study group. Linear regression analyses demonstrated that head station (HS) amplitude and Toco amplitude were the best parameters for predicting HD velocity in both groups. In the study group, average HD velocity was also significantly related to Toco rate and contraction efficiency. In the augmented group, only a weak correlation with Toco rate was seen, and no correlation with contraction efficiency. CONCLUSION: With the assistance of the Birth Track device, we can obtain continuous data on the labor process and indices to estimate the labor progress process without the use of vaginal (manual) examination.

Case Report: Exacerbation after fat grafting in patients with active localized scleroderma.

Background: The application of autologous fat transplantation in facial lesions of patients with localized scleroderma (LoS) has been reported in recent years. Objective: The authors report a case of worsening of active localized scleroderma after autologous fat transplantation. Methods: A man presented with neck and facial skin atrophy and pigmentation with a history of LoS. Appearing 1.5 years ago, the lesion had progressively grown in size and shape. Consent was obtained after the patient was informed of the possible surgical risks during the active phase of the disease. He underwent autologous fat grafting into the right cheek with about 30 ml Coleman fat graft. Results: Skin dyspigmentation and atrophy progressively deteriorated 1 month into therapy, with slightly increased erythema and enlargement of the lesion. Six months after the therapy, the localized scleroderma-related score worsened. Limitations: There are different factors, such as that systemic medications could affect the treatment of localized scleroderma by autologous fat transplantation. Meanwhile, considering the limitation of the 6-month follow-up period, obtaining long-term follow-up data is necessary to evaluate sustained outcomes and potential complications. Conclusion: More clinical research is needed to determine the time interval between disease inactivity and the application of any surgical procedures to avoid reactivation.

Diagnostic Value of 3.0 T Magnetic Resonance Imaging in Active Crohn's Disease.

BACKGROUND: Magnetic resonance enteroclysis (MRE) has been widely applied to diagnose Crohn's disease (CD). Magnetic resonance (MR) at 3.0 T improves signal-to-noise ratio (SNR), shortens image acquisition time, and shows more advantages. OBJECTIVE: This study aimed to retrospectively analyze the diagnostic value of 3.0 T MR imaging for active CD. METHODS: 48 CD patients hospitalized in our hospital from January 2021 to December 2022 were selected as the study subjects. These 48 CD patients underwent both double-balloon enteroscopy and 3.0 T MRE. All patients' arterial phase signal, venous phase signal, bowel wall, and bowel lumen of MRE were observed to identify whether they suffered from active CD. Based on the results of enteroscopy, the number of true positives, true negatives, false negatives, and false positives diagnosed by MRE were screened; next, the diagnostic accuracy, sensitivity, and specificity of MRE in assessing active CD were calculated. RESULTS: Of the 48 patients, 39 were diagnosed with small bowel CD by MRE, which was not significantly different from the results of enteroscopy (P>0.05). According to MRE diagnostic results, the arterial phase predominantly presented high signal intensity, and the venous phase mainly presented low signal intensity or isointensity. Small bowel CD lesions were primarily characterized by bowel wall thickening, rare pneumatosis enhancement of the bowel wall, bowel lumen pneumatosis or dilatation, and rare strictures. Besides, MRE presented an accuracy of 93.75%, sensitivity of 97.37%, and specificity of 80.00% in diagnosing CD. CONCLUSION: 3.0 T MR imaging has diagnostic value for active CD and shows certain clinical application value.

Genome-wide analysis of long non-coding RNAs in shoot apical meristem and vascular cambium in Populus tomentosa.

Shoot apical and lateral meristems play essential roles in the formation and development of primary and secondary growth in plants. A delicate regulatory mechanism is needed to maintain homeostatic balance between the primary and secondary growth, as well as the self-renewal of meristems with the rate of cell division and differentiation of new meristems. However, little is known about the roles of long non-coding RNAs (lncRNAs) in the regulation of maintenance and differentiation of primary and secondary growth in Populus, especially in the cambium division and differentiation into secondary xylem. Here, 1298 lncRNAs were identified both in the apical meristem and vascular cambium, with 80 lncRNAs being expressed only in shoot apical meristem and 45 only in vascular cambium. There are 410 differentially expressed lncRNAs in shoot apical meristem and vascular cambium, among which 271 lncRNAs were up-regulated and 139 were down-regulated in cambium. The GO enrichment analysis revealed that differentially expressed lncRNAs mainly influenced the expression of lncRNAs related to the ribosome pathway, plant hormone signal pathway and photosynthesis pathway. The differentially expressed lncRNAs mainly target mRNA through cis-regulation in the vascular cambium. In addition, six key lncRNAs and also their significantly upregulated target genes were identified. Theses target genes are involved in plant secondary metabolites, cellulose and lignin synthesis, hormone and signal transduction. In addition, six key lncRNAs were identified, their significantly upregulated target genes are related to plant secondary metabolites, cellulose and lignin synthesis, hormone and signal transduction. Investigating lncRNA-mRNA interactions, we further found some genes that may be related to the development of vascular cambium, such as domain-containing transcription factors, cellulose synthesis genes, calcium dependent protein kinase 2, cytokinin receptor 1, glycosyl transferase and polyphenol oxidase. Our findings provide new insights into the lncRNA-mRNA networks in the development of vascular cambium of secondary growth in Populus.

Dynamics of the Salivary Microbiome During Different Phases of Crohn's Disease.

Crohn's disease is a chronic disorder that typically affects the gastrointestinal tract. The increased incidence in the recent years, especially in Asian countries, prompts for performing studies and gain newer insights into the etiology and pathogenesis of the disease. Among other causative factors, gut microbiome and its cross-talk with the salivary microbiome is a known factor that has a plausible role in the pathogenesis of Crohn's disease. The gut microbiome has been extensively studied, however, the salivary microbiome and its dynamics during different phases of this disease remain understudied. In this study, we obtained saliva samples from the patients during active and remission phases of the disease and compared them with control samples and highlighted the differences in taxonomic as well as predicted functional pathways among them. Our results indicated that the α and ß diversities were significantly lower during the active phase in contrast with remission phase and healthy samples. In general, Firmicutes were most abundant among the three sample groups, followed by Bacteroidetes and Proteobacteria. Genus level distribution highlighted Streptococcus, Neisseria, Prevotella, Haemophilus, and Veillonella as the five most abundant taxa. Differential abundance analysis of the three sample groups identified significant enrichment of 30 bacterial taxa in the active phase that included g_Prevotella, f_Prevotellaceae, and p_Bacteroidetes. Furthermore, remission phase and control also exhibited significant enrichment of 24 and 22 bacterial taxa, respectively. Eleven differentially abundant pathways were also identified, four were significantly enriched in healthy controls whereas other seven were significantly enriched in active phase of the disease. Several important pathways, such as ribosome biogenesis and Energy metabolism were depleted in the active phase. Our study has highlighted several taxa and functional categories that could be implicated with the onset of Crohn's disease and thus have the potential to serve as biomarkers of the active disease. However, these findings require further validation through functional studies in the future.

Immunotherapies application in active stage of systemic lupus erythematosus in pregnancy: A case report and review of literature.

BACKGROUND: Pregnancy in the setting of systemic lupus erythematosus can worsen the condition from the stable to active stage, with quality of life and fertility desire being particular concerns. Pregnancy in the active stage of systemic lupus erythematosus (ASLE), although rare and complicated to manage, can be treated favorably with immunotherapies ifs used properly. Here we report such a success case. CASE SUMMARY: A 31-year-old primigravida patient, diagnosed with SLE seven years ago, was induced ASLE after a cold at 21 + weeks. The patient's vital signs on presentation were normal. Her laboratory exam was remarkable for significant proteinuria, liver and renal dysfunction, and low C3 and C4 levels. Infectious work-up was negative. The patient was diagnosed with ASLE. She was given immunosuppressive agents (methylprednisolone, gamma globulin and azathioprine etc.) and plasma adsorption therapy, monitoring blood pressure every 8 h, fetal heart rate twice a day, and liver and renal function at least twice a week. Successful maternal and fetal outcomes are presented here. CONCLUSION: Child-bearing in ASLE has become more promising, even for this difficult case of ASLE with multiple organ damage. Thorough antepartum counseling, cautious maternal-fetal monitoring, and multi-organ function monitoring by multidisciplinary specialties are keys to favorable pregnancy outcomes.

[The differences of myringoplasty performed in active and inactive nflammatory stage].

Objective:Through comparing of simple underlay myringoplasty performed in active and inactive inflammatory stage of the chronic otitis media, to explore how the tympanic cavity inflammation affect the outcome of the myringoplasty.Method：Forty-six ears were enrolled in active inflammation group (group A,n=46), and 52 ears were enrolled in inactive inflammation group (group B,n=52). All the patients had received the simple underlay technique myringoplasty. The following-up with otoscope and auditory test had been done in post-operative 12 months.Result:There was no statistic difference of gender and age between two groups. The graft taken-up rate of the group A was 87,0%, that of group B was 90,4%, and there was no statistic difference between two groups(P>0.05).There was no statistic difference of auditory threshold in pre-operative period(P>0.05) and the ABG closure in post-operative period(P>0.05)between two groups. The re-perforation rate of the tympanic membrane also has no difference between two groups(P>0.05).Conclusion：There is no difference of the underlay technique myringoplasty between the active inflammatory stage and inactive inflammatory stage. The active inflammatory condition of the tympanic cavity is not the contraindication of the myringoplasty.

CD8+CD28+/CD8+CD28- T cell equilibrium can predict the active stage for patients with inflammatory bowel disease.

BACKGROUND/AIM: The balance of blood CD8+CD28+/CD8+CD28- T cells has been verified to be vital for patients with ulcerative colitis (UC), but their role in inflammatory bowel disease (IBD) remains unknown. This investigation aimed to evaluate the efficiency of the balance in predicting the active stage in IBD patients. METHODS: Fifty-three IBD subjects, including 31 UC and 22 Crohn's disease (CD) patients, were enrolled, and their peripheral blood CD8+CD28+ and CD8+CD28- T cell levels were tested using flow cytometry. The risk factors related to prognosis were compared between UC and CD patients. A 1-year follow-up was performed for all the IBD patients, and the CD8+ T cells and their ratio were compared at the 3rd, 6th, 9th, and 12th months during follow-up. The sensitivity and specificity of the CD8+ T cell level and balance were analyzed through receiver operator characteristic (ROC) curves. The cumulative remission lasting rates (CRLRs) under the different factors were analyzed using the Kaplan-Meier method. RESULTS: Higher prescription rates of immunosuppressants, steroids, probiotics, and biological agents (BAs) were found in CD subjects in comparison to UC subjects (P=0.005, 0.024, 0.034, and 0.001), as was a higher active rate during follow-up (95.5% of CD patients vs 67.7% of UC patients, P=0.035). The CD8+CD28+ T cell level and the CD8+CD28+/CD8+CD28- T cell ratio were significantly higher in UC patients than in CD patients, but the reverse was true for CD8+CD28- T cells during follow-up at the 9th and 12th month (all P<0.05). The diagnostic models of the initial CD8+CD28+ and CD8+CD28- T cell numbers and the CD8+CD28+/CD8+CD28- T cell ratio in predicting the active stage were found to be significant, with areas under the curves (AUCs) of 0.883, 0.098, and 0.913 for UC subjects (with 95% CI: 0.709-0.940, 0.009-0.188, and 0.842-1.003; P=0.001, 0.00, and 0.000) and 0.812, 0.078, and 0.898 for CD subjects (with 95% CI: 0.683-0.957, 0.003-0.158, and 0.837-0.998; P=0.003, 0.00, and 0.000). The cut-off values showed that when the ratios were 1.30 for UC and 1.22 for CD patients, the best sensitivity and specificity were observed, with 91.6% and 89.0% for UC and 88.5% and 85.1% for CD, respectively. The CRLRs were significantly higher in female, non-BA-treated, non-surgical IBD subjects when compared to male, BA-treated, surgical subjects (P=0.031, 0.000, and 0.000). The number of CD8+CD28+ and CD8+CD28- T cells and the CD8+CD28+/CD8+CD28- T cell ratio were correlated with BA treatment and surgery (all P<0.05). CONCLUSION: The CD8+CD28+/CD8+CD28- T cell balance, expected to be a novel immunologic marker, presented a satisfactory efficiency with high sensitivity and specificity in predicting the active stage in UC and CD patients, and the balance was closely related to the use of BAs and surgery.

Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo

Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable.