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Objectives: Systemic sclerosis (SSc) is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. Transforming growth factor β (TGFβ) can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGFβ-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc., Methods: Genes related to TGFβ pathway were screened through bioinformatics analysis, and SSc phenotypes were verified in vivo and vitro. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing., Results: Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGFβ induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGFβ-mediated fibroblasts with up-regulation of CRISPLD2., Conclusion: CRISPLD2 was found increased reactivity in TGFβ induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGFβ induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In order to explore the huge impact of impaired immnue homeostasis on the occurrence and development of cutaneous squamous cell carcinoma (cSCC), and investigate characterization of the cellular components and their changes which is crucial to understanding the pathologic process of HPV-induced cSCC, we diagnosed and followed up on a very rare HPV-induced cSCC patient who progressed at a very fast rate and transferred to death quickly. We performed single-cell RNA sequencing (scRNA-seq) of 11 379 cells from the skin tissues of this patient with four different skin statuses after HPV infection. Immunofluorescence experiments were used for validation. scRNA-seq identified that CD52 + HLA-DOA - macrophages only existed in paracancerous cutaneous squamous cell carcinoma (pc-cSCC) and cSCC tissue. Besides, immune cells including CD8 + exhausted T cells and CD4 + regulatory T cells as well as matrix cells like MMP1 + , and MMP11 + fibroblasts were gradually increased. Meanwhile, COMP + ASPN + fibroblasts gradually decreased. Cell interaction analysis revealed enhancement in interactions between monocytes/macrophages, fibroblasts and tumour-specific keratinocytes. scRNA-seq was performed in HPV-induced cSCC for the first time, to explore the correlation between infection and tumour. It is the first time to study the development of tumours from different stages of infection in HPV-induced cSCC. In this study, the tumour itself and the tumour microenvironment were both analysed and explored. And it was validated in clinical samples from different patients. Our findings reveal the dynamic immnue homeostasis from normal skin to cSCC tissue, this alteration might drive HPV-induced cSCC., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Alternative splicing (AS) and intron retention (IR) implicated in multiple pathophysiological processes, have rarely been reported in systemic sclerosis (SSc)., Methods: We integrated bulk RNA-seq and 4D label-free mass spectrometry to perform a multi-omics analysis of AS and IR in SSc skin tissue and fibroblasts. RMATS and iREAD were used to identify AS and IR, which were validated by real-time PCR. Spearman correlation and the LASSO method were employed to assess correlations among clinical features, introns, splicing factors (regulators of AS) and proteins., Findings: AS profiles showed distinct alterations in SSc skin tissue, with the most pronounced changes occurring in IR. AS and IR were associated with total modified Rodnan skin score (mRSS) and local skin score. Upon TGF-β stimulation, fibroblasts exhibited significant alterations in IR profiles, affecting genes related to fibroblast proliferation and collagen fibril organization. A comprehensive integrated analysis of introns, exons, and proteome profiles revealed that IR exerted a negative impact on protein expression, with certain changes being under intronic control. RT-PCR confirmed the presence of intron and exon-derived sequences of CTTN, OGA, MED16 and PHYKPL. Additionally, notable changes were observed in the regulatory network of splicing factors in SSc skin tissues. These factors are also involved in fibrosis pathways and correlated with clinical features., Conclusion: Totally, abnormal AS, IR profiles and splicing factors were identified in SSc, altered IRs and splicing factors participated in fibrosis-related pathways. IR exerted a negative impact on protein expression in TGF-β-stimulated fibroblasts. Clarification of the IR mechanisms will provide new insights into the pathophysiology of SSc., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Diabetes peripheral neuropathy (DPN) is mainly treated with diabetes as a whole, and there is no targeted treatment. Some studies have reported that adjuvant hyperbaric oxygen therapy (HBOT) for DPN has achieved a good effect, our study aimed to evaluate the clinical efficacy and safety of HBOT for DPN and provide reference for the clinic by using a systematic review and meta-analysis., Methods: A comprehensive search was conducted across several databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet Database, Chinese BioMedical Database, China Scientific Journal Database, and Wanfang Database, for relevant randomized controlled trials published before July 2022. The population, intervention, comparison, outcomes, study design criteria were used to guide the selection of studies. Meta-analysis was performed using RevMan 5.4 and STATA 14.0, with odds ratios and mean differences along with 95% confidence intervals serving as measures of effect size., Results: Fourteen randomized controlled trials were included in the final analysis, comprising 675 patients in the HBOT group and 648 in the standard therapy (ST) group. The HBOT group demonstrated a significantly higher effective treatment rate compared to the ST group (P < .001). Additionally, the HBOT group showed significant improvements in motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNVC) across multiple nerves: median nerve (PMNCV < 0.001, PSNCV = 0.001), ulnar nerve (PMNCV = 0.02, PSNCV < 0.001), peroneal nerve (PMNCV < 0.001, PSNCV < 0.001), and tibial nerve (PMNCV = 0.001, PSNCV = 0.008). Six adverse events were reported in the HBOT group, while no adverse events occurred in the ST group, with no significant difference between the 2 groups. Publication bias was identified in some outcome variables through funnel plots, Begger test, and Egger test., Conclusions: HBOT significantly enhances treatment efficacy and nerve conduction velocity in patients with DPN, with few adverse events, making it a safe and effective adjunctive therapy for DPN., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: We aim to evaluate the efficacy of local antibiotic delivery systems in patients with diabetic foot osteomyelitis (DFO)., Methods: The Web of Science, PubMed, and Embase databases were searched for relevant publications until March 2024. All studies evaluating the efficacy of local antibiotic delivery systems in patients with DFO were included. We calculated pooled risk ratio (RR) with 95% CIs for binary outcomes and mean difference (MD) for continuous outcomes. The Cochrane's risk of bias tool and methodological index for non-randomized studies (MINORS) assessment were used to evaluate the quality of studies., Results: A total of 9 studies with 491 patients were included in this analysis. The overall healing rate in antibiotic group was 0.85 (95% CI: 0.67, 0.97). Healing rates were significantly higher in the antibiotic group compared to the control group (RR: 1.18, 95% CI: 1.01, 1.38). Furthermore, recurrence rates and amputation rates have no significantly difference between the antibiotic group and the control group (RR: 0.30, 95% CI: 0.04, 2.12 and RR: 0.22, 95% CI:0.03, 1.91), along with no significantly difference in healing time and hospital stays(MD: -7.87, 95% CI: -20.81, 5.07 and MD:-2.33, 95% CI:-5.17, 0.50). No obvious publication bias was observed in the funnel plot (Egger's test, P  = .99)., Conclusions: Our meta-analysis found that diabetic foot osteomyelitis patients treated with local antibiotic delivery systems had better healing rates than the control group. However, no significant differences were found in healing time, recurrence, hospital stays, or amputation rates. Larger randomized controlled trials are necessary in the future.

Background: Dermatomyositis (DM) is an infrequent disease subgroup of idiopathic inflammatory myopathies characterized by distinct skin lesions. However, high heterogeneity makes clinical diagnosis and treatment of DM very challenging., Objectives: Unsupervised classification in DM patients and analysis of key factors related to clinical outcomes., Methods: This retrospective study was conducted between 2017 and 2022 at the Department of Rheumatology, Xiangya Hospital, Central South University. 162 DM patients were enrolled for unsupervised hierarchical cluster analysis. In addition, we divided the clinical outcomes of DM patients into four subgroups: withdrawal, stabilization, aggravation, and death, and compared the clinical profiles amongst the subgroups., Results: Out of 162 DM patients, three clusters were defined. Cluster 1 (n = 40) was mainly grouped by patients with prominent muscular involvement and mild Interstitial Lung Disease (ILD). Cluster 2 (n = 72) grouped patients with skin rash, anti-Melanoma Differentiation Associated protein 5 positive (anti-MDA5 + ), and Rapid Progressive Interstitial Lung Disease (RP-ILD). Cluster 3 (n = 50) grouped patients with the mildest symptoms. The proportion of death increased across the three clusters (cluster 3 < cluster 1 < cluster 2)., Study Limitations: The number of cases was limited for the subsequent construction and validation of predictive models. We did not review all skin symptoms or pathological changes in detail., Conclusions: We reclassified DM into three clusters with different risks for poor outcome based on diverse clinical profiles. Clinical serological testing and cluster analysis are necessary to help clinicians evaluate patients during follow-up and conduct phenotype-based personalized care in DM., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Rheumatic diseases are a group of highly heterogeneous autoimmune and inflammatory disorders involving multiple systems. Dysfunction of immune and non-immune cells participates in the complex pathogenesis of rheumatic diseases. Therefore, studies on the abnormal activation of cell subtypes provided a specific basis for understanding the pathogenesis of rheumatic diseases, which promoted the accuracy of disease diagnosis and the effectiveness of various treatments. However, there was still a far way to achieve individualized precision medicine as the result of heterogeneity among cell subtypes. To obtain the biological information of cell subtypes, single-cell sequencing, a cutting-edge technology, is used for analyzing their genomes, transcriptomes, epigenetics, and proteomics. Novel results identified multiple cell subtypes in tissues of patients with rheumatic diseases by single-cell sequencing. Consequently, we provide an overview of recent applications of single-cell sequencing in rheumatic disease and cross-tissue to understand the cell subtypes and functions., Competing Interests: Competing interests The authors declare that there is no conflict of interest regarding the publication of this paper., (copyright: © 2022 Ding et al.)

Objective: To identify and reclassify the patients in the lupus nephritis (LN) cohort, and to further analyze the prominent clinical features and clinical significance of each cluster., Methods: In this retrospective cross-sectional study, we used a two-step clustering method to classify 635 patients with LN into different clusters, then we observed the main differences and analyzed relevant clinical significance between the clusters., Results: Cluster 1 (20.5%) presented with the highest disease severity, patients in this group had the disease for a longer duration and higher systemic lupus erythematosus disease activity index (SLEDAI) score, with multiple positive auto-antibodies and lower complement level. Patients of cluster 2 (20.8%) had lower levels of IgG, IgA and IgM, with renal function being relatively worse in this cluster than in clusters 1 and 3. Cluster 3 was the largest group (58.7%), and the patients in this group showed mild disease severity., Conclusion: This study reclassified LN patients in a large cohort into three clusters. Our classification might be helpful to implement targeted therapy at various stages of systemic lupus erythematosus., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Systemic sclerosis (SSc) is a multisystem rheumatic disease characterized by vascular dysfunction, autoimmune abnormalities, and progressive organ fibrosis. A series of studies in SSc patients and fibrotic models suggest that immune cells, fibroblasts, and endothelial cells participate in inflammation and aberrant tissue repair. Furthermore, the growing number of studies on single-cell RNA sequencing (scRNA-seq) technology in SSc elaborate on the transcriptomics and heterogeneities of these cell subsets significantly. In this review, we summarize the current knowledge regarding immune cells and stromal cells in SSc patients and discuss their potential roles in SSc pathogenesis, focusing on recent advances in the new subtypes by scRNA-seq., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Ding, Zhao, Zhu and Luo.)

Background: In the field of coordination chemistry, the introduction of heterocyclic substituents into the structure of β-diketone enables ligand to produce multiple coordination sites. The adoption of small steric oxime group into the structure of heterocyclic β-diketone by Schiff-base condensation will further increase coordination sites and facilitate the generation of polynuclear structures., Objective: A series of β-diketones (2a-2c) containing different heterocycles such as pyridine, thiophene and furan and their corresponding isoxazole compounds (3a-3c) were synthesized., Materials and Methods: The Claisen condensations were investigated in a solvent-free rheological phase system at room temperature to obtain heterocyclic β-diketones 2a-2c, which further reacted with hydroxylamine hydrochloride to obtain heterocyclic isoxazoles 3a-3c. All these compounds were well characterized by EA, IR, 1H NMR and X-ray crystal diffraction to confirm the structures. Synthetic mechanisms of compounds and the effects of different heterocycles on reactivity were discussed deeply., Results: 1H NMR indicated that these β-diketones do not exist as a total diketonic form but an equilibration between diketone and enol forms in CDCl3 solvent, in which the enol form accounts for 98.0% in 2a, 94.3% in 2b, 95.5% in 2c. While the crystal structures of 2a-2c showed that the reaction allows to isolate diketones in solid state. Crystal structures of 3a-3c showed that the neutral β-ketone oximes resonate and cyclize to form the target heterocyclic isoxazoles., Conclusion: SN1 nucleophilic substitution mechanism of Claisen ketoester condensation was proposed for the syntheses of 2a-2c, and SN1 single molecule nucleophilic substitution reaction mechanism was put forward for 3a-3c., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A sensitive, specific, accurate HPLC-MS/MS method was developed and validated for the simultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid from Longhu Rendan pills in rat plasma. Chromatographic separation was performed with a Hypersil Gold C18 column using a gradient of methanol and 0.01% acetic acid containing 0.2 mm ammonium acetate as mobile phase. The analytes were quantified on a triple quadrupole mass spectrometer, operating in selected reaction monitoring mode and switching the electrospray ion source polarity between positive and negative modes in a single run. The calibration curves of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid were linear over the concentration ranges of 5-2000, 5-2000, 0.5-200, 0.5-200, 0.25-100, 0.25-100, 0.025-10 and 0.50-200 ng mL(-1) , respectively. The intra- and inter-assay precisions and accuracies were <11.6 and 91.9-108.2%, respectively, for all analytes. Matrix effects for all analytes were between 88.2 and 114.2%. Stability testing showed that all analytes were stable in plasma at 24 °C for 3 h, at 4 °C for 24 h, after three freeze-thaw cycles, and at -80 °C for 15 days. The method was successfully applied to an in vivo study evaluating the pharmacokinetics of multiple nonvolatile compounds following intragastric administration of Longhu Rendan pills to rats. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)