arthroscopic-guided-synovectomy-synovial-biopsies-pathotype

Arthroscopic Guided Synovectomy, Synovial Biopsies, and Pathotype Identification in Refractory Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and joint destruction. Synovectomy and synovial biopsies ...

Shanghai Jiaotong University

To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA).

Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate.

MicroRNAs (miRNAs) function to fine-tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin-2 (IL-2)-related signaling pathways in systemic lupus erythematosus (SLE). The miR-31 microRNA has been found to be markedly underexpressed in patients with SLE, and thus the present study was undertaken to investigate the role of miR-31 in IL-2 defects in lupus T cells.

Identification of microRNA-31 as a novel regulator contributing to impaired interleukin-2 production in T cells from patients with systemic lupus erythematosus.

Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa.

Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo.

Polyethylenimine (PEI) is considered to be a promising non-viral gene delivery vector. To solve the toxicity versus efficacy and tumor-targeting challenges of PEI used as gene delivery vector, we constructed a novel non-viral vector DR5-TAT-modified Pluronic-PEI (Pluronic-PEI-DR5-TAT), which was based on the attachment of low-molecular-weight polyethylenimine (LMW-PEI) to the amphiphilic polymer Pluronic to prepare Pluronic-modified LMW-PEI (Pluronic-PEI). This was then conjugated to a multifunctional peptide containing a cell-penetrating peptide (TAT) and a synthetic peptide that would bind to DR5-a receptor that is overexpressed in cancer cells. The vector showed controlled degradation, favorable DNA condensation and protection performance. The Pluronic-PEI-DR5-TAT/DNA complexes at an N/P ratio of 15:1 were spherical nanoparticles of 122 ± 11.6 nm and a zeta potential of about 22 ± 2.8 mV. In vitro biological characterization results indicated that Pluronic-PEI-DR5-TAT/DNA complexes had a higher specificity for the DR5 receptor and were taken up more efficiently by tumor cells than normal cells, compared to complexes formed with PEI 25 kDa or Pluronic-PEI. Thus, the novel complexes showed much lower cytotoxicity to normal cells and higher gene transfection efficiency in tumor cells than that exhibited by PEI 25 kDa and Pluronic-PEI. In summary, our novel, degradable non-viral tumor-targeting vector is a promising candidate for use in gene therapy.

Peptide-Mediated Tumor Targeting by a Degradable Nano Gene Delivery Vector Based on Pluronic-Modified Polyethylenimine.

LS-007 is a CDK inhibitor, which exhibits potent antitumor activity against chronic lymphocytic leukemia and ovarian cancer cells. In this study, we further evaluated the antitumor activity of LS-007 alone and in combination with a Bcl-2 inhibitor ABT-199 in acute leukemia (AL) cells.

Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells.

This study aimed to explore crucial genes that contribute to the development of rheumatoid arthritis (RA). Three GSE77298, GSE55457, and GSE55235 data sets were used to analyze the differentially expressed genes (DEGs) between RA synovial membrane tissue samples and normal synovial membrane tissue samples. Then, the functional enrichment analysis and protein-protein interactions (PPIs) construction were performed for DEGs. Subsequently, submodule analysis and regulatory network that contained transcription factors (TFs), microRNAs, and their targets were conducted. Finally, small-molecule drugs related to the DEGs were predicted. A total of 173 upregulated and 54 downregulated DEGs identified in at least 2 of 3 data sets. , , , , and  were both highlighted in the PPI and submodule networks. In addition, miR-101,  TF, , and  had high degree in the regulatory network, and regulation pairs of miR-101- and  TF- were obtained. Drugs such as alemtuzumab and marimastat were negatively related to expression of the DEGs and might be useful drugs for RA treatment. In addition, most DEGs were involved in innate immune response (e.g., , , , , and ) and phagosome pathway (e.g., ). We suggested that miR-101 that regulated ,  TF that regulated , as well as  as  and  might contribute to the RA pathogenesis. In addition, anti-inflammatory agent alemtuzumab and matrix metalloproteinase inhibitor marimastat might be useful drugs for RA treatment through functioning on their target genes.

Overexpression of miR-101 May Target DUSP1 to Promote the Cartilage Degradation in Rheumatoid Arthritis.

Gangrene of nose in granulomatosis with polyangiitis.

The effect of vaginal microbiota on spontaneous preterm birth (sPTB) has not been fully addressed, and few studies have explored the associations between vaginal taxa and sPTB in the gestational diabetes mellitus (GDM) and non-GDM groups, respectively. . To minimize external interference, a total of 41 pregnant women with sPTB and 308 controls (pregnant women without sPTB) from same regain were enrolled in this case-cohort study. Controls were randomly selected at baseline. With the exception of GDM, other characteristics were not significantly different between the two groups. Vaginal swabs were collected at early second trimester. Using 16S amplicon sequencing, the main bioinformatics analysis was performed on the platform of QIIME 2. Vaginal microbiota traits of the sPTB group were compared with controls. Finally, the effects of binary taxa on sPTB in the GDM group and the non-GDM group were analyzed, respectively.

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women.

Preterm prelabor rupture of membranes (PPROM) is a major cause of spontaneous preterm birth (sPTB), one of the greatest challenges facing obstetrics with complicated pathogenesis. This case-cohort study investigated the association between vaginal bacteriome of singleton pregnant females in the early second trimester and PPROM. The study included 35,255 and 180 pregnant females with PPROM as cases and term-birth without prelabor rupture of membranes (TWPROM) and term prelabor rupture of membranes (TPROM) pregnant females as controls, respectively. Using 16S rRNA sequencing, the vaginal microbiome traits were analyzed. Females with PPROM had higher alpha and beta diversity (P < 0.05) than TWPROM and TPROM. The presence of L. mulieris was associated with a decreased risk of PPROM (adjusted odds ratio [aOR] = 0.35; 95% confidence interval [CI]: 0.17-0.72) compared with TWPROM. Meanwhile, the presence of Megasphaera genus (aOR = 2.27; 95% CI: 1.09-4.70), Faecalibacterium genus (aOR = 3.29; 95% CI: 1.52-7.13), Bifidobacterium genus (aOR = 3.26; 95% CI: 1.47-7.24), Xanthomonadales genus (aOR = 2.76; 95% CI: 1.27-6.01), Gammaproteobacteria class (aOR = 2.36; 95% CI: 1.09-5.14), and Alphaproteobacteria class (aOR = 2.45; 95% CI: 1.14-5.26) was associated with an increased risk of PPROM compared with TWPROM. Our results indicated that the risk of PPROM can decrease with vaginal L. mulieris but increase with high alpha or beta diversity, and several vaginal bacteria in pregnant females may be involved in the occurrence of PPROM.

Preterm Prelabor Rupture of Membranes Linked to Vaginal Bacteriome of Pregnant Females in the Early Second Trimester: a Case-Cohort Design.

The treatment of primary Sjögren's syndrome (pSS) coexisting with neuromyelitis optica spectrum disorder (NMOSD) using protein-A immunoadsorption combined with immunosuppressive therapy has rarely been reported. Herein, we present the case of a 35-year-old female diagnosed with pSS concomitant with NMOSD (pSS-NMOSD) who demonstrated a positive response to protein-A immunoadsorption after failing to respond to therapy comprising high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). Within one week of receiving three sessions of immunoadsorption combined with immunosuppressive treatment, the patient's clinical symptoms (blurred vision, paraparesis, and dysfunctional proprioception) significantly improved. Additionally, a rapid decrease in the circulating levels of Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), immunoglobulin (Ig) A, IgG, IgM, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were observed. Magnetic resonance imaging (MRI) further revealed a significant reduction in the lesions associated with longitudinal extensive transverse myelitis. During the follow-up period, prednisolone was gradually tapered to a maintenance dose of 5-10 mg/day, whereas mycophenolate mofetil (MMF) was maintained at 1.0-1.5 g/day. The patient's condition has remained stable for four years, with no signs of recurrence or progression observed on imaging examination. Therefore, this case suggests that protein A immunoadsorption may represent a potentially effective therapeutic option for patients with pSS-NMOSD who are refractory to conventional treatments.

Protein-A immunoadsorption combined with immunosuppressive treatment in refractory primary Sjögren's syndrome coexisting with NMOSD: a case report and literature review.

The increasing diversity of emerging pollutants poses significant risks to aquatic ecosystems, particularly in terms of genotoxicity. Monitoring genetic damage in model organisms can offer early warnings about environmental risks linked to emerging pollutants. The common use of the comet assay in genotoxicity necessitates the creation of high-throughput methods for broader application. The aim of this study was to develop a deep learning (DL)-based high-throughput comet assay analysis method for automated, accurate detection and evaluation of DNA damage. This research introduces a technique utilizing DL algorithms for automated analysis of image batches, from raw inputs to results. The DL method employs the You Only Look Once version 8 model for comet detection on a dataset with 1453 training images and 364 validation images, with 6749 manually annotated comet subjectives. The DL method achieves 90.6 % accuracy for comets with tails. Comparative analysis with traditional methods was conducted, showing the DL method's effectiveness in genotoxicity evaluation. Application of the DL method and Comet Assay Software Project (CASP) for assessing genotoxicity induced by combined stressors (polyethylene microplastics and sulfamethoxazole) in mussel gills revealed that while individual exposure to either stressor significantly increased DNA damage, their co-exposure exhibited a mitigating effect on overall genotoxicity. The DL method correlated strongly with the CASP method (R= 1.09, P < 0.01). This integrated approach combines classical toxicology with DL to provide an efficient and accurate way to assess DNA damage from emerging pollutants.

Article	Year
Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate. Arthritis and rheumatism\| PubMed ID: 19565542	2009
Identification of microRNA-31 as a novel regulator contributing to impaired interleukin-2 production in T cells from patients with systemic lupus erythematosus. Arthritis and rheumatism\| PubMed ID: 22736314	2012
Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo. International journal of nanomedicine\| PubMed ID: 25473281	2014
Peptide-Mediated Tumor Targeting by a Degradable Nano Gene Delivery Vector Based on Pluronic-Modified Polyethylenimine. Nanoscale research letters\| PubMed ID: 26932761	2016
Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells. Acta pharmacologica Sinica\| PubMed ID: 27569395	2016
Overexpression of miR-101 May Target DUSP1 to Promote the Cartilage Degradation in Rheumatoid Arthritis. Journal of computational biology : a journal of computational molecular cell biology\| PubMed ID: 31246497	2019
Gangrene of nose in granulomatosis with polyangiitis. Rheumatology advances in practice\| PubMed ID: 35155986	2022
Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women. BioMed research international\| PubMed ID: 36506912	2022
Preterm Prelabor Rupture of Membranes Linked to Vaginal Bacteriome of Pregnant Females in the Early Second Trimester: a Case-Cohort Design. Reproductive sciences (Thousand Oaks, Calif.)\| PubMed ID: 36725814	2023
Protein-A immunoadsorption combined with immunosuppressive treatment in refractory primary Sjögren's syndrome coexisting with NMOSD: a case report and literature review. Frontiers in immunology\| PubMed ID: 39055718	2024
Evaluating microplastics and antibiotics induced genotoxicity in marine mussels through deep learning-based processing images of comet assay. Ecotoxicology and environmental safety\| PubMed ID: 41138450	2025

Wei Fan

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