Microbiome dysbiosis in patients with chronic endometritis and Clostridium tyrobutyricum ameliorates chronic endometritis in mice.

Chronic endometritis is associated with the imbalance of female reproductive tract microbiota and pathogenic microbial infection. This study aimed to identify the specific changes in the endometrial microbiome in patients with endometritis and to explore how Clostridium tyrobutyricum (C.t) influences the progression of endometritis in mice for further elucidating endometritis pathogenesis. For this purpose, endometrial tissues from 100 participants were collected and divided into positive, weakly positive, and negative groups based on CD138 levels, while endometrial microbiome differences were detected and analyzed using 16S rRNA gene sequencing. Staphylococcus aureus (S. aureus)-induced endometritis mouse model was established, followed by treatment with C.t, and inflammatory response, epithelial barrier, and TLR4/NF-κB pathway were evaluated. Results showed that α- and ß-diversity was significantly lower in the positive group compared with the weakly positive or negative groups, where the negative group had more unique operational taxonomic units. The abundance of Proteobacteria was found to be increased, while that of Actinobacteria, Firmicutes, and Bacteroidetes was found to be reduced in the positive group, while the area under the curve value was found to be 0.664. Furthermore, C.t treatment resulted in the alleviation of S. aureus-induced inflammatory response, epithelial barrier damage, and activation of the TLR4/NF-κB pathway in mice. Clinical samples analysis revealed that the diversity and abundance of microbiota were altered in patients with endometritis having positive CD138 levels, while mechanistic investigations revealed C.t alleviated S. aureus-induced endometritis by inactivating TLR4/NF-κB pathway. The findings of this study are envisaged to provide a diagnostic and therapeutic potential of microbiota in endometritis.

Human umbilical cord mesenchymal stem cell-derived exosomes loaded miR-451a targets ATF2 to improve rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation, with synovial fibroblasts (SFs) playing a pivotal role in its pathogenesis. Dysregulation of microRNA (miRNA) expression in SFs contributes to RA development. Exosomes (Exos) have emerged as effective carriers for therapeutic molecules, facilitating miRNA transfer between cells. This study explores the therapeutic potential of Exos derived from human umbilical cord mesenchymal stem cells (hUCMSCs), loaded with miR-451a, to modulate ATF2 expression, aiming to address RA in both in vivo and in vitro settings. METHODS: In this study, hUCMSC and RA SFs were isolated and identified, and hUCMSC-Exos were extracted and characterized. The influence of hUCMSC-Exos on RA SFs was detected. And hUCMSC-Exos targeting RA SFs was traced. HUCMSCKD-AGO2 was prepared by knocking down AGO2 in hUCMSC. HUCMSCKD-AGO2-Exos was extracted and characterized,and their influence on RA SFs was detected. The miRNA profiles before and after hUCMSC-Exos intervention in RA SFs were mapped to identify differential miRNAs. RT-qPCR was used to verify the differential miRNAs, with hsa-miR-451a finally selected as the target gene. The effect of miR-451a on SFs was detected. The latent binding of miR-451a to activating transcription factor 2 (ATF2) was analyzed. The effect of hUCMSC-ExosmiR-451a on SFs was detected, and the expression of miR-451a and ATF2 was measured by RT-PCR. In vivo, hUCMSC-ExosmiR-451a was injected into the ankle joint of CIA rats, and arthritis index, joint imaging and synovial pathology were assessed. The expression of miR-451a and ATF2 in synovial tissue was detected. Finally, the safety of hUCMSC-ExosmiR-451a in CIA rats was evaluated. RESULTS: This study revealed that hUCMSC-Exos can inhibit RA SFs proliferation, migration and invasion through miRNAs. High throughput sequencing detected 13 miRNAs that could be transmitted from hUCMSCs to RA SFs via hUCMSC-Exos. miR-451a inhibited RA SFs proliferation, migration and invasion by regulating ATF2. hUCMSC-Exos loaded with miR-451a targeted ATF2 to inhibit RA SFs proliferation, migration and invasion, and improve joint inflammation and imaging findings in CIA rats. CONCLUSIONS: This study demonstrates that miR-451a carried by hUCMSC-Exos can play a role in inhibiting RA SFs biological traits and improving arthritis in CIA rats by inhibiting ATF2. The findings suggest a promising treatment for RA and provide insights into the mechanism of action of hUCMSC-Exos in RA. Future research directions will continue to explore the potential in this field.

A manual controlled theranostic nanoplatform with real-time photoacoustic quantification of drug release for chemophotothermal therapy.

The development of intelligent nanodrug delivery systems that can visually guide the on-demand quantitative control of drug release has received extensive attention. Herein, two chemotherapeutic drugs, gallic acid and 5-fluorouracil, and Fe(III) were selected to prepare nanomedicine GF-Fe via polyphenol-metal self-assembly and infinite coordination of drug-metal. GF-Fe has good biocompatibility, photothermal properties and photoacoustic (PA) signals. When deferoxamine (DFO) was artificially applied and interacted with GF-Fe, GF-Fe began to disassemble, gallic acid and 5-fluorouracil were gradually released, while the PA signal of the nanomedicine decayed synchronously. Based on this, the relationship between the intensity of the PA signal and the drug release amount was established, so as to realize the precise quantitative control of the drug release in real-time under the guidance of PA imaging. Besides, the combined effect of the two therapeutic drugs in combination with photothermal therapy (PTT) can improve the therapeutic effect, resulting in significant superadditiveness. This nanoplatform constructed by facile synthesis provided good clinical translation potential for the implementation of precise multimodal combination therapy strategies for tumors.

Long-term secular trends in dermatomyositis and polymyositis mortality in the USA from 1981 to 2020 according to underlying and multiple cause of death mortality data.

BACKGROUND: People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data. METHODS: We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis. RESULTS: We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD. CONCLUSION: We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.

Construction of Artificial Controllable Aggregation Trojan Horse-Like Nanoplatform for Enhanced NIR-II Photothermal Therapy.

Promoting the aggregation of nanoprobes at tumor sites and realizing precise imaging and treatment of tumors is still one of the important problems to be solved in the field of nanomedicine. Poly-2-phenylbenzobisthiazole (PB) is a novel conjugated polymer with good biocompatibility, excellent photothermal properties in the second near-infrared region (NIR-II), but poor water dispersibility. Herein, a novel self-assembly/polymerization two-in-one strategy was proposed to prepare a new family of poly-2-phenyl-benzobisthiazole-based nanoparticles. Because the hydrophobic polymer PB was well "camouflaged" in the hydrophilic polyphenol-metal networks, the prepared "Trojan horse-like" nanoparticle TF-PB exhibited good water dispersibility. Besides, TF-PB can play a role as a contrast agent for photoacoustic and magnetic resonance dual-modality imaging. When deferoxamine was artificially applied and interacted with TF-PB, the polyphenol-metal networks disintegrated and the hydrophobic material PB was exposed and started hydrophobic aggregation. Thus, it can be applied for precise enhanced photothermal therapy (PTT) in the NIR-II. Meanwhile, the aggregation process enabled non-invasive, fast, and accurate real-time monitoring by self-enhancing photoacoustic imaging. This work has realized the artificially controllable aggregation of photothermal materials in the tumor site, solved the limitations of traditional PTT, and also has good application prospects in clinical therapy.

Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA), which affects nearly 1% of the world's population, is a debilitating autoimmune disease. Bone erosion caused by periarticular osteopenia and synovial pannus formation is the most destructive pathological changes of RA, also leads to joint deformity and loss of function,and ultimately affects the quality of life of patients. Osteoclasts (OCs) are the only known bone resorption cells and their abnormal differentiation and production play an important role in the occurrence and development of RA bone destruction; this remains the main culprit behind RA. Method: Based on the latest published literature and research progress at home and abroad, this paper reviews the abnormal regulation mechanism of OC generation and differentiation in RA and the possible targeted therapy. Result: OC-mediated bone destruction is achieved through the regulation of a variety of cytokines and cell-to-cell interactions, including gene transcription, epigenetics and environmental factors. At present, most methods for the treatment of RA are based on the regulation of inflammation, the inhibition of bone injury and joint deformities remains unexplored. Discussion: This article will review the mechanism of abnormal differentiation of OC in RA, and summarise the current treatment oftargeting cytokines in the process of OC generation and differentiation to reduce bone destruction in patients with RA, which isexpected to become a valuable treatment choice to inhibit bone destruction in RA.

Research progress of risk factors and early diagnostic biomarkers of gout-induced renal injury.

Gout renal injury has an insidious onset, no obvious symptoms, and laboratory abnormalities in the early stages of the disease. The injury is not easily detected, and in many cases, the patients have entered the renal failure stage at the time of diagnosis. Therefore, the detection of gout renal injury-related risk factors and early diagnostic biomarkers of gout renal injury is essential for the prevention and early diagnosis of the disease. This article reviews the research progress in risk factors and early diagnostic biomarkers of gout renal injury.

Bibliometric and visualization analysis of mesenchymal stem cells and rheumatoid arthritis (from 2012 to 2021).

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint deformity and loss of function. Recent studies have shown great progress in the research of mesenchymal stem cells (MSCs) in RA. However, thus far, there have been no bibliometric or visualization analyses in this field. This bibliometric analysis provides a comprehensive overview of the general information and research hotspots of MSCs and RA. Methods: Articles relevant to MSCs and RA, published between 2012 and 2021, were searched using the Web of Science Core Collection database. Irrelevant publications were excluded from the analysis. Bibliometric and visualization analyses were conducted using VOSviewer, CiteSpace, and Scimago Graphica. Results: A total of 577 articles were analyzed. The annual number of publications increased from 2012 to 2017 and plateaued from 2017 to 2021. China and the USA had the largest number of publications. Collaboration among different organizations mainly occurs between institutes of the same country. Stem Cell Research and Therapy and Frontiers in Immunology were the most popular journals in this field. All the top 20 co-cited authors had a positive co-citation relationship. The top references indicate that MSCs can contribute to RA research and treatment mainly via immunomodulation. From 2012 to 2021, "collagen-induced arthritis," "immunomodulation," and "therapy" were some of the keywords associated with MSCs and RA, while "extracellular vesicles" showed a strong keyword burst from 2019 to 2021. Conclusion: MSCs and RA have been widely studied in different countries and institutions and by different authors over the last ten years. China and the USA had the largest number of publications. Different types of journals provide admirable sources for researchers. Some keywords, including immunomodulation and extracellular vesicles, may be hot spots in the near future. There will be more basic research and clinical translation of MSCs and RA, and substantial new treatments for RA will soon be developed.

Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002-2021).

Background: Autoimmune diseases (AIDs) are a class of chronic disabling diseases characterized by inflammation and damage to muscles, joints, bones, and internal organs. Recent studies have shown that much progress has been made in the research of exosomes in AIDs. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of exosomes in AIDs through bibliometrics. Method: Publications related to exosomes in AIDs from 2002 to 2021 were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package "bibliometrix" were used to conduct this bibliometric analysis. Results: 312 articles from 48 countries led by China and the United States were included. The number of publications related to exosomes in AIDs is increasing year by year. Central South University, Sun Yat Sen University, Tianjin Medical University and University of Pennsylvania are the main research institutions. Frontiers in immunology is the most popular journal in this field, and Journal of Immunology is the most co-cited journal. These publications come from 473 authors among which Ilias Alevizos, Qianjin Lu, Wei Wei, Jim Xiang and Ming Zhao had published the most papers and Clotilde Théry was co-cited most often. Studying the mechanism of endogenous exosomes in the occurrence and development of AIDs and the therapeutic strategy of exogenous exosomes in AIDs are the main topics in this research field. "Mesenchymal stem cells", "microRNA", "biomarkers", "immunomodulation", and "therapy" are the primary keywords of emerging research hotspots. Conclusion: This is the first bibliometric study that comprehensively summarizes the research trends and developments of exosomes in AIDs. This information identifies recent research frontiers and hot directions, which will provide a reference for scholars studying exosomes.

Mesenchymal stem cells and their microenvironment.

Mesenchymal stem cells (MSCs), coming from a wide range of sources, have multi-directional differentiation ability. MSCs play vital roles in immunomodulation, hematopoiesis and tissue repair. The microenvironment of cells often refers to the intercellular matrix, other cells, cytokines and humoral components. It is also the place for cells' interaction. The stability of the microenvironment is pivotal for maintaining cell proliferation, differentiation, metabolism and functional activities. Abnormal changes in microenvironment components can interfere cell functions. In some diseases, MSCs can interact with the microenvironment and accelerate disease progression. This review will discuss the characteristics of MSCs and their microenvironment, as well as the interaction between MSCs and microenvironment in disease.

Effect of long-duration oxygen vs room air during labor on umbilical cord venous partial pressure of oxygen: a randomized controlled trial.

BACKGROUND: There are limited data to guide the duration and dose of oxygen supplementation for pregnant women undergoing labor. OBJECTIVE: To assess the effect of maternal long-duration high-concentration oxygen administration during labor on umbilical cord venous partial pressure of oxygen. STUDY DESIGN: This randomized clinical trial was conducted between January and October of 2021 in the obstetrics wards of 3 tertiary teaching hospitals in Beijing, China. Women undergoing the latent phase of labor with no existing medical conditions or obstetrical complications who were admitted for delivery were eligible. The women who met inclusion criteria with category I fetal heart rate tracings in labor were randomized in a 1:1 ratio to oxygen or room air. The oxygen group received 10 L of oxygen per minute by simple, tight-fitting face mask until delivery. The room-air group received room air only, without a face mask. The primary outcome was the umbilical cord venous partial pressure of oxygen. RESULTS: A total of 661 women were screened, and 521 were excluded; 140 participants with category I fetal heart rate tracings were enrolled and randomized to oxygen (N=70) or room air (N=70). A total of 135 women with valid paired umbilical cord venous and arterial gas values were included in the umbilical cord venous partial pressure of oxygen and arterial pH analyses. All 140 women were included in the fetal heart rate tracings analysis. Baseline characteristics were similar between the oxygen and room-air groups. The duration of oxygen exposure was approximately 322±147 minutes. There were no differences between the oxygen and room-air groups in the umbilical cord venous partial pressure of oxygen (mean difference, 1.1 mm Hg; 95% confidence interval, -1.0 to 3.2; P=.318) or the proportion of participants with category II fetal heart rate tracings (81.4% vs 78.6%; relative risk, 1.04; 95% confidence interval, 0.88-1.22; P=.672). However, the umbilical cord arterial pH was significantly lower in the oxygen group than in the room-air group (median, 7.23; interquartile range, 7.20-7.27 vs median 7.27; interquartile range, 7.20-7.30; P=.005). CONCLUSION: Maternal long-duration high-concentration oxygen administration during labor did not affect either the umbilical cord venous partial pressure of oxygen or fetal heart rate pattern distribution but resulted in a deterioration of the umbilical cord arterial pH at birth.

Secular trends in cryoglobulinemia mortality in the USA in the era of direct-acting antivirals.

BACKGROUND: Hepatitis C virus (HCV) is the main etiology of cryoglobulinemia with mortality around 25%. Little is known on the changes in cryoglobulinemia mortality after the introduction of direct-acting antivirals (DAA) for treatment of HCV in 2014 in the USA. METHODS: We used the multiple-cause mortality files compiled by the National Center for Health Statistics to calculate cryoglobulinemia mortality from 1999 to 2018. The proportionate mortality ratio (PMR) of cryoglobulinemia cases with HCV and those with autoimmune diseases was computed to assess the impact of introduction of DAA. RESULTS: We identified 1299 people aged ≥ 20 years who died with cryoglobulinemia between 1999 and 2018. The cryoglobulinemia mortality (deaths per million) declined from 1999 (0.4) to 2010 (0.22) and mildly increased to 2014 (0.26), and then decreased abruptly from 2014 to 2018 (0.19) with annual percent change of - 14.3%. The proportion of cryoglobulinemia patients with HCV was 39% (118/302) in 2009-2013 and 26% (81/310) in 2014-2018, with a PMR of 0.67 (95% CI 0.50-0.89). By contrast, the proportion of cryoglobulinemia patients with systemic autoimmune diseases was 2.6% (8/302) in 2009-2013 and 4.2% (13/310) in 2014-2018, with a PMR of 1.58 (95% CI 0.66-3.82). CONCLUSION: The changes in cryoglobulinemia mortality during the past two decades are mainly related to the aging and dying of the "baby boomer" cohort who had a high HCV prevalence and to the introduction of a DAA in 2014.

The Mechanism of Stem Cell Aging.

Stem cells have self-renewal ability and multi-directional differentiation potential. They have tissue repair capabilities and are essential for maintaining the tissue homeostasis. The depletion of stem cells is closely related to the occurrence of body aging and aging-related diseases. Therefore, revealing the molecular mechanisms of stem cell aging will set new directions for the therapeutic application of stem cells, the study of aging mechanisms, and the prevention and treatment of aging-related diseases. This review comprehensively describes the molecular mechanisms related to stem cell aging and provides the basis for further investigations aimed at developing new anti-stem cell aging strategies and promoting the clinical application of stem cells.

B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects.

Rheumatoid arthritis (RA) is a common, chronic, systemic autoimmune disease, and its clinical features are the proliferation of joint synovial tissue, the formation of pannus and the destruction of cartilage. The global incidence of RA is about 1%, and it is more common in women. The basic feature of RA is the body's immune system disorders, in which autoreactive CD4+T cells, pathogenic B cells, M1 macrophages, inflammatory cytokines, chemokines and autoantibodies abnormally increase in the body of RA patients B cell depletion therapy has well proved the important role of B cells in the pathogenesis of RA, and the treatment of RA with B cells as a target has also been paid more and more attention. Although the inflammatory indicators in RA patients receiving B-cell depletion therapy have been significantly improved, the risk of infection and cancer has also increased, which suggests that we need to deplete pathogenic B cells instead of all B cells. However, at present we cannot distinguish between pathogenic B cells and protective B cells in RA patients. In this review, we explore fresh perspectives upon the roles of B cells in the occurrence, development and treatment of RA.

Fibroblast Activation Protein-α as a Target in the Bench-to-Bedside Diagnosis and Treatment of Tumors: A Narrative Review.

Fibroblast activation protein-α (FAP) is a type II integral serine protease that is specifically expressed by activated fibroblasts. Cancer-associated fibroblasts (CAFs) in the tumor stroma have an abundant and stable expression of FAP, which plays an important role in promoting tumor growth, invasion, metastasis, and immunosuppression. For example, in females with a high incidence of breast cancer, CAFs account for 50-70% of the cells in the tumor's microenvironment. CAF overexpression of FAP promotes tumor development and metastasis by influencing extracellular matrix remodeling, intracellular signaling, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. This review discusses the basic biological characteristics of FAP and its applications in the diagnosis and treatment of various cancers. We review the emerging basic and clinical research data regarding the use of nanomaterials that target FAP.

Simultaneous determination of triazine herbicides and their metabolites in shellfish by HPLC-MS/MS combined with Q/E-Orbitrap HRMS.

Triazine herbicides are used extensively in agriculture and aquaculture worldwide because of their broad effectiveness in weed control. However, after they are discharged into the sea, they seriously contaminate aquatic ecosystems and threaten aquatic organisms, especially shellfish. Currently, there are no established methods for the detection and confirmation of triazine herbicides and their metabolites in biological matrixes. Hence, the food safety of aquatic products cannot be accurately evaluated, which creates a technical barrier against international aquatic product trade. In this study, for the first time, a method was developed for the analysis and confirmation of seven triazine herbicides and 13 metabolites in shellfish, based on alkaline acetonitrile extraction and neutral Al2O3 cartridge purification coupled with internal standard calibration. Specifically, quantitative and qualitative analysis was conducted using high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS), and accurate identification was carried out by quadrupole orbitrap high-resolution mass spectrometry (Q/E Orbitrap HRMS). The results showed that target analytes demonstrated good linearity within the corresponding range (R2 > 0.995). The limit of detection and limit of quantitation of the proposed method were 0.1 and 0.3 µg/kg, respectively. The average recoveries of analytes were between 70.0% and 120% when spiked at three levels with blank oyster (Crassostrea gigas) as the matrix, and the relative standard deviations (RSDs) were all less than 12% (n=6). The proposed method was successfully applied for the detection of triazine herbicide residues in oyster samples during actual breeding, and the presence of DIP, HP, DEHA, and other metabolites in positive samples was confirmed by Q/E Orbitrap HRMS. This method exhibits high accuracy, high sensitivity, and good reproducibility. It has promising application prospects in the field of hazard analysis and the positive identification of aquatic products.

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate collagen-induced arthritis via immunomodulatory T lymphocytes.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease for which there are currently no effective therapies. Although mesenchymal stem cells (MSCs) can prevent arthritis through immunomodulatory mechanisms, there are several associated risks. Alternatively, MSC-derived small extracellular vesicles (sEVs) can mimic the effects of MSCs, while reducing the risk of adverse events. However, few studies have examined sEVs in the context of RA. Here, we evaluate the immunomodulatory effects of human umbilical cord MSC (hUCMSC)-derived sEVs on T lymphocytes in a collagen-induced arthritis (CIA) rat model to elucidate the possible mechanism of sEVs in RA treatment. We then compare these mechanisms to those of MSCs and methotrexate (MTX). METHODS: The arthritis index and synovial pathology were assessed. T lymphocyte proliferation and apoptosis, Th17 and Treg proportions, and interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-ß expression were detected using flow cytometry. Retinoic acid receptor-related orphan receptor gamma t (RORγt) and forkhead box P3 (FOXP3), which are master transcriptional regulators of Th17 and Treg differentiation, were also assessed using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: sEV treatment ameliorated arthritis and inhibited synovial hyperplasia in a dose-dependent manner. These effects were mediated by inhibiting T lymphocyte proliferation and promoting their apoptosis, while decreasing Th17 cell proportion and increasing that of Treg cells in the spleen, resulting in decreased serum IL-17, and enhanced IL-10 and TGF-ß expression. Transcriptionally, sEVs decreased RORγt and increased FOXP3 expression in the spleen, and decreased RORγt and FOXP3 expression in the joints. In some aspects sEVs were more effective than MSCs and MTX in treating CIA. CONCLUSIONS: hUCMSC-derived sEVs ameliorate CIA via immunomodulatory T lymphocytes, and might serve as a new therapy for RA.

Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis.

OBJECTIVES: This meta-analysis aimed to evaluate the effectiveness of HCQ in improving the maternal and fetal outcomes in pregnancies with SLE. METHODS: A literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane database for relevant English language articles, and Wanfang, CNKI and VIP for Chinese articles, from the databases' inception to April 30, 2020. These studies compared the maternal and/or fetal outcomes between pregnant patients with SLE who were administered HCQ during pregnancy (HCQ+ group) and those who were not administered HCQ (HCQ- group). Two investigators extracted the data and assessed the quality using the Newcastle-Ottawa Scale (NOS) and GRADE criteria independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted using the Stata 12.0 software. RESULTS: Nine studies involving 1132 pregnancies were included in the study (3 case controls, 2 prospective cohorts, 4 retrospective cohorts). Preeclampsia, gestational hypertension, and prematurity were significantly lower in the HCQ+ group than in the HCQ- group (OR 0.35, 95% CI 0.21-0.59), (OR 0.41, 95% CI 0.19-0.89) and (OR 0.55, 95% CI 0.36-0.86), respectively. There were no significant differences in the rates of HELLP Syndrome (OR 0.88, 95% CI 0.19-3.96), gestational diabetes (OR 2.3, 95% CI 0.44-12.12), thrombotic events (OR 0.26, 95% CI 0.05-1.51), spontaneous abortion (OR 1.77, 95% CI 0.96-3.26), premature rupture of membranes (OR 0.58, 95% CI 0.24-1.39), oligohydramnios (OR 0.90, 95% CI 0.38-2.14), live birth (OR 1.22, 95% CI 0.60-2.47), stillbirth (OR 1.00, 95% CI 0.50-2.00), congenital malformation (OR 0.53, 95% CI 0.14-2.04), low birth weight (OR 0.77, 95% CI 0.43-1.39), intrauterine distress (OR 1.07, 95% CI 0.41-2.76,), intrauterine growth restriction (OR 0.57, 95% CI 0.06-5.43), or five-minute APGAR score <7 (OR 0.72, 95% CI 0.20-2.58) between the two groups. CONCLUSIONS: HCQ treatment during pregnancy could reduce the risk of preeclampsia, pregnancy hypertension and prematurity in SLE patients. The certainty of evidence is high but majority of the studies included are retrospective studies and not randomized controlled trials. Therefore, the multidisciplinary management of pregnant patients with SLE should promote HCQ use, irrespective of disease activity or severity.

Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects synovial joints. During the course of RA, the synovium transforms into hyperplastic invasive tissue, leading to cartilage and bone destruction. Fibroblast-like synoviocytes (FLS) in the synovial lining develop aggressive phenotypes and produce pathogenic mediators that lead to the occurrence and progression of disease, playing a major role in RA pathophysiology. Therefore, research on FLS has become the main focus within the RA field. With technical advances and the development of multi-omics comprehensive analysis approaches, it has become possible to identify different FLS subsets via high-throughput sequencing and investigate differences between FLS phenotypes, allowing for the detailed study of RA pathogenesis. This review summarizes recent works on FLS subtypes and the surface marker proteins identified for different subtypes, providing a theoretical basis and reference for future studies on FLS in RA. The current work also addresses the clinical potential of FLS surface markers in RA based on related research from other fields.

Pentraxin 3 is more accurate than C-reactive protein for Takayasu arteritis activity assessment: A systematic review and meta-analysis.

AIMS: Whether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein (CRP) in TAK activity assessment has been investigated in this study. STUDY DESIGN: Research works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model. RESULTS: Totally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, p<0.0001; I2 = 68%, p of Q test = 0.003). And there was no publication bias. Among the 8 studies, 5 studies identified active TAK with both PTX3 and CRP. The pooled sensitivity, specificity, and AUC values of PTX3 in active TAK diagnosis were higher than those of CRP (0.78 [95% CI = 0.65-0.87] vs. 0.66 [95% CI = 0.53-0.77], p = 0.012; 0.85 [95% CI = 0.77-0.90] vs. 0.77 [95% CI = 0.56-0.90], p = 0.033; 0.88 [95% CI = 0.85-0.90] vs. 0.75 [95% CI = 0.71-0.79], p < 0.0001). It showed potential publication bias using Egger's test (p of PTX3 = 0.031 and p of CRP = 0.047). CONCLUSIONS: PTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.