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ID PMID Title PublicationDate abstract
31464668 Thymic stromal lymphopoietin expression from benign lymphoproliferation to malignant B-cel 2019 May OBJECTIVES: To investigate the expression of thymic stromal lymphopoietin (TSLP) in primary Sjögren's syndrome (pSS), stratified according to the lymphoproliferative status, from a fully benign (fbSS) stage to myoepithelial sialadenitis (MESA) and to B-cell non-Hodgkin's lymphoma (NHL). METHODS: After initial serum studies in large numbers of pSS patients and in controls, TSLP was investigated also in pathologic salivary glands (SG) biopsies from 38 stratified pSS patients (13 fbSS; 13 MESA; 12 NHL) and from 13 controls with non-autoimmune sicca syndrome (nSS) by RT-PCR, immunohistochemistry and immunofluorescence. RESULTS: Significantly higher TSLP serum levels were shown in pSS than controls, increasing from fbSS to MESA and to NHL. In SG biopsies, TSLP-positive B lymphocytes increased with increasing lymphoproliferation, maximally in NHL, consistent with the detection of inducible TSLP long isoform (lfTSLP) mRNA only in MESA and NHL. By contrast, the constitutive TSLP short isoform (sfTSLP) mRNA showed no difference among subgroups. The TSLP expression by glandular epithelium declined with the progression from fbSS to MESA and to NHL. CONCLUSIONS: TSLP progressively increases from benign to malignant B-cell lymphoproliferation in pSS. The salivary epithelium expresses TSLP but, with the progression of lymphoproliferation, the B-cells may represent the major source of TSLP, in its long inducible isoform. A possible pathogenetic role of TSLP is herein hypothesised in pSS for the first time. Further analyses on TSLP, also as a biomarker of pSS and related lymphoproliferation, are worthwhile.
30280368 The efficacy and safety of total glucosides of peony in the treatment of primary Sjögren' 2019 Mar To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults with primary Sjögren's syndrome (pSS). A multi-center, randomized, double-blinded, placebo-controlled study was conducted between March 2012 and July 2014 at ten Chinese hospitals. In total, 320 pSS patients-classified according to the 2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo group. Study personnel, investigators, and patients were blinded to the treatment grouping. The primary endpoint was the improvement of EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate (ESR). All adverse events were recorded during the trial period. ESSPRI improved more in the TGP than the placebo group (p < 0.001). Dry eyes/throat/vagina VAS, fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved more in the TGP group than in the placebo group (all p < 0.05). Stimulated salivary flow-rate values increased in the TGP group at week 12 but not at week 24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well tolerated by study subjects. TGP seems to be an effective and safe treatment for pSS.
30044541 The Incidence and Prevalence of Adult Primary Sjögren's Syndrome in New York County. 2019 Jul OBJECTIVE: Extant epidemiologic data of primary Sjögren's syndrome (SS) remains limited, particularly for racial/ethnic populations in the US. The Manhattan Lupus Surveillance Program (MLSP) is a population-based retrospective registry of cases of systemic lupus erythematosus and related diseases, including primary SS in Manhattan, New York. The MLSP was used to provide estimates of the incidence and prevalence of primary SS across major racial/ethnic populations. METHODS: MLSP cases were identified from hospitals, rheumatologists, and population databases. Three case definitions were used for primary SS, including physician diagnosis, rheumatologist diagnosis, and modified primary SS criteria. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess underascertainment of cases. RESULTS: By physician diagnosis, age-adjusted overall incidence and prevalence rates of primary SS among adult Manhattan residents were 3.5 and 13.1 per 100,000 person-years, respectively. Capture-recapture adjustment increased incidence and prevalence rates (4.1 and 14.2 per 100,000 person-years, respectively). Based on physician diagnosis, incidence and prevalence rates were approximately 6 times higher among women than men (P < 0.001). Incidence of primary SS was statistically higher among non-Latina Asian women (10.5) and non-Latina white women (6.2) compared with Latina women (3.2). Incidence was also higher among non-Latina Asian women compared with non-Latina black women (3.3). Prevalence of primary SS did not differ by race/ethnicity. Similar trends were observed when more restrictive case definitions were applied. CONCLUSION: Data from the MLSP revealed disparities among Manhattan residents in primary SS incidence and prevalence by sex and differences in primary SS incidence by race/ethnicity among women. These data also provided epidemiologic estimates for the major racial/ethnic populations in the US.
30878889 Medical data quality assessment: On the development of an automated framework for medical 2019 Apr Data quality assessment has gained attention in the recent years since more and more companies and medical centers are highlighting the importance of an automated framework to effectively manage the quality of their big data. Data cleaning, also known as data curation, lies in the heart of the data quality assessment and is a key aspect prior to the development of any data analytics services. In this work, we present the objectives, functionalities and methodological advances of an automated framework for data curation from a medical perspective. The steps towards the development of a system for data quality assessment are first described along with multidisciplinary data quality measures. A three-layer architecture which realizes these steps is then presented. Emphasis is given on the detection and tracking of inconsistencies, missing values, outliers, and similarities, as well as, on data standardization to finally enable data harmonization. A case study is conducted in order to demonstrate the applicability and reliability of the proposed framework on two well-established cohorts with clinical data related to the primary Sjögren's Syndrome (pSS). Our results confirm the validity of the proposed framework towards the automated and fast identification of outliers, inconsistencies, and highly-correlated and duplicated terms, as well as, the successful matching of more than 85% of the pSS-related medical terms in both cohorts, yielding more accurate, relevant, and consistent clinical data.
30776490 Geoepidemiology of Sjögren's syndrome in Latin America. 2019 Oct OBJECTIVE: To evaluate the geoepidemiology of Sjögren's syndrome (SS) in Latin America. METHODS: This was a three phase study in which original data from a Colombian cohort of patients with SS is presented, followed by a systematic review of Colombian and Latin American studies. Lastly, the geoepidemiology of SS in Latin America was assessed by comparing the clinical characteristics of the region with those of the rest of the world by means of a meta-analysis approach. RESULTS: Data from 2970 patients from Latin America and 18019 patients from Europe, North America and Asia were analyzed. Colombian patients have a lower age at disease onset than those from other Latin American countries and a higher rate of positivity of antinuclear antibodies and rheumatoid factor. A significant difference in the proportion of female patients in Latin America compared with Europe and North America was observed. The spectrum of disease in Latin American was similar to North American patients, while strong differences were noticed between Latin American and European and Asian patients. Noteworthy, a paucity of reports including African and African-descendent patients was observed. CONCLUSIONS: The clinical spectrum of SS differs between countries and continents. Genetic differences relying upon ancestry could explain these findings. However, environmental factors have proven to be important determinants in the development of autoimmune diseases (i.e., autoimmune ecology). Thus, ancestry and the autoimmune ecology should be considered in studies aimed to evaluate the geoepidemiology of SS and other autoimmune diseases.
33935441 Management of hypothyroidism by Kshara Basti (therapeutic enema)- A case report. 2019 Oct Hypothyroidism is emerging as a common health concern in India as well as worldwide. An autoimmune cause accounts for approximately 90% of adult hypothyroidism mostly due to Hashimoto's disease. This autoimmunity goes parallel with the theory of Ama (intermediatory product) in Ayurveda. A case of a 27-year-old female patient, presenting with pain in multiple joints, deformity in the right little finger, morning stiffness lasting for more than 3 h, reduced appetite, constipation, and lethargy, diagnosed with Amavata (rheumatoid arthritis), was subclinically diagnosed with hypothyroidism and treated with Deepana (stimulates digestion), Pachana (promots digestion) and Koshtha Shuddhi (mild purgation) for 5 days followed by Kshara Basti (therapeutic enema) for 5 days. Reduction in serum- thyroid-stimulating hormone (S. TSH) (31.1 mIU/ml to 16.6 mIU/ml) along with relief in clinical manifestations of the disease was the outcome. Koshtha Shuddhi followed by Kshara Basti has its efficacy in hypothyroidism, as it not only improved signs and symptoms but S.TSH level was reduced significantly. This case report proposes an innovative treatment modality for the management of hypothyroidism, which needs to be validated through a well-planned study on a large sample size.
31253169 Prostaglandin receptor EP4 expression by Th17 cells is associated with high disease activi 2019 Jun 28 BACKGROUND: Th17 cells are involved in the pathogenesis of ankylosing spondylitis (AS). However, the mechanism underlying enhanced Th17 cell accumulation in AS remains unknown. The prostaglandin E(2) receptor EP2/EP4 signaling pathway plays a critical role in the development of autoimmune Th17 cells. Interestingly, recent genome-wide association studies (GWAS) have identified five risk alleles for AS in PTGER4, the gene encoding for EP4. The aim of this study was to reveal a possible link between EP4 and disease activity in patients with AS. METHODS: Th17 cells from patients with AS were analyzed for the transcriptional expression of prostaglandin receptor genes by quantitative RT-PCR. Th17 cells from patients with rheumatoid arthritis (RA) and from healthy individuals served as controls. EP4 receptor expression in Th17 cells was assessed ex vivo by flow cytometry and by western blot. Functional analysis using EP4-specific agonists was performed to reveal how EP4 regulates Th17 cells. RESULTS: EP4 is significantly overexpressed in Th17 cells from patients with AS compared to Th17 cells from healthy individuals or patients with RA or psoriatic arthritis (PsA). EP4 upregulation is unique to Th17 cells and is not found in other CD4(+) T cell subsets. Specific activation of EP4 drives Th17 cell development and promotes EP4 expression in a positive feedback loop in AS but not in RA or PsA. Mechanistically, EP4 acts via upregulation of the interleukin-23 receptor (IL-23R), by suppressing the RORγt inhibitor FoxO1 and by enhancing STAT3 phosphorylation. Increased EP4 expression levels in Th17 cells from AS patients correlate with high disease activity as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 (r = 0.7591, p = 0.0016). CONCLUSIONS: EP4 is a potential marker of disease activity in patients with AS. Aberrant EP4 expression might contribute to pathogenic Th17 cell accumulation and represent a new target for the treatment of AS.
31092910 HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications. 2019 Jun Our understanding of the mechanisms underlying HLA associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HLA genotype with other genes and environmental risk factors in determining disease risk have been identified. This Review provides basic information on the genetics and molecular function of HLA molecules, as well as general features of HLA associations with disease. Evidence is discussed regarding the various peptide-dependent and peptide-independent mechanisms by which HLA alleles might contribute to the pathogenesis of three types of inflammatory arthritis: rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HLA allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and paediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HLA associations in developing personalized strategies for the treatment and prevention of these diseases.
31457045 The Effect of Human Recombinant Tumor Necrosis Factor Receptor-2 on Reducing Inflammatory 2019 Jan BACKGROUND: The tumor necrosis factor alpha (TNFα) is a cytokine that produced principally by monocyte/macrophages and T lymphocytes, respectively. TNFα is recognized as the primary mediator of immunity in inflammation reaction. One important application of Tumor Necrosis Factor Receptor 2 (TNFR2) is for the treatment of autoimmune diseases like rheumatoid arthritis (RA). OBJECTIVES: The aim of this study is to examine the therapeutic trace of the recombinant humanTNFR2 on collagen-induced arthritis (CIA) in mice. MATERIALS AND METHODS: CIA was created in 20 mice by immunization with bovine type II collagen (CII). After the mice were boosted on day 21, they were injected with the recombinant protein in test group (1 mg.kg-1) and assessed edema in paws and knee joints after two weeks. The quantities of inflammatory cytokines such as TNF-α, interleukin-1 beta (IL-β1), interleukin-6 (IL-6), and interleukin-10(IL-10) in serum were evaluated through enzyme-linked immunosorbent assay (ELISA) kit. In addition, the histopathology of joints sections was analyzed. RESULTS: The cytokines TNF-α, IL-1β, and IL-6 values in serum markedly decreased in groups treated with TNFR2 (P < 0.01-0.001). The results showed that treatment with TNFR2 significantly reduced edema in paws and joints (P < 0.01-0.001). CONCLUSIONS: Pathological investigations proved that administration of recombinant TNF receptor has blocked or protected joints from progressive damage. This study suggests that the anti-arthritic effectiveness of TNFR2 will repress the symptoms of rheumatoid arthritis. Moreover, it seems that TNFR2 is a strong candidate for the treatment of the RA disease.
31785384 Attenuation of oxidative stress in arthritic rats by ethanolic extract of Albizia procera 2020 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Albizia procera L. (Leguminosae) commonly known as Konda vagai in Tamil, is used for the treatment of stomach and intestinal disorders. A decoction of the bark is prescribed for rheumatism and haemorrhage. Traditionally, literature claims Albizia procera as a drug to have antirheumatic properties and hence used by Tribal for the management of chronic rheumatism. Consequently, the present study has been undertaken to illustrate the beneficial outcome of Albizia procera in adjuvant induced arthritic rat model with respect to its antioxidant and anti-inflammatory activities. AIM OF THE STUDY: The present study is aimed to investigate the oxidative stress and the expression of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. MATERIALS AND METHODS: Ethanolic bark extract was characterized by HPTLC analysis. Acute oral toxicity study was performed according to the OECD test guideline 423 - Acute toxic class method. The anti-inflammatory effect of ETBE (100, 200 mg/kg/day/p.o.) was evaluated in complete Freund's adjuvant induced arthritic rats using diclofenac as positive control (0.3 mg/kg/day/p. o.). Plasma levels of interleukins TNF- α, IFN-α, IL-2, IL-6, myeloperoxidase and Cathepsin D levels were measured to assess the inflammatory effect of ETBE extract of Albizia procera. Further, the effect of ETBE on superoxide dismutase (SOD), glutathione peroxidase (GPX), reduced glutathione (GSH) and lipid peroxidation (LPO) were assessed in plasma. RESULTS: HPTLC analysis showed the presence of 0.57% w/w of biochanin-A in ETBE. ETBE did not show any toxic signs up to 2000 mg/kg body weight. It exhibited the significant anti-inflammatory and antioxidant potential and did not show mortality up to 2000 mg/kg body weight. ETBE treatment significantly reduced the levels of TNF- α, IFN-α, IL-2, IL-6 and myeloperoxidase, and increased cathepsin D levels compared to vehicle treated animals. SOD, GSH and GPX levels were significantly restored to normal levels while LPO was significantly reduced at 200 mg/kg b. wt. Treated animals. Histopathological studies showed complete cartilage regeneration and near normal joint in ETBE treated arthritic rats. CONCLUSION: ETBE demonstrated potent anti-inflammatory activity by modulating the expression of inflammatory cytokines and restoring the antioxidant enzyme levels.
31036623 Association between inactivated influenza vaccine and primary care consultations for autoi 2019 Aug ObjectivesTo examine the association between inactivated influenza vaccine (IIV) administration and primary care consultation for joint pain, rheumatoid arthritis (RA) flare, corticosteroid prescription, vasculitis and unexplained fever in people with autoimmune rheumatic diseases (AIRDs). METHODS: We undertook within-person comparisons using self-controlled case-series methodology. AIRD cases who received the IIV and had an outcome of interest in the same influenza cycle were ascertained in Clinical Practice Research Datalink. The influenza cycle was partitioned into exposure periods (1-14 days prevaccination and 0-14, 15-30, 31-60 and 61-90 days postvaccination), with the remaining time-period classified as non-exposed. Incidence rate ratios (IRR) and 95% CI for different outcomes were calculated. RESULTS: Data for 14 928 AIRD cases (69% women, 80% with RA) were included. There was no evidence for association between vaccination and primary care consultation for RA flare, corticosteroid prescription, fever or vasculitis. On the contrary, vaccination associated with reduced primary care consultation for joint pain in the subsequent 90 days (IRR 0.91 (95% CI 0.87 to 0.94)). CONCLUSION: This study found no evidence for a significant association between vaccination and primary care consultation for most surrogates of increased disease activity or vaccine adverse-effects in people with AIRDs. It adds to the accumulating evidence to support influenza vaccination in AIRDs.
31431516 FM0807 decelerates experimental arthritis progression by inhibiting inflammatory responses 2019 Sep 30 BACKGROUND: Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analog FM0807 (curcumin salicylate monoester, 2-hydroxy-, 4-[(1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl]-2-methoxyphenyl ester) on experimental RA and investigate its possible mechanisms of action. METHOD: Rats with Freund's complete adjuvant (FCA)-induced arthritis (AIA) were administered aspirin (0.1 mmol.kg(-1)), curcumin (0.1 mmol.kg(-1)), FM0807 (0.1, 0.2 mmol.kg(-1)) and vehicle via gastric gavage, from days 7 to 21, once daily. The hind paw volume and arthritis index (AI) were measured, and radiographic and histological examinations were performed. Twenty-one days later, the animals were killed and left ankle joints were removed to measure protein expression of the elements of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway by Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) was employed to measure synovial fluid levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10. RESULTS: Compared with AIA group, FM0807 reduced the AI and swelling of the injected hind paw in a dose-dependent manner, and inhibited increases in inflammatory cell infiltration, pannus formation and cartilage destruction. FM0807 also potently attenuated the increase in the expression of inflammatory factors TNF-α, IL-6 and IL-1β in synovial fluid, while IL-10 levels were also elevated. FM0807 significantly suppressed phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK) 1/2 (JNK1/2), p38MAPK, inhibitor of NF-κB kinase (IKK), IκB and NF-κB p65 protein, (all P<0.05), which displayed more potential effects compared with those of the aspirin and curcumin groups. CONCLUSION: FM0807 exerts its therapeutic effects on RA by inhibiting cartilage degeneration. FM0807 treatment might be an effective therapeutic approach for RA.
30561748 Is early-onset primary Sjögren's syndrome a worse prognosis form of the disease? 2019 Jul 1 OBJECTIVES: Onset of primary SS is usually between 40 and 60 years of age, with severe systemic complications in 15% of cases. We sought to determine whether early-onset disease is related to a specific phenotype and if it is predictive of a poor outcome. METHODS: Biological and clinical data from 393 patients recruited in the ASSESS cohort, a French multicentre prospective cohort, were compared according to age at diagnosis. RESULTS: Fifty-five patients had early-onset disease, defined as age ⩽35 years at diagnosis, and presented a significantly higher frequency of salivary gland enlargement (47.2% vs 33.3%, P = 0.045), adenopathy (25.5% vs 11.8%, P = 0.006), purpura (23.6% vs 9.2%, P = 0.002) and renal involvement (16.4% vs 4.4%, P = 0.003). They had a higher frequency of hypergammaglobulinaemia (60.8% vs 26.6%, P < 0.001), RF positivity (41.5% vs 20.2%, P < 0.001), low C3 level (18.9% vs 9.1%, P = 0.032), low C4 level (54.7% vs 40.2%, P = 0.048) and autoantibodies [84.6% with anti-SSA vs 54.4% (P < 0.001) and 57.7% with anti-SSB vs 29.7% (P < 0.001)]. The change in ESSDAI scores between baseline and the 5-year follow-up was significantly different (P = 0.005) with a trend for worsening in the early-onset group (0.72, P = 0.27) and a significant improvement in the later onset group (-1.27, P < 0.0001). CONCLUSION: Early-onset primary SS is associated with a specific phenotype defined by clinical and biological features known to be predictive factors of severe systemic disease. Interestingly, we showed a different evolution of the ESSDAI score depending on the age at disease onset, patients with early-onset disease tending to worsen over time.
33365965 Characterization of the complete chloroplast genome of Ephedra sinica Stapf (Ephedraceae), 2019 Oct 1 Ephedra sinica Stapf is a traditional Chinese medicine of Ephedraceae in China, which contains many chemicals, such as ephedrine and pseudoephedrine, flavonoids, polysaccharides, phenolic compounds, and proanthocyanidins. It shows significant activity in asthma, fever, rheumatoid arthritis, and also promotes diuresis and sweat.
30883600 Correction: Epidemiology and treatment patterns of rheumatoid arthritis in a large cohort 2019 [This corrects the article DOI: 10.1371/journal.pone.0208240.].
31116832 The Effects of Systemic Diseases and Medications on Implant Osseointegration: A Systematic 2019 Suppl Since their development, dental implants have become one of the most common procedures to rehabilitate patients with single missing teeth or fully edentulous jaws. As implants become more mainstream, determining the factors that affect osseointegration is extremely important. Medical risk factors identified to negatively affect osseointegration include diabetes and osteoporosis. However, other systemic conditions and medications that interfere with wound healing have not been as widely investigated. The aim of this systematic review was to evaluate the effect of systemic disorders including diabetes and osteoporosis on implant osseointegration. The aim was also to evaluate the effect of other diseases, such as neurocognitive diseases, cardiovascular disease, human immunodeficiency virus (HIV), hypothyroidism, rheumatoid arthritis, and medications, such as selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), and antihypertensives. Although the literature does not demonstrate that diabetes negatively affects implant osseointegration, most studies focus on well-controlled diabetics and the use of prophylactic antibiotics. In addition, studies have shown increased long-term bone and soft tissue complications. For osteoporosis, recent studies and reviews also fail to demonstrate a lower osseointegration rate. However, caution must be exercised in these patients due to the risk for osteonecrosis of the jaws (ONJ), especially in patients with bone malignancies. There is also no direct evidence that patients with HIV, cardiovascular disease, neurologic disorders, hypothyroidism, or rheumatoid arthritis have a decreased rate of implant osseointegration. However, some preliminary evidence suggests that medications such as SSRIs or PPIs may have a negative effect on implant osseointegration. These studies are fairly recent and must be validated with continuous research. Moreover, disease control, concomitant medications, and other comorbidities complicate implant osseointegration and must guide our treatment approaches and clinical guidelines.
30989962 [Mufangji Decoction formula tracing and its effect on emergency and severe cases]. 2019 Jan Mufangji Decoction is a famous herbal formula from Synopsis of Golden Chamber. However,it is easy to be misunderstood due to so its unique compatability. The syndromes treated by Mufangji Decoction included the following aspects:(1) in terms of modern medicine,it could be used to treat acute and chronic heart failure,heart failure aggravated by lung infection,chronic obstructive pulmonary disease acute episode,pulmonary heart disease,bilateral pleural effusion,acute attack of gout,rheumatic fever,rheumatoid arthritis,and rheumatoid arthritis;(2) in terms of symptoms,it could be used to treat asthma,chest tightness,wheeze impacting prostration and dyspnea impacting sitting posture; gastric distention; dark face,cyanotic,and mitral valvular face; edema of head and extremities; dry mouth,thirsty,unwilling to wear thick clothes,intolerance of heat,and irritable; fatigue,shortness of breath,poor appetite,constipation,less urine,yellow color,poor response to diuretics,and diuretic resistance; fast heart rate,which is hard to be controlled by Western medicine and has no response to Zhenwu Decoction; dark red tongue,dry tongue with yellow fur,rapid pulse,or deep tight pulse. In emergency and severe cases,Yang deficiency and fluid retention are normal syndromes of heart failure,while Yang deficiency,fluid retention,and heat are metamorphic syndromes of heart failure,which possessed complex mechanisms of pathophysiology; the mechanisms of Shaoyin heat-conversion syndrome is similar to Yang deficiency,fluid retention,and heat syndrome; the reason of application of gypsum in Mufangji Decoction shall be further studied; the " empty" and " real" in modified Mufangji Decoction are physical signs,rather than pathogenesis.
30952398 Tools and Methods for Real-World Evidence Generation: Pragmatic Trials, Electronic Consent 2019 May Real-world evidence requires use of new tools and methods to support efficient evidence generation. Among those tools are pragmatic trials, utilization of central/single institutional review board and electronic consent, and data linkages between diverse types of data sources (eg, a trial or registry to administrative claims or electronic medical record data). This article reviews these topics in the context of describing several exemplar use cases specific to rheumatology and provides perspective regarding both the promise and potential pitfalls in using these tools and approaches.
30547186 MicroRNA-124 inhibits TNF-α- and IL-6-induced osteoclastogenesis. 2019 Apr Receptor activator for nuclear factor κB ligand (RANKL)-independent osteoclastogenic pathway was reported recently. MicroRNA (miR)-124 has been known to suppress RANKL-dependent osteoclastogenesis by inhibiting NFATc1 expression. However, whether miR-124 regulates a RANKL-independent pathway has not been elucidated. In this study, we examined whether a RANKL-independent pathway is regulated by miR-124 in addition to the RANKL-dependent one. Using osteoclastogenic culture and pit-formation assay, we found that a miR-124 mimic inhibited osteoclastogenesis in mouse bone marrow-derived macrophages stimulated by TNF-α, IL-6, and M-CSF in the presence of osteoprotegerin. We also showed that the expression levels of osteoclast-specific genes and NFATc1 protein were suppressed in the miR-124 mimic-transfected cells by performing quantitative-polymerase chain reaction and western blotting. Our results indicate that miR-124 is important in inhibiting both RANKL-dependent and -independent osteoclast differentiation by suppressing NFATc1-mediated pathway.
30871019 Association of PTPN22 1858C/T Polymorphism with Autoimmune Diseases: A Systematic Review a 2019 Mar 12 The 1858T allele in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) locus shows one of the strongest and most consistent genetic associations with autoimmune diseases. We synthesized all meta-analyses reporting a genetic association of the PTPN22 1858T C/T polymorphism with autoimmune diseases. This work examined their validity to discover false positive results under Bayesian methods. We conducted a PubMed search to identify relevant publications and extracted the respective results, published until 30 November 2018. In observational studies, the associations of 1858 C/T genetic variant were noteworthy for 12 autoimmune or autoimmunity-related diseases (rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, juvenile idiopathic arthritis, Crohn's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, vitiligo, Graves' disease, myasthenia gravis, Addison's disease, giant cell arteritis, and endometriosis). In contrast, we could not confirm the noteworthiness for eight diseases (systemic sclerosis, psoriasis, Behçet's disease, autoimmune thyroid disease, alopecia areata, Sjögren's syndrome, inflammatory bowel disease, and ankylosing spondylitis). From the meta-analysis of genome-wide association studies (GWAS) with a p-value < 5 × 10(-8), findings verified noteworthiness for all autoimmune diseases (psoriatic arthritis, myasthenia gravis, juvenile idiopathic arthritis and rheumatoid arthritis). The results from meta-analysis of GWAS showing a p-value ranging between 0.05 and 5 × 10(-8) were noteworthy under both Bayesian approaches (ANCA-associated vasculitis, type 1 diabetes mellitus, giant cell arteritis and juvenile idiopathic arthritis). Re-analysis of observational studies and GWAS by Bayesian approaches revealed the noteworthiness of all significant associations observed by GWAS, but noteworthiness could not be confirmed for all associations found in observational studies.