The association of an elevated Th/Ts ratio and lupus anticoagulant with symptomatic osteonecrosis in systemic lupus erythematosus patients.

Objective: This study aimed to assess the risk factors for symptomatic osteonecrosis (ON) in systemic lupus erythematosus (SLE) and identify clinical characteristics and laboratory markers for predicting symptomatic ON occurrence in SLE patients. Methods: Seventy (6.0%) of 1175 SLE patients diagnosed with symptomatic ON were included in this study. An equal number of SLE patients without symptomatic ON, matched in terms of age and gender, were enrolled in the control group. Clinical symptoms, routine laboratory examinations, lymphocyte subsets, and treatments of these patients were retrospectively reviewed and compared between the two groups. Logistic regression analysis was employed to identify risk factors associated with symptomatic ON in SLE. Results: Among the 70 cases in the symptomatic ON group, 62 (88.6%) patients experienced femoral head necrosis, with bilateral involvement observed in 58 patients. Bone pain was reported in 32 cases (51.6%), and 19 cases (30.6%) presented with multiple symptoms. Univariate analysis revealed significant differences between the two groups in various factors, including disease duration (months), cumulative steroid exposure time, history of thrombosis, neurological involvement, the number of affected organs, myalgia/myasthenia, and the use of medications such as glucocorticoids, immunosuppressants, aspirin, and statins (P<0.05). Moreover, lupus anticoagulant (LA) levels were significantly higher in the symptomatic ON group than in the control group (P<0.05). Furthermore, notable distinctions were observed in peripheral blood immune cells, including an elevated white blood cell count (WBC), a decreased percentage of Ts cells (CD3+CD8+), and an elevated Th/Ts ratio. Logistic regression analysis revealed that a history of thrombosis, LA positivity, and an elevated Th/Ts ratio remained positive factors associated with symptomatic ON (P<0.05). Conclusion: Decreased Ts cells and changes in the T lymphocyte subset play an important regulatory role in the development of symptomatic ON. A history of thrombosis and LA are associated with an increased probability of symptomatic ON in SLE and may serve as potential predictors.

Synergistic neuroprotective effect of saikosaponin A and albiflorin on corticosterone-induced apoptosis in PC12 cells via regulation of metabolic disorders and neuroinflammation.

BACKGROUND: Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanisms are still unknown. METHODS AND RESULTS: The corticosterone-induced PC12 cells apoptosis model was employed to assess the neuroprotective effects of SSA and AF, and the synergistic effect was analyzed using three mathematical models. Meanwhile, cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites than a single agent and possessed a stronger adjustment effect on metabolites. The TCA cycle was regulated by SSA and AF via improving mitochondrial function. The purine metabolism was regulated by SSA via inhibition xanthine oxidase activity and the glutamate metabolism was regulated by AF via inhibition glutaminase activity. Moreover, the oxidative stress induced by the purine metabolism was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression. CONCLUSIONS: This study for the first time demonstrated the synergistic neuroprotective effects of SSA and AF, and the synergistic mechanisms were involved in metabolic disorders regulation and neuroinflammation inhibition.

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.

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.