Protective effect of Salvia miltiorrhiza in rheumatoid arthritis patients: A randomized, single-blind, placebocontrolled trial

Purpose: To study the protective effect of Salvia miltiorrhiza (SM) against rheumatoid arthritis (RA) in RA patients.Methods: Sixty RA patients were divided into two groups: SM (n = 30) and placebo (n =30) groups given SM at a dose of 250 mg/kg (3 capsules/day), and placebo (3 capsule/day), respectively, for 12 weeks. Patient responses based on American College of Rheumatology (ACR), health assessmentquestionnaire (HAQ) score, and global assessment of disease (GAD) were recorded. Moreover, Disease Activity Score (DAS) 28, pain score (visual analogue score, VAS), rheumatoid factor (Rh factor), and inflammatory cytokines (markers) were determined.Results: After 12 weeks of intervention with SM, ACR20 (30 %)/ACR50 patient response (13.3%, i.e., score for swelling and tenderness of joints), was significantly improved. There were considerable reductions in GAD, HAQ, DAS 28, pain score (VAS), and levels of erythrocyte sedimentation rate(ESR), acute phase reaction protein (CRP), Rh factor (IgM) and inflammatory cytokines (IL-1β, IL-6 and TNF-α), when compared to placebo (p < 0.01). Treatment with SM produced milder adverse effects than treatment with placebo (p < 0.01).Conclusion: Overall, SM produces better anti-RA effect than placebo by significantly altering ACR patient response, reducing GAD, HAQ, DAS 28 scores, Rh factor, ESR, CRP and inflammatory cytokines in RA patients. However, a large-scale clinical trial is needed before SM can be recommended for combating RA and its related symptoms. Keywords: Salvia miltiorrhiza, Rheumatoid arthritis, DAS 28, Adverse effec

Clinical outcomes of S2 Alar-Iliac screw technique in the treatment of severe spinal sagittal imbalance: a retrospective 2-year follow-up study

Background: The treatment of adult spinal deformity (ASD) remains a significant challenge, especially in elderly patients. This study aimed to evaluate the outcomes of the S2AI screw technique in the treatment of severe spinal sagittal imbalance with a minimum 2-year follow-up.Methods: From January 2015 to December 2018, 23 patients with severe degenerative thoracolumbar kyphosis who underwent placement of S2AI screws for long segment fusion were retrospectively reviewed. Patients were divided into group A (no mechanical complications, 13 cases) and group B (with mechanical complications, 10 cases) according to the occurrence of mechanical complications at the last follow-up. Radiographic parameters were compared between groups preoperatively, 1 month postoperatively and at the last follow-up. Risk factors for mechanical complications were analyzed.Results: The incidence of mechanical complications was 43.5% and the revision rate was 17.4%. At 1 month postoperatively, sagittal correction was better in group A than in group B (p<0.05). The area under the curve for predicting mechanical complications of sacral slope (SS), lumbar lordosis (LL), PI (pelvic incidence)-LL at 1 month postoperatively were 0.762 (p=0.035), 0.896 (p=0.001) and 0.754 (p=0.041) respectively and the best cut-off values were 24.1°, 32.8°and 12.0°. The sagittal correction of both groups was partially lost at the last follow-up.Conclusions: A high incidence of mechanical complications was observed in long-segment corrective surgery with the S2AI screw technique for severe spinal sagittal imbalance. Inadequate sagittal correction is a risk factor for the development of mechanical complications.

Increased concentrations of soluble B7-H3 and interleukin 36 in bronchoalveolar lavage fluid of Children with Mycoplasma pneumoniae pneumonia

Supporting data. (XLS 58 kb

Highly efficient urea oxidation via nesting nano nickel oxide in eggshell membrane-derived carbon

Here, we reported a strategy of using an eggshell membrane to produce hierarchically porous carbon as a low-cost substrate for synthesizing a nano-nickel oxide catalyst (C@NiO), which can effectively turn biowaste—urea—into energy through an electrochemical approach. The interwoven carbon networks within NiO led to highly efficient urea oxidation due to the strong synergistic effect. The as-prepared electrode only needed 1.36 V versus reversible hydrogen electrode to realize a high efficiency of 10 mA cm–2 in 1.0 M KOH with 0.33 M urea and delivered an even higher current density of 25 mA cm–2 at 1.46 V, which is smaller than that of the porous carbon and commercial Pt/C catalyst. Benefiting from theoretical calculations, Ni(III) active species and the porous carbon further enabled the electrocatalyst to effectively inhibit the “CO2 poisoning” of electrocatalysts, as well as ensuring its superior performance for urea oxidation

Polydopamine nanoparticles for treatment of acute inflammation-induced injury

Nanotechnology-mediated anti-inflammatory therapy is emerging as a novel strategy for treatment of inflammation-induced injury. However, one of the main hurdles for these anti-inflammatory nano-drugs is their potential toxic side effects in vivo. Herein, we uncovered that polydopamine (PDA) nanoparticles with structure and chemical properties similar to melanin, a natural bio-polymer, displayed significant anti-inflammation therapeutic effect on acute inflammation-induced injury. PDA with enriched phenol groups functioned as a radical scavenger to eliminate reactive oxygen species (ROS) generated during inflammatory responses. As revealed by in vivo photoacoustic imaging with a H2O2-specific nanoprobe, PDA nanoparticles remarkably reduced intracellular ROS levels in murine macrophages challenged with either H2O2 or lipopolysaccharide (LPS). The anti-inflammatory capacity of PDA nanoparticles was further demonstrated in murine models of both acute peritonitis and acute lung injury (ALI), where diminished ROS generation, reduced proinflammatory cytokines, attenuated neutrophil infiltration, and alleviated lung tissue damage were observed in PDA-treated mice after a single dose of PDA treatment. Our work therefore presents the great promise of PDA nanoparticles as a biocompatible nano-drug for anti-inflammation therapy to treat acute inflammation-induced injury

TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ

Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7-/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7-/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7

Reduced expression of lamin A/C correlates with poor histological differentiation and prognosis in primary gastric carcinoma

<p>Abstract</p> <p>Background</p> <p>Lamin A/C is very important in DNA replication, RNA dependent transcription and nuclear stabilization. Reduced or absent lamin A/C expression has been found to be a common feature of a variety of different cancers. To investigate the role of lamin A/C in gastric carcinoma (GC) pathogenesis, we analyzed the correlations between the lamin A/C expression level and clinicopathological factors and studied its prognostic role in primary GC.</p> <p>Methods</p> <p>The expression of lamin A/C at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Lamin A/C expression and its prognostic significance were investigated by performing immunohistochemical analysis on a total of 126 GC clinical tissue samples.</p> <p>Results</p> <p>Both lamin A/C mRNA and protein expression were downregulated in the majority of tumours compared with corresponding normal gastric tissues (<it>p </it>= 0.011 and <it>p </it>= 0.036, respectively). Real time RT-PCR further validated that downregulation of lamin A/C is associated with poor histological differentiation (r = 0.438, <it>p </it>= 0.025). The immunohistochemical staining showed an evident decrease of lamin A/C expression in 55.6% (70/126) GC cases. Importantly, the negative lamin A/C expression correlated strongly with histological classification (r = 0.361, <it>p </it>= 0.034). Survival analysis revealed that patients with lamin A/C downregulation have a poorer prognosis (<it>p </it>= 0.034). In addition, lamin A/C expression was found to be an independent prognostic factor by multivariate analysis.</p> <p>Conclusion</p> <p>Data of this study suggest that lamin A/C is involved in the pathogenesis of GC, and it may serve as a valuable biomarker for assessing the prognosis for primary GC.</p

Advanced NSCLC Patients With EGFR T790M Harboring TP53 R273C or KRAS G12V Cannot Benefit From Osimertinib Based on a Clinical Multicentre Study by Tissue and Liquid Biopsy

BackgroundNon-small cell lung cancer (NSCLC) patients treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) almost always acquire resistance, and the development of novel techniques analyzing circulating tumor DNA (ctDNA) have made it possible for liquid biopsy to detect genetic alterations from limited amount of DNA with less invasiveness. While a large amount of patients with EGFR exon 21 p.Thr790 Met (T790M) benefited from osimertinib treatment, acquired resistance to osimertinb has subsequently become a growing challenge.MethodsWe performed tissue and liquid rebiopsy on 50 patients with EGFR-mutant NSCLC who acquired resistance to first-generation EGFR-TKIs. Plasma samples underwent droplet digital PCR (ddPCR) and next-generation sequencing (NGS) examinations. Corresponding tissue samples underwent NGS and Cobas® EGFR Mutation Test v2 (Cobas) examinations.ResultsOf the 50 patients evaluated, the mutation detection rates of liquid biopsy group and tissue biopsy group demonstrated no significant differences (41/48, 85.4% vs. 44/48, 91.7%; OR=0.53, 95% CI=0.15 to 1.95). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 78.3% (36/46, 95% CI=0.39 to 2.69). Moreover, our results showed that almost half of the patients (46%, 23/50) resistant to first-generation EGFR-TKI harbored p.Thr790 Met (T790M) mutation. 82.6% (19/23) of the T790M positive patients were analyzed by liquid biopsy and 60.9% (14/23) by tumor tissue sequencing. Meanwhile, a wide range of uncommon mutations was detected, and novel mechanisms of osimertinib resistance were discovered. In addition, 16.7% (2/12) of the T790M positive patients with either TP53 R237C or KRAS G12V failed to benefit from the subsequent osimertinib treatment.ConclusionOur results emphasized that liquid biopsy is applicable to analyze the drug resistance mechanisms of NSCLC patients treated with EGFR-TKIs. Moreover, we discovered two uncommon mutations, TP53 R273C and KRAS G12V, which attenuates the effectiveness of osimertinib