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Objective: To investigate whether there is a difference in the efficacy of intra-articular injection of tumor necrosis factor (TNF) inhibitor and triamcinolone acetonide (HA) in rheumatoid arthritis (RA) patients with recurrent synovitis after the first intra-articular injection of HA. Methods: RA patients who relapsed 12 weeks after the first HA treatment were enrolled in this study. After joint cavity extraction, recombinant human TNF receptor-antibody fusion protein (TNFR:FC) (25 mg or 12.5 mg) or HA (1 ml or 0.5 ml) was injected then. The changes in the visual analog scale (VAS), joint swelling index, and joint tenderness index before and 12 weeks after reinjection were compared and analyzed. The changes in synovial thickness, synovial blood flow, and fluid dark zone depth before and after reinjection were observed by ultrasound. Results: Forty-two RA patients were enrolled, including 11 males and 31 females, with an average age of 46.79 ± 12.61 years and an average disease duration of 7.76 ± 5.44 years. After 12 weeks of intra-articular injection of HA or TNFR:FC, the VAS scores were significantly lower than those before treatment (P < 0.01). After 12 weeks of injection, the scores of the joint swelling index and tenderness index in both groups were significantly decreased compared with those before treatment. There was no significant difference in synovial thickness under ultrasound in the HA group before and after injection, while the synovial thickness in the TNFR:FC group was significantly improved after 12 weeks (P < 0.01). After 12 weeks of injection, the grade of synovial blood flow signal in both groups decreased significantly compared with that before treatment, especially in the TNFR:FC group. After 12 weeks of injection, the depth of the liquid dark area under ultrasound decreased significantly in the HA group and TNFR:FC group compared with that before treatment (P < 0.01). Conclusion: Intra-articular injection of a TNF inhibitor is an effective method for the treatment of recurrent synovitis after conventional hormone therapy. Compared with HA treatment, it can reduce synovial thickness. Key Points • Intra-articular injection of a TNF inhibitor is an effective method for the treatment of recurrent synovitis after conventional hormone therapy. • Compared with HA treatment, intra-articular injection of biological agents combined with glucocorticoids can not only relieve joint pain but also significantly inhibit joint swelling. • Compared with HA treatment, intra-articular injection of biological agents combined with glucocorticoids cannot only improve synovial inflammation but also inhibit synovial proliferation. • For the treatment of refractory RA synovitis, biological agents combined with glucocorticoid injection are an effective and safe option. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a special type of pulmonary parenchymal disease, with chronic, progressive, fibrosis, and high mortality. There is a lack of safe, effective, and affordable treatment methods. Qilongtian (QLT) is a traditional Chinese prescription that is composed of Panax notoginseng, Earthworm, and Rhodiola, and shows the remarkable clinical curative effect of PF. However, the mechanism of QLT remains to be clarified. Therefore, we studied the effectivity of QLT in treating Bleomycin (BLM) induced PF mice. 36 C57BL/6 J mice were randomized into the control group, the model group, the low-, medium- and high-dose QLT group, and Pirfenidone group. After establishing a model of pulmonary fibrosis in mice, the control and model groups were infused with a normal saline solution, and the delivery group was infused with QLT. Pulmonary function in the mice from each group was detected. Pulmonary tissue morphologies and collagen deposition were stained by HE and Masson. The content of hydroxyproline (HYP) was detected by alkaline hydrolysis and the mRNA and protein expression of related genes in pulmonary tissues were detected by using q-PCR, ELISA, and Western blot. Our studies have shown that QLT significantly reduced the inflammatory injury, hydroxy-proline content, and collagen deposition of pulmonary tissue in BLM-induced PF mice and down-regulated the cytokine related to inflammation and fibrosis and PF expression on the mRNA and protein level in PF mice. To identify the mechanism of QLT, the Transcriptome was measured and the IL-17 signal pathway was screened out for further research. Further studies indicated that QLT reduced the mRNAs and protein levels of interleukin 17 (IL-17), c–c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 5 (CXCL5), fos-like antigen 1 (FOSL1), matrix metalloproteinase-9 (MMP9), and amphiregulin (AREG), which are inflammation and fibrosis-related genes in the IL-17 signal pathway. The results indicated that the potential mechanism for QLT in the prevention of PF progression was by inhibiting inflammation resulting in the IL-17 signal pathway. Our study provides the novel scientific basis of QLT and represents new therapeutics for PF in clinical. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a chronic, progressive, and fibrotic interstitial lung disease with a high mortality rate. Qi-Long-Tian (QLT) capsule is an herbal formula with great potential for antifibrotic effects, consisting of San Qi (Notoginseng Radix et Rhizoma), Di Long [Pheretima aspergillum (E. Perrier)], and Hong Jingtian (Rhodiolae Crenulatae Radix et Rhizoma), and has been used in clinical practice for many years. To explore the relationship between the effects of Qi-Long-Tian capsule and gut microbiota of PF mice, pulmonary fibrosis model were established by tracheal drip injection of bleomycin. Thirty-six mice were randomly divided into 6 groups: control group (control), model group (model), QLT capsule low dose group (QL), QLT capsule medium dose group (QM), QLT capsule high dose group (QH), and pirfenidone group (PFD). After 21 days of treatment, after pulmonary function tests, the lung tissues, serums, and enterobacterial samples were collected for further analysis. HE staining and Masson’s staining were used to detect changes as the main indicators of PF in each group, and the expression of hydroxyproline (HYP) related to collagen metabolism was detected by and alkaline hydrolysis method. qRT-PCR and ELISA were used to detect the mRNA and protein expressions of pro-inflammatory factors include interleukin 1β (IL-1β), interleukin 6 (IL-6), transforming growth factor β1 (TGF-β1), tumor necrosis factor α (TNF-α) in lung tissues and serums, and the inflammation-mediating factors include tight junction protein (ZO-1, Claudin, Occludin). ELISA was used to detect the protein expressions of secretory immunoglobulin A (sIgA), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS) in colonic tissues. 16sRNA gene sequencing was used to detect changes in the abundance and diversity of intestinal flora in the control, model, and QM groups, to search for differential genera, and analyze the correlation with inflammatory factors. QLT capsule effectively improved the status of pulmonary fibrosis and reduced HYP. In addition, QLT capsule significantly reduced the abnormal levels of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, and TGF-β in lung tissue and serum, while improving the levels of pro-inflammatory related factors ZO-1, Claudin, Occludin, sIgA, SCFAs, and reducing LPS in the colon. The comparison between the alpha diversity and beta diversity in enterobacteria suggested that the composition of the gut flora in the control, model, and QLT capsule groups were different. QLT capsule significantly increased the relative abundance of Bacteroidia (which might limit the onset of inflammation) and decreased the relative abundance of Clostridia (which might promote inflammation). In addition, these two enterobacteria were closely associated with pro-inflammatory-related indicators and pro-inflammatory factors in PF. All these results suggest that QLT capsule intervenes in pulmonary fibrosis by regulating the differential genera of intestinal flora, increasing immunoglobulin secretion, repairing the intestinal mucosal barrier, reducing LPS entry into the blood, and decreasing inflammatory factor secretion in the serum, which in turn alleviates pulmonary inflammation. This study clarifies the therapeutic mechanism of QLT capsule in PF and provides a theoretical basis for it. It provides a theoretical basis for its further clinical application. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Qiang Zhang, Ting Luo and Dezheng Yuan. Reference 1 Zhang, Q, Luo, T, Yuan, D, Fu, Y, Yuan J. Mechanism study of Qilongtian on pulmonary fibrosis in bleomycin model mice. [Extracted from the article]

A series of acetato-bridged [C^X]-type (C = aryl carbanion, X = N, P) palladacycles ( 1- 5) of the general formula [Pd(μ-CHCOO)(C^X)] were synthesized as metal precursors via slightly modified procedures. However, in the case of complex 5 with Dpbp (Dpbp = 2′-(diphenylphosphino-κ P)[1,1′-biphenyl]-2-yl-κ C) as the supporting C^P ligand, an unexpected dinuclear complex [Pd(μ-CO)(Dpbp)] ( 6) was obtained as a by-product and structurally determined by X-ray crystallography. The reactions of complexes 1- 4 with 2-(diphenylphosphino)benzoic acid conveniently afforded four carboxylate-functionalized phosphine complexes [Pd(C^N)(Dpb)] (Dbp = 2-(diphenylphosphino-κ P)benzoato-κ O, 7- 10), two of which ( 9/ 10) are newly synthesized in the present work and have been fully characterized. A comparative catalytic study revealed that complex [Pd(Ppy)(Dpb)] ( 7) (Ppy = 2-(2-pyridinyl-κ N)phenyl-κ C) is the best performer in Suzuki cross-couplings in HO. In addition, complex 7 exhibits much better catalytic activity compared to the non-functionalized phosphine equivalent [Pd(OAc)(PPh)(Ppy)] ( 11), which clearly indicates the superiority of incorporating a carboxylate-functionalized phosphine ligand into the palladacycles. A preliminary mechanistic study uncovered a different precatalyst initiation pathway compared to other known analogues of catalyst precursors. [ABSTRACT FROM AUTHOR]

This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated Proteobacteria, Firmicutes, and Bacteroidetes in the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas, Sphingobium, Lactobacillus, Rhizobium, and Acinetobacter, thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases. [ABSTRACT FROM AUTHOR]

Silicosis is a fatal pulmonary fibrotic disorder characterized by accumulation of fibroblasts and myofibroblasts and deposition of extracellular matrix proteins. MiR-449a is a potential mediator of many cellular processes, including cell proliferation, differentiation, and apoptosis. We hypothesized that miR-449a may play a crucial role in the progression of pulmonary fibrogenesis. Here, we described miR-449a as a new autophagy-regulated miRNA. Importantly, miR-449a expression was significantly decreased in lung tissues of mice with silica treatment, and it was similarly expressed in NIH-3T3 and MRC-5 cells stimulated with TGF-β1. The activity of autophagy was inhibited in fibrotic lung tissues and TGF-β1-treated fibroblasts. To investigate the potential effect of miR-449a, we overexpressed miR-449a in mouse models and found that miR-449a significantly reduced both the distribution and severity of lung lesions induced by silica. In addition, miR-449a was observed to induce the activity of autophagy in vivo and in vitro. Notably, Bcl2 was identified as a target of miR-449a. Bcl2 levels were decreased in NIH-3T3 cells upon miR-449a overexpression. Indeed, the Bcl2 3′ UTR contained functional miR-449a responsive sequences. Furthermore, TGF-β1 was observed to increase the expression of Bcl2 via the MAPK/ERK pathway. These results suggest that miR-449a is an important regulator of autophagy, as well as a novel endogenous suppressor of pulmonary fibrosis. Key message: [ABSTRACT FROM AUTHOR]