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Refereed/Peer-reviewed P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4+ and CD8+ T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA.

To explore the diagnosis and treatment of xanthogranulomatous prostatitis.A 75-year-old man presented with a 3-month history of difficult urination and frequent micturition, which was exacerbated for 2 days. Digital rectal examination indicated an enlarged prostate size of II degrees with hard texture but no tenderness. Serum total PSA was 172.5 microg/L. TRUS revealed 200 ml of post-micturition residual urine, thickened bladder wall, prostate size of 4.3 cm x 3.8 cm x 5.0 cm and no isochrones. MRI showed an enlarged prostate gland, with marked enlargement of the central zones and low-signal intensity of the peripheral gland, part of the prostate gland protruding to the bladder with no clear dividing line. It was diagnosed as prostate cancer initially, and confirmed by needle biopsy.Histopathological examination revealed large numbers of "foamy macrophages" in the lesion, with a few multinucleated giant cells, leukocytes, mononuclear, plasmocytes and fibroplasia. Immunohistochemistry showed CD68 (+) and PSA (-). The patient was treated with oral Tamsulosin and glucocorticoid and by temporary catheterization, and followed up for 20 months. Urination symptoms began to alleviate and serum PSA to decrease at 4 months. The PSA level was 9.2 microg/L at 13 months and 3.6 microg/L at 17 months.Xanthogranulomatous prostatitis is a rare clinically, which can be confirmed by histopathological examination. It is treated mainly by supportive therapy and, for the cases with severe lower urinary tract obstruction, TURP can be employed. Follow-up must be performed by possible examination of PSA and necessary needle biopsy of the prostate.