Fine particulate matter (PM_2.5) poses a significant global environmental health threat and is closely associated with diseases across multiple organ systems. This review systematically summarizes the toxic effects and underlying mechanisms of PM_2.5 in the respiratory, cardiovascular, nervous, immune, endocrine, digestive, and genitourinary systems. Key pathogenic processes involve shared pathways such as oxidative stress, inflammatory responses, endoplasmic reticulum stress, autophagy, and apoptosis, along with the activation of system-specific signaling networks. The complex composition and notable spatiotemporal variability of PM_2.5 present challenges for assessing its health risks and clarifying its mechanisms. Moving forward, integrating multi-omics and molecular epidemiology approaches will be essential to unravel its multi-system pathogenic networks and support the development of effective intervention strategies.

Background: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disorder characterized by osteoarticular and cutaneous manifestations. While tumor necrosis factor-alpha (TNF-α) inhibitors such as adalimumab are increasingly used for refractory cases, some patients exhibit inadequate response. Janus kinase (JAK) inhibitors have emerged as a potential alternative, but data on the selective JAK1 inhibitor upadacitinib in SAPHO syndrome are lacking. Case summary: An 18-year-old male presented with a 7-year history of recurrent facial acne since 2016. Whole-body bone scintigraphy revealed focally increased radiotracer uptake in the right clavicle, consistent with SAPHO syndrome. Initial treatment of acne with adapalene gel combined with oral minocycline failed to improve skin symptoms, leading to the decision to ultimately pursue biologic therapy. After four months of adalimumab therapy, the patient initially showed improvement in chest pain and dermatitis but subsequently experienced paradoxical worsening of facial acne accompanied by erythema and pruritus. No improvement was observed after an additional four weeks of continued adalimumab treatment. Following a transition to upadacitinib, facial lesions improved within 4 weeks and achieved marked resolution by 8 weeks. Conclusion: This report of upadacitinib in SAPHO syndrome demonstrates its rapid and substantial efficacy in a patient refractory to adalimumab. Upadacitinib may represent a promising treatment option for difficult-to-treat SAPHO syndrome, particularly in cases with inadequate response to TNF-α inhibition.

SAPHO syndrome is a rare autoinflammatory disorder with osteoarticular and cutaneous involvement. Paradoxical skin lesions have been reported during treatment with tumor necrosis factor-α (TNF-α) inhibitors. We describe a 42-year-old man with a 6-year history of SAPHO syndrome presenting with chronic sternoclavicular and lumbosacral pain and sterile pustules on the lower extremities. Conventional therapy with etoricoxib and methotrexate improved musculoskeletal symptoms but failed to resolve skin lesions, while adalimumab treatment led to progressive worsening of cutaneous manifestations. Following a switch to upadacitinib (15 mg once daily), rapid improvement of skin lesions and sustained control of musculoskeletal symptoms were achieved without adverse events. This case suggests that Janus kinase inhibition may represent a therapeutic option for TNF-α inhibitor–induced paradoxical skin lesions in SAPHO syndrome.

Fine particulate matter with a diameter ≤2.5 μm (PM_2.5) pollution poses a global public health crisis, demonstrating significant threats to human health. This study focused on the strategically important Chengdu-Chongqing Economic Circle in western China, systematically comparing the toxic effects of urban and rural PM_2.5 across five levels. PMF and regression analysis were used to identify source contributions, dual-omics to pinpoint key molecules, and epidemiological data with a GAM model to assess health risks. Findings demonstrate that rural PM_2.5 possesses greater biotoxicity than its urban counterpart. Cytotoxicity in urban and rural PM_2.5 originated from road dust/vehicle emissions and biomass burning, respectively. Subsequently, integrated omics and molecular biology analyses identify kinesin family member 20A (KIF20A) as a shared key target, which mediates toxicity induced by both urban and rural PM_2.5. Finally, epidemiological analysis reveals that females and ≥65 years old exhibit relatively high sensitivity to urban PM_2.5 exposure trends, with rhinitis showing a comparatively higher impact among various related diseases. The novelty of this work lies in its pioneering application of a multi-tiered investigative approach. This approach spans “environmental samples-cellular mechanisms-population health” within the Chengdu-Chongqing economic circle context, systematically elucidating common and distinct respiratory health risk of urban and rural PM_2.5. This work offers a vital scientific foundation for advancing region-specific, precise air pollution prevention and control measures.

Background: SAPHO syndrome is a rare chronic rheumatic disease characterized by five typical manifestations: synovitis, acne, pustulosis, hyperostosis, and osteitis. The follicular occlusion triad (FOT) comprises hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS). The associations of FOT with peripheral/axial spondyloarthritis remain poorly understood. This study aimed to delineate the pattern of possible peripheral/axial spondyloarthritis involvement in patients with FOT. Methods: All cases of FOT with peripheral/axial spondyloarthritis treated at our center were reported and compared with previously reported cases from the literature. Epidemiological and clinical data were collected from these cases. Results: Three cases of FOT with peripheral/axial spondyloarthritis from our center and 10 cases from the literature review were included. We confirmed the FOT diagnosis in these patients and analyzed their associated spondyloarthritis involvement. The clinical features and treatments of these cases were also summarized. Most patients were male (92.31%, 12/13). In all patients, skin lesions preceded the onset of spinal arthritis, with intervals ranging from 0.6 to over 15 years. Symptoms related to axial arthritis typically presented as cervical and/or lumbar pain and stiffness (46.15%, 6/13). Only a few patients exhibited the typical sternoclavicular involvement seen in SAPHO syndrome (15.38%, 2/13). Laboratory examinations revealed elevated inflammatory markers and negative rheumatoid factor/HLA-B27 in all patients. Prednisone and adalimumab were reported to provide prolonged remission, while one patient responded satisfactorily to isotretinoin treatment. Conclusion: We provide an updated overview of the disease pattern of peripheral/axial spondyloarthritis involvement in patients with FOT.