Hongzhong Jin

As the largest and most externally exposed organ, the skin is particularly vulnerable to aging, rendering skin aging a widespread clinical and aesthetic concern. Driven by both intrinsic and extrinsic factors, skin aging is characterized by progressive functional decline and structural remodeling that compromise barrier integrity, disrupt dermal homeostasis, and ultimately diminish quality of life. At the upstream regulatory level, skin aging-associated epigenetic modifications drive epigenetic drift that compromises transcriptional fidelity and primes cells toward senescence. At the cellular level, regulatory mechanisms converge on cellular senescence and profound mitochondrial remodeling. At the microenvironmental level, the failure of senescent cell clearance (immunosenescence) and the emergence of a chronic pro-inflammatory milieu (inflammaging) create a self-reinforcing immune-inflammatory axis. This axis exacerbates cytokine production, extracellular matrix remodeling, and progressive tissue degeneration. We further highlight emerging mechanism-targeted interventions, including epigenetic and mitochondrial modulators, senotherapeutics, biologics, immunotherapies, regenerative and device-based therapies. A deeper understanding of these interconnected molecular mechanisms and targeted therapies may offer a roadmap for future therapeutic innovation and translational research in skin aging.

Purpose: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder. Although mucosal involvement is uncommon, it may indicate a more severe clinical phenotype. This study evaluated the prevalence and clinical features associated with mucosal involvement in BP. Patients and Methods: This retrospective cohort study included 265 patients with BP diagnosed at Peking Union Medical College Hospital between January 2013 and May 2022. Clinical, laboratory, immunological, and treatment-related characteristics were compared between patients with and without mucosal involvement. Logistic regression analyses were performed to identify factors associated with mucosal involvement, and model performance was assessed using receiver operating characteristic analysis. Results: Seventy-one patients (26.8%) had mucosal involvement, most commonly affecting the oral mucosa, followed by genital and ocular sites. Compared with patients without mucosal lesions, those with mucosal involvement were younger at disease onset, more frequently had a history of malignancy, and showed a more severe clinical phenotype, including higher hospitalization rates, more infections within 1 year, higher corticosteroid requirements, higher BPDAI scores, and more frequent head/neck and hands/feet involvement. Indirect immunofluorescence seropositivity and peripheral eosinophilia were less frequent in patients with mucosal involvement. In multivariate analysis, head/neck involvement (adjusted OR 8.276, 95% CI 2.211– 30.977), hands/feet involvement (adjusted OR 34.559, 95% CI 8.191– 145.805), and higher BPDAI score (adjusted OR 1.055, 95% CI 1.020– 1.091) were independently associated with mucosal involvement, whereas peripheral eosinophilia was inversely associated (adjusted OR 0.027, 95% CI 0.005– 0.148). The model demonstrated excellent apparent discrimination (AUC 0.937). Conclusion: Mucosal involvement in BP is associated with a more severe clinical phenotype. Head/neck and acral involvement, higher BPDAI scores, and a lower frequency of peripheral eosinophilia may serve as practical clinical indicators for identifying patients who require closer mucosal assessment and more intensive monitoring. Plain Language Summary: Bullous pemphigoid is a skin disease that mainly affects older adults and causes large blisters on the skin. In some patients, the disease also affects the mouth or other mucosal surfaces. Doctors consider this type of involvement uncommon, and they still know little about which patients are more likely to develop it. In this study, we analyzed medical records from 265 patients with bullous pemphigoid treated at a large hospital in China. We compared patients who had mucosal involvement with those who did not. We aimed to identify clinical features that may help doctors recognize patients who need closer mucosal assessment and monitoring. We found that about one in four patients had mucosal involvement. These patients tended to develop the disease at a younger age and often had more severe skin disease. They were also more likely to require hospitalization and stronger treatment. Skin lesions on the head, neck, hands, and feet were more common in these patients. In addition, these patients less often had increased eosinophils, a type of white blood cell, in their blood. Our results suggest that mucosal involvement may represent a more severe form of bullous pemphigoid. Recognizing these clinical features may help doctors identify these patients earlier and provide closer monitoring and more appropriate treatment.

Introduction Prurigo nodularis (PN) is a chronic inflammatory dermatosis with severe, persistent pruritus and limited effective therapies. Janus kinase (JAK) inhibition has emerged as a targeted strategy for PN. Methods This phase I/II, randomized, double-blind, vehicle-controlled, multicenter clinical trial was conducted in China to evaluate the safety, pharmacokinetics, and efficacy of topical 1.5% ruxolitinib gel (HDM3010) in adults with PN. Adult patients with PN were randomized 2:1 to receive HDM3010 or vehicle, administered once daily (QD) or twice daily (BID), during a 4-week double-blind treatment period. Results Forty-nine patients were randomized. HDM3010 demonstrated a safety profile characterized by treatment-emergent adverse events in 18.8% of QD and 25.0% of BID patients, compared with 12.5% of vehicle QD and 55.6% of vehicle BID patients. Treatment-related adverse events were infrequent (4.1%) and limited to mild-to-moderate severity. Pharmacokinetic analyses showed low systemic exposure, with mean peak plasma concentrations below 7 ng/mL at steady state. Compared with vehicle, HDM3010 was associated with higher proportions of ≥ 4-point Worst Itch Numerical Rating Scale (WI-NRS) responders and greater improvements in WI-NRS, Investigator’s Global Assessment for Prurigo Nodularis–Stage (IGA PN-S), and Investigator’s Global Assessment for Prurigo Nodularis-Activity (IGA PN-A) scores. Conclusions HDM3010 demonstrated a favorable safety profile, minimal systemic exposure, and positive trends in reducing pruritus and lesions in adults with PN. Trial Registration Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR2500096434 (registered January 23, 2025).

Psoriasis is associated with elevated cardiovascular risk, partly mediated through dyslipidemia and the interleukin-23/Th17 inflammatory axis. Interleukin-17A (IL-17A) inhibitors demonstrate superior dermatologic efficacy, but their effects on lipid metabolism remain controversial. Most previous studies analyzed lipid changes at the population level without stratifying by baseline lipid phenotypes. This study aimed to evaluate the phenotype-specific effects of IL-17A inhibitors on lipid profiles and identify risk factors for dyslipidemia in moderate-to-severe plaque psoriasis. This retrospective cohort study included 353 patients with moderate-to-severe plaque psoriasis (body surface area [BSA] ≥ 3%) treated with IL-17A inhibitors (secukinumab or ixekizumab) for one year. Patients were stratified into five mutually exclusive lipid phenotypes according to the 2023 Chinese guidelines for lipid management. Multivariable logistic regression identified independent risk factors for dyslipidemia. Lipid changes were assessed using paired tests with Benjamini-Hochberg false discovery rate (FDR) correction. Sensitivity analyses were performed in the BSA ≥ 10% subgroup (n = 274). Dyslipidemia was present in 72.2% of patients, with mixed dyslipidemia (26.1%) and hypertriglyceridemia (21.2%) being predominant. BMI ≥ 28 kg/m² (OR = 3.35, 95% CI 1.79-6.28, P < 0.001) and male sex (OR = 2.37, 95% CI 1.40-4.01, P = 0.001) were independent risk factors. Phenotype-specific effects were observed: mixed dyslipidemia patients showed significant reductions in TC (0.47 mmol/L), TG (0.46 mmol/L), and LDL-C (0.18 mmol/L) (all FDR-adjusted P ≤ 0.010); hypercholesterolemia patients demonstrated reductions in TC (0.49 mmol/L) and LDL-C (0.43 mmol/L) (both FDR-adjusted P < 0.001). Among 110 patients with baseline LDL-C ≥ 3.4 mmol/L, 31.0% achieved LDL-C < 3.4 mmol/L. Hypertriglyceridemia patients showed no significant changes after FDR adjustment. Isolated low HDL-C patients exhibited modest increases in HDL-C and LDL-C. Normal lipid patients experienced mild increases in TG and LDL-C within normal ranges. Psoriasis Area and Severity Index (PASI) improvement showed no correlation with lipid changes (all FDR-adjusted P > 0.05). Sensitivity analyses confirmed the robustness of all primary findings. IL-17A inhibitors exert heterogeneous, phenotype-dependent effects on lipid metabolism. Patients with elevated baseline cholesterol may derive dual dermatologic and cardiometabolic benefits, while those with normal lipids require monitoring for modest unfavorable changes. These findings support phenotype-guided treatment selection and individualized lipid monitoring strategies.

While bullous pemphigoid (BP) can be induced by various drugs, cases involving small-molecule inhibitors remain rare. We report the first case of BP occurring in a patient with psoriasis shortly after receiving deucravacitinib, a TYK2 inhibitor. Following treatment with methylprednisolone, minocycline, and ixekizumab, the lesions resolved within one month. Although the precise mechanism remains unclear, it may involve immunological drift and remodeling of skin immune microenvironment, which raises the need for clinical awareness regarding such reactions when using novel targeted immunomodulators.

Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disorder. Laboratory parameters may serve as an assessment tool, providing a potential objective window into disease activity. To systematically evaluate the utility of commonly obtained laboratory parameters in the objective assessment of disease severity in patients with HS. This single-center retrospective study included patients who were clinically diagnosed with HS, acne inversa, or follicular occlusion triad at Peking Union Medical College Hospital between January 1, 2020, and July 1, 2025. Study data were extracted from clinical examination records and corresponding laboratory test results. Ordinal logistic regression models were constructed to evaluate the associations between laboratory parameters and Hurley stages. Heterogeneity analyses were performed to assess the consistency of these associations across anatomical regions. The study included 1750 clinical visits from 583 HS patients, with a male predominance (85.7%) and a mean age of 31.15±12.11 years. By systematically comparing laboratory parameters across Hurley stages, this study identified significant differences in ten markers, including white blood cell (WBC), neutrophil ratio (NEU%), platelet (PLT), plateletcrit (PCT), mean platelet volume (MPV), hemoglobin (Hb), gamma-glutamyl transferase (GGT), high-density lipoprotein cholesterol (HDL-C), erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (hsCRP). Ordinal logistic regression analyses demonstrated that WBC, NEU%, PLT, PCT, platelet distribution width (PDW), GGT, ESR, and hsCRP were significantly and positively associated with increasing Hurley stage, while Hb, MPV, and HDL-C exhibited inverse associations. Heterogeneity analysis found that systemic inflammation-related markers (WBC, PDW, ESR, and hsCRP) demonstrated highly consistent associations with HS severity across anatomical locations, while metabolic parameters (HDL-C, triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) exhibited significant site-specific heterogeneity. This study supports the use of readily available laboratory markers as an objective adjunct to conventional clinical severity assessments, while highlighting the anatomical specificity of HS pathophysiology.

Owing to impaired glucose metabolism, the high-glucose microenvironment in diabetic patients disrupts a series of biological reactions that hinder the wound healing process, resulting in a significant cost to the health care system and an urgent need for new and advanced therapies. In this study, induced pluripotent stem cell-derived exosomes (iPSC-Exos) were isolated from iPSC culture supernatant via centrifugation and ultrafiltration. We evaluated the therapeutic effects of iPSC-Exos on diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and streptozotocin (STZ)-induced diabetic mouse model). iPSC-Exos were topically administered to full-thickness cutaneous wounds in diabetic mice. The therapeutic effects were systematically assessed by measuring wound closure rates, conducting comprehensive histopathological evaluations, and performing quantitative analysis of inflammatory mediators via ELISA. We demonstrated that iPSC-Exos can significantly accelerate diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and STZ-induced diabetic mouse model) for the first time. The multifaceted therapeutic mechanisms include: (ⅰ) Direct activation of tissue regeneration (promotion of re-epithelialization, tissue remodeling and scar attenuation); (ⅱ) Modulation of the inflammatory microenvironment (promoting macrophage polarization toward anti-inflammatory M2 phenotype/suppressing inflammation). This dual-animal model approach, which closely recapitulates key pathophysiological features of human diabetic wounds, offers superior clinical translatability compared to single-animal model studies. Our findings not only establish a robust scientific foundation for clinical development of iPSC-Exos therapy, but also present a transformative, cell-free treatment paradigm for chronic diabetic wounds that addresses critical unmet medical needs.