Objective To explore the effects of estradiol (E2) on the expression of epithelial cell inflammatory cytokines (IL-17/IL-36 family), as well as on JAK/STAT phosphorylation and phenotypic differentiation of T cells. Methods C.albicans infection models were established using VK2/E6E7 cells and human CD4+ naïve T lymphocytes, respectively. Both models were divided into four groups: a control group, an E2 group (containing 10-8 mol/L E2), a C.albicans group (containing 1×106 cfu/mL C.albicans), and a C.albicans+E2 group (containing 10-8 mol/L E2 and 1×106 cfu/mL C.albicans). In the VK2/E6E7 cell model, the expression levels of mRNA for inflammatory cytokines, including IL-17A, IL-17F, IL-36α, IL-36β, and IL-36γ, were detected by RT-qPCR, while protein levels were measured by ELISA. In the CD4+ naïve T lymphocyte model, the phosphorylation levels of JAK(1-3) and STAT(1-3) were detected by Western blot, and the expression levels of T cell phenotypic markers, such as CD45RO, CD69, and CD103, were analyzed by flow cytometry. Results In C.albicans-infected VK2/E6E7 cells, the expression levels of pro-inflammatory cytokines (IL-17A, IL-17F, IL-36α, IL-36β, and IL-36γ) were significantly upregulated compared to the control group (P<0.01). In contrast,the E2+C.albicans group significantly downregulated expression of these cytokines compared to the C.albicans group (P<0.01). In human CD4+ naïve T cells, phosphorylation levels of JAK(1-2) and STAT(1-2) were significantly increased in the C.albicans group compared to the control group (P<0.05), and were significantly decreased in the E2+C.albicans group compared to the C.albicans group (P<0.05), while no significant changes were observed for JAK3 and STAT3 (P>0.05). Additionally, the E2 group showed significant downregulation of CD45RO and CD69 expression (P<0.001) and significant upregulation of CD103 expression (P<0.001) compared to the control group. Conclusions E2 downregulates the expression levels of pro-inflammatory cytokines (IL-17A, IL-17F, IL-36α, IL-36β, IL-36γ) in C.albicans-infected vaginal epithelial cells and inhibits C.albicans-induced phosphorylation of JAK (1-2), STAT (1-2) in human CD4+ naïve T lymphocytes. By inhibiting the JAK/STAT signaling pathway, E2 reshapes the activation and tissue-residency phenotypes of CD4+ T cells, thereby impairing local antifungal immune clearance and promoting the pathogenesis of recurrent vulvovaginal candidiasis.
Objective This study aimed to construct a prodrug (PPA-SS-AA) by linking pyropheophorbide-a (PPA) with arachidonic acid (AA) via a disulfide bond and to prepare self-assembled nanoparticles using this prodrug. The goal was to address the poor water solubility and insufficient targeting of PPA and to further evaluate the efficacy and mechanisms of this nanosystem for photodynamic therapy (PDT) against melanoma in vitro. Methods The PPA-SS-AA prodrug was synthesized via EDCI/DMAP-catalyzed esterification and co-assembled with DSPE-PEG2000 into nanoparticles using the nanoprecipitation method. The particle size, polydispersity index (PDI), and Zeta potential of the nanoparticles were characterized using a nanoparticle size analyzer. The dark toxicity and phototoxicity of the nanoparticles were assessed by the CCK-8 assay in mouse melanoma B16 cells. Cellular uptake of the nanoparticles was investigated using flow cytometry and confocal microscopy. Apoptosis, cell death, and intracellular reactive oxygen species (ROS) generation were evaluated using Annexin V-FITC/PI double-staining flow cytometry, Calcein-AM/PI live-dead cell staining, and the DCFH-DA ROS probe, respectively. Results PA-SS-AA was successfully synthesized, and monodisperse nanoparticles with a particle size of 132.73 nm, a PDI of 0.102, and a Zeta potential of -23.24 mV were prepared. In vitro experiments showed that these nanoparticles could be efficiently taken up by B16 cells and exhibited a potent photodynamic killing effect under 633 nm laser irradiation, with an IC50 value of 14.43 μg/mL. Compared to the non-irradiated group, the cell viability in the irradiated group decreased to 12.3% (P<0.001), with an apoptosis rate of 51.95%, which was 5.89 times higher than that in the non-irradiated group (P<0.001). Mechanistic studies confirmed that the nanoparticles generated a large amount of ROS in the cells after irradiation, with levels 3.2 times higher than those in the non-irradiated group (P<0.001), effectively triggering the apoptotic pathway. Conclusions This study successfully constructs a self-assembled nano-delivery system based on PPA-SS-AA. This system significantly improves the delivery efficiency of PPA and efficiently generates ROS upon photoactivation, thereby inducing apoptosis and cell death in melanoma cells, demonstrating excellent potential for in vitro photodynamic therapy. This prodrug-based nanoplatform presents a promising new strategy for the precise treatment of melanoma.
Objective To evaluate the clinical efficacy of self-formulated traditional Chinese medicine compound decoction combined with fire needle bloodletting in treating cystic acne. Methods Eighty patients with cystic acne admitted to our hospital from January 2023 to March 2025 were enrolled and randomly divided into a control group (n=40) and an observation group (n=40). The control group was treated with oral isotretinoin capsules combined with fire needle bloodletting therapy, while the observation group received the self-formulated traditional Chinese medicine compound decoction combined with fire needle bloodletting therapy. The total clinical effective rates, skin lesion scores, Dermatology life quality index scores, serum inflammatory factor levels (TNF-α, CRP, IL-6, IL-1β), and facial sebum content were compared between the two groups before and after 7, 14, and 28 days of treatment. A generalized estimating equation model was used to analyze the time and group effects on skin lesion scores and DLQI scores. The incidence of adverse reactions during the treatment was compared between the two groups. Results The total clinical effective rate was significantly higher in the observation group than in the control group (95.00% vs. 75.00%, χ2=5.17,P=0.023). At all post-treatment time points, skin lesion scores, inflammatory factor levels, and sebum content significantly decreased (P<0.05), while DLQI scores significantly increased (P<0.05) compared with baseline in both groups. The observation group demonstrated greater improvement than the control group on all indices (P<0.05). The Generalized Estimating Equation analysis revealed significant interaction effects between time and group on both skin lesion scores and DLQI scores (P<0.001). The total incidence of adverse reactions in the observation group was significantly lower than that in the control group (7.50% vs. 25.00%, χ2=4.50,P=0.034). Conclusions The combination of traditional Chinese medicine compound decoction and fire needle bloodletting is effective in reducing skin lesions, improving quality of life, lowering inflammatory levels, and decreasing sebum secretion in patients with cystic acne. Furthermore, it demonstrates a better safety profile compared to the combination of oral isotretinoin and fire needle bloodletting, suggesting its potential for clinical application.
Objective The aim of this study was to investigate the expression levels of CXCL4 in the peripheral blood of patients with alopecia areata and to provide evidence for the pathogenesis of alopecia areata and the development of new therapeutic targets. Methods Sixty patients with alopecia areata (alopecia group) and 30 healthy controls (control group) were enrolled. The expression levels of CXCL4 mRNA in the peripheral blood mononuclear cells (PBMCs) were detected by qRT-PCR, and the content of CXCL4 in the serum was detected by ELISA. The relationship between CXCL4 expression and age, gender, disease duration, disease activity, and severity (SALT score) was analyzed. Results The expression levels of CXCL4 mRNA in PBMCs of the alopecia group were significantly higher than those of the control group (Z=-3.65, P<0.001). The expression levels of CXCL4 mRNA in patients with different severity, clinical stages, and disease durations were all higher than those of the control group (all P<0.05), but there was no significant difference among the subgroups of alopecia areata (all P>0.05). The content of CXCL4 in the serum of the alopecia group was significantly higher than that of the control group (Z=-3.90, P<0.001); the serum CXCL4 levels in each subgroup were also higher than those of the control group (all P<0.05), with no significant difference among the subgroups of alopecia areata (all P>0.05). There was no significant correlation between serum CXCL4 protein levels or CXCL4 mRNA levels and the SALT score (P>0.05). Conclusions The expression levels of CXCL4 in the peripheral blood of alopecia patients are increased, suggesting that it may be involved in the pathological process of alopecia. Although it does not significantly correlate with the severity of the disease, it can still be used as a potential auxiliary diagnostic marker and provide a reference for early screening.
Objective To explore the clinical efficacy of autologous chylous fat transplantation in improving facial wrinkles, skin laxity, and enlarged pores in subjects with moderate to severe facial photoaging, as well as to ascertain its clinical applicability and safety. Methods A total of 20 subjects with moderate to severe facial photoaging admitted to our hospital from June 2023 to July 2024 were enrolled, all of whom underwent autologous chylous fat transplantation. Fat was harvested from their thighs or abdomen, purified, and emulsified into chylous fat, which was then precisely injected into the areas with facial wrinkles and enlarged pores. Before surgery and three months after surgery, Glogau’s four-grade photoaging classification was used to evaluate the grade of facial wrinkles. An ElastiMeter skin firmness tester was employed to measure skin firmness, while a five-point photographic scale was used to quantitatively assess pore improvement. The occurrence of postoperative complications was recorded. Results At 3 months after surgery, the average grade of facial wrinkles decreased from 3.52±0.80 preoperatively to 2.03±0.30 (t=0.43, P=0.011). Skin firmness increased from 20.34±3.80 to 29.51±5.50 (t=0.32, P=0.001), and the average grade of pores reduced from 3.70±1.21 to 2.10±1.01 (t=0.65, P=0.012). Postoperatively, there were 1 case of edema and 1 case of fat necrosis, with no serious adverse events observed. Conclusions Autologous chylous fat transplantation can significantly improve wrinkles, skin laxity, and enlarged pores caused by facial photoaging. The incidence of postoperative complications was low, indicating that this treatment is safe and effective for the treatment of facial photoaging.
Objective To establish a prediction model for systemic sclerosis (SSc)-related interstitial lung disease (ILD) using LASSO-regularized logistic regression. Methods Patients diagnosed with systemic sclerosis at the First Affiliated Hospital of Zhengzhou University from January 2019 to June 2024 were included as study subjects. They were divided into a case group (99 cases, SSc-ILD group) and a control group (62 cases, SSc-non-ILD group) based on the presence or absence of interstitial lung disease. Univariate analysis and LASSO regression were first used for variable screening, with the selected variables serving as independent variables in multivariate logistic regression. Based on the final independently identified risk factors, a predictive model was established using R software, and its discrimination ability, calibration level, and clinical efficacy were evaluated. Results A prediction model established based on LASSO-logistic regression included five predictors: the dcSSc subtype, cough, digital ulcers, positivity for anti-Scl-70 antibodies, and lower serum albumin levels. Based on these factors, a diagnostic prediction model was established. The ROC curve demonstrated an AUC of 0.815 (95%CI: 0.748~0.882), indicating good discriminative ability. The calibration curve closely approximated the reference line, showing excellent calibration performance. The DCA results revealed that this clinical prediction model exhibited high net benefit across a broad range of thresholds, demonstrating strong clinical utility. Conclusion The prediction model developed in this study to predict interstitial lung disease (ILD) in patients with SSc demonstrates good clinical applicability.
Dermatology is a clinical discipline that heavily relies on morphology, with its clinical manifestations, closely related to pathological changes and immune mechanisms. The traditional disease name-based teaching model lacks a connection between clinical, pathological, and immunological knowledge, making it difficult for students to establish a systematic knowledge framework. This article explores an integrated teaching model of clinicopathological-immunological correlation (CPIC). The model comprises three modules: description of skin lesions, Ackerman diagnostic pathways, and the basics of dermatological immunology, led by real cases, following a teaching process of connection of “clinical observation, histopathological pattern diagnosis, immunological mechanism analysis, and differential diagnosis”.Teaching practice demonstrates that this approach helps students establish a systematic clinical reasoning framework and improves their histopathological interpretation and clinical analysis skills.
We report a case of Dowling-Degos disease. A 47-year-old female presented with a 10-year history of black-brown macules and papules on the neck, inframammary region, axillae, groin, and external genitalia. Dermatological examination revealed symmetrical brown to black-brown macules, papules, and flat papules in the skinfold areas, such as the neck, under the breasts, armpits, abdomen, groin, and external genitalia, with some areas showing a confluent, reticular pattern. Histopathological examination of the skin lesions showed slight acanthosis with markedly elongated, finger-like epidermal rate ridges, hyperpigmentation of the basal layer, moderate lymphocytic infiltration in the superficial dermis, and melanophages. Diagnosis: Dowling-Degos disease. The patient declined treatment.
We report a case of facial lichen planus pigmentosus. A 54-year-old female complained of brown spots on her face for two months. Two months ago, the patient developed a large pale erythema on her forehead and cheeks of unknown cause, characterized by unclear boundaries and mild itching. The pale erythema gradually transformed into large dark brown spots. A dermatological examination revealed diffuse patchy brown spots on the forehead and cheeks, some of which had a reticular appearance and unclear boundaries. Confocal laser scanning microscopy showed focal thickening of the granular layer, irregular thickening of the spinous layer, liquefaction degeneration of the basal layer, and infiltration of phagocytic and inflammatory cells in the superficial and papillary layers of the dermis. Pathological results indicated hyperkeratosis, wedge-shaped thickening of the granular layer, thickening and edema of the spinous layer, a few colloid bodies beneath the epidermis, liquefaction degeneration of the basal layer, and inflammatory infiltration of lymphocytes, phagocytes, and a few histiocytes in the dermal papillary layer. The diagnosis was facial lichen planus pigmentosus. The patient was treated with 75 mg of oral cyclosporine soft capsules twice daily, an intramuscular injection of 1 mL of compound betamethasone once, and topical 0.03% tacrolimus ointment to be applied at bedtime for one month. The patient has lost to follow-up.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by persistent inflammation, intractable pruritus, and skin barrier impairment, in which dysregulation of the neuro-immune-barrier network represents a key pathogenic mechanism. As major regulators of the neuroimmune axis, neurotransmitters can be functionally classified into excitatory, inhibitory, and auxiliary modulatory groups, and their imbalance directly contributes to inflammatory amplification, itch persistence, and barrier dysfunction in AD. Excitatory neurotransmitters, including norepinephrine/epinephrine, glutamate, and acetylcholine, mainly mediate inflammatory activation and pruritic signal transmission through receptors such as β2-adrenergic receptor (β2AR), glutamate receptor kainate 2 (GluK2), and nicotinic acetylcholine receptor (nAChR). Inhibitory neurotransmitters, such as γ-aminobutyric acid and glycine, regulate neural sensitization and maintain itch homeostasis through inhibitory circuits in the spinal dorsal horn. Auxiliary modulatory neurotransmitters, including tryptophan, 5-hydroxytryptamine, and melatonin, are involved in barrier repair and inflammatory integration via metabolic pathways, circadian regulation, and microbiota-related interactions. Translational evidence indicates that the AhR axis is now entering the stage of clinical therapeutic exploration, while GABA receptors, GluK2, HTR7, and topical melatonin delivery remain largely at the preclinical stage. This review summarizes the core mechanisms and translational implications of functionally distinct neurotransmitter groups in AD, providing a theoretical basis for the development of novel diagnostic and therapeutic strategies targeting the neuroimmune axis.
The pathogenesis of chronic actinic dermatitis (CAD) is closely associated with immune imbalance in CD4+ T-cell subsets, particularly the dysregulation of the T-helper (Th)1/Th2 and Th17/regulatory T cell (Treg) axes. In CAD patients, Th1 cells are abnormally activated and secrete pro-inflammatory cytokines such as IFN-γ and IL-1β, which exacerbate inflammatory responses. Th2 cells release IL-4, IL-5, IL-13, and CCL18, promoting eosinophil infiltration and elevating IgE levels, thereby aggravating skin lesions. Meanwhile, the Th17/Treg imbalance is characterized by an increased proportion of Th17 cells and a decrease in Treg cell number or function, alongside aberrant expression of the key transcription factor FOXP3, further driving immune-mediated inflammation. These T-cell subsets interact through complex regulatory networks and collectively contribute to the development and progression of CAD. Therefore, targeting the expression of relevant cytokines and restoring the balance between Th1/Th2 and Th17/Treg may represent a promising therapeutic strategy for CAD. This review summarizes current research on the role of Th1/Th2 and Th17/Treg immune imbalance in the pathogenesis of CAD, aiming to provide new insights into its mechanisms and clinical management.
Hair regeneration has become a key therapeutic strategy for alopecia and related disorders. Rapid advances in stem cell biology and tissue engineering have revealed substantial clinical potential. The formation and regeneration of hair follicles depend on complex cellular and molecular mechanisms, where stem cells play a pivotal role in follicular development and functional recovery through self-renewal and multipotency. Researchers have employed tissue engineering techniques, such as designing biomimetic three-dimensional microenvironments and nanomaterial-based scaffolds, to generate functional hair follicles in vitro, facilitating clinical translation. However, clinical implementation faces persistent challenges, including the standardization of stem cell sources, management of immune rejection risks, addressing the structural complexity of hair follicles, and obtaining sufficient long-term safety data. This review systematically outlines recent progress in the fundamental mechanisms and clinical translation of hair regeneration. It provides a comprehensive reference for researchers and clinicians to guide future studies and applications.