Allergen specific immunotherapy（AIT）, as an effective treatment for allergic rhinitis, asthma, and other allergic diseases, has received widespread attention in the field of health economic evaluation in recent years. This article reviews the current status and progress of economic research on AIT, mainly discussing the socioeconomic burden of allergic rhinitis, the results of health economic studies from different countries, and the primary methods used in health economic research on allergic rhinitis. Existing studies indicate that, although AIT involves high initial costs, it offers significant long-term economic benefits by reducing healthcare resource utilization, improving patient quality of life, and decreasing medication dependence. Moreover, reducing initial costs, applying standardized assessment tools, and conducting cross-national comparative analyses have become key directions for future research. Overall, AIT demonstrates strong potential in terms of long-term health benefits and cost savings, providing solid economic evidence for the management of allergic diseases.
Humans ; Desensitization, Immunologic/economics* ; Cost-Benefit Analysis ; Rhinitis, Allergic/economics* ; Economics, Medical

Extracellular vesicles (EVs) are crucial for facilitating intercellular communication, promoting cell migration, and orchestrating the immune response. Recently, EVs can diagnose and treat tumors. EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy. Furthermore, EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs. Herein, we review the molecular composition, biogenesis, and separation methods of EVs. We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy. Finally, we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Objective:To observe the in vivo microscopic histological changes during the treatment of melasma using reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT), and to explore its application value in evaluating therapeutic efficacy. Methods:Clinical data were collected from 30 melasma patients treated at the Department of Dermatology, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, from January to October 2023. Retrospective analyses were performed on clinical photographs taken before treatment and at weeks 4, 8, 12, and 16 after the start of treatment, and the efficacy was evaluated by using the melasma area and severity index (MASI) scores. Meanwhile, changes in RCM imaging indicators, such as pigment distribution patterns, melanocyte morphology and spatial distribution patterns, and inflammatory infiltration in the superficial dermis in melasma lesions, were retrospectively analyzed. For clear elucidation of concepts and subsequent quantitative analysis, characteristic microscopic histological changes in melasma lesions before treatment were classified into several patterns based on RCM findings and previous literature reports. Additionally, optical coherence signals collected by OCT were used to asses characteristic vessel parameters in the lesions before and after treatment. Finally, correlations between various microscopic histological changes and clinical efficacy were analyzed using Spearman's correlation analysis.Results:With the increase in treatment duration, the proportions of pigment distribution patterns Ⅱ and Ⅲ observed by RCM gradually decreased, while the proportion of the nearly normal pattern Ⅰ markedly increased; the proportions of the 4 heterogeneous morphological patterns of melanocytes all decreased, while the pattern Ⅱ melanocytes were still focally distributed in the lesions at the last time of observation; meanwhile, the proportions of melanocyte spatial distribution patterns Ⅱ and Ⅲ decreased, which gradually restored to the normal pattern Ⅰ; the infiltration of melanophages and inflammatory cells in the superficial dermis diminished, and the proportion of the pattern Ⅲ inflammatory infiltration markedly decreased at week 4, but it lasted for a long time. The decrease rate of MASI scores was significantly correlated with the decrease rate of the proportions of pigment distribution patterns Ⅱ and Ⅲ ( r = 0.82, 0.97, respectively, both P < 0.05), melanocyte morphological patterns Ⅰ, Ⅲ, and Ⅳ ( r = 0.84, 0.83, 0.83, respectively, all P < 0.05), and inflammatory infiltration patterns Ⅰ and Ⅲ ( r = 0.85, 0.81, respectively, both P < 0.05), as well as the increase rate of the proportion of melanocyte spatial distribution pattern Ⅰ ( r = 0.89, P < 0.05), indicating that these indicators can be sensitive evaluation indicators for clinical efficacy. Moreover, OCT revealed a decrease in the average diameter and density of vessels in the lesions after treatment, and the decrease rates were correlated with the decrease rate of MASI scores ( r = 0.76, 0.78, respectively, both P < 0.05) ; there was no significant difference between the pre- and post-treatment average depth of vascular plexuses. Conclusion:During the treatment of melasma, RCM combined with OCT could serve as a non-invasive approach with objective and robust evidence for evaluating the therapeutic efficacy.

Objective:To analyze the dermoscopic and reflectance confocal microscopic (RCM) features of extragenital lichen sclerosus, and to identify their associations with histopathological manifestations.Methods:A total of 57 patients with histopathologically confirmed lichen sclerosus were retrospectively collected from the Department of Dermatology, Wuhan No.1 Hospital from October 2010 to April 2024. Dermoscopic and RCM images were collected from typical skin lesions in extragenital areas, and the consistency between dermoscopic or RCM characteristics and histopathological features was analyzed.Results:Among the 57 patients with extragenital lichen sclerosus, there were 15 males and 42 females, with ages ranging from 5 to 60 years and disease duration from 5 to 28 months. The skin lesions were mainly located on the face and neck (23 cases, 40.4%) and back (11 cases, 19.3%). Histopathological features included hyperkeratosis with follicular plugging, vacuolar degeneration of basal cells, edematous papillary and superficial dermis, collagen homogenization, and predominant infiltration of variable amounts of melanophages and lymphocytes in the superficial dermis. Dermoscopy showed yellowish-white structureless areas in 57 cases (100%), yellowish-white circular structures in 55 (corresponding to follicular keratotic plugs, 96.5%), characteristic vascular structures in 54 (94.7%), gray-brown punctate pigmentation in 56 (98.3%), xanthochromic patchy pigmentation in 20 (35.1%), white scales in 54 (94.7%), white scar-like hypopigmentation in 43 (75.4%), and hemorrhagic spots in 2 (3.5%). RCM images showed follicular plugging in 44 cases (77.19%), manifesting as dilated follicular infundibula containing highly refractive keratotic materials; liquefaction degeneration of the basal cell ring was observed in 57 cases (100%), manifesting as loss of the basal cell ring, blurred epidermal-dermal junction, and infiltration of variable amounts of melanophages and inflammatory cells in the superficial dermis; dilatation of superficial dermal blood vessels was seen in 46 (80.7%) ; all 57 cases (100%) showed reduced epidermal thickness compared to surrounding normal skin, epidermal atrophy and thinning, and rete ridge flattening; hyperkeratosis was observed in 57 cases (100%) ; 39 cases (68.42%) showed thickened fibers with increased refractivity in the superficial dermis. The detection rates of follicular keratotic plugs, patchy pigmentation, and white scar-like hypopigmentation by dermoscopy significantly differed from those by histopathological examinations (all P < 0.05), so did the detection rates of superficial dermal collagen thickening and vascular dilatation by RCM (both P < 0.05) . Conclusions:Extragenital lichen sclerosus has characteristic dermoscopic and RCM manifestations, which were highly consistent with its histopathological findings. Dermoscopy combined with RCM technology can provide effective support for the diagnosis and differential diagnosis of extragenital lichen sclerosus.

Objective:To analyze micromorphological changes in psoriatic lesions before and after short-term treatment with secukinumab by dermoscopy and reflectance confocal microscopy (RCM), and to provide reliable microscopic indicators for monitoring the treatment efficacy.Methods:Nineteen patients with moderate to severe plaque psoriasis treated with secukinumab were collected from the Department of Dermatology, Wuhan No. 1 Hospital between July and December 2021. Dermoscopy and RCM were performed on same lesions in every patients at weeks 0, 2, and 4 after the start of treatment, and clinical evaluation was conducted at the same time. The changes in clinical scores, dermoscopic scores, and RCM characteristics before and after treatment were analyzed.Results:Dermoscopy showed that the bright red background of psoriatic lesions gradually lightened, pigmentation gradually increased, scales markedly decreased, and dotted/globular vessels changed from a uniform and regular distribution pattern to a clustered distribution pattern or completely disappeared after 2 to 4 weeks of treatment. As RCM revealed, after 2 and 4 weeks of treatment, the epidermal thickness decreased; the thicknesses from the stratum corneum to the dermal papilla at weeks 0, 2, and 4 were 76.85 ± 21.08 μm, 56.93 ± 16.58 μm, and 52.45 ± 15.76 μm, respectively; epidermal parakeratosis was alleviated or disappeared, inflammatory cells also decreased in number or disappeared in the epidermis and dermis, vascular dilatation was alleviated in the dermal papilla, and the structure of dermal papillary rings gradually became brighter in color after the treatment; the diameters of the dermal papillae decreased, measuring 53.96 ± 4.65 μm, 45.54 ± 5.11 μm, and 41.47 ± 4.54 μm at weeks 0, 2, and 4, respectively.Conclusion:The changes of microscopic indicators in psoriatic lesions are closely related to clinical efficacy, and the recovery of the dermal papillary ring structure by RCM can serve as an early observational indicator for the control of inflammation in psoriatic lesions and as an early predictive indicator for the effectiveness of subsequent treatment.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Objective·To explore the role of miR-128-3p/leptin(LEP)axis in the proliferation and inflammation of keratinocytes in psoriasis.Methods·BALB/c mice were randomly divided into a control group(n=10)and a model group(n=10).Mice in the model group were given imiquimod on the back.miR-128-3p overexpression and interference plasmids,as well as LEP interference plasmids,were constructed and transfected into HaCaT cells,respectively.miR-128-3p and LEP mRNA were quantified by real-time quantitative polymerase chain reaction,and LEP protein levels were detected by using Western blotting.Enzyme-linked immunosorbent assay was used to measure the content of tumor necrosis factor α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the culture medium.MTT assay was used to evaluate cell activity and EdU assay was to used to test cell proliferation.The binding site between miR-128-3p and LEP was determined by using a dual luciferase reporter gene assay.Results·Compared with mice in the control group,mice in the model group showed downregulated expression of miR-128-3p and upregulated expression of LEP at both RNA and protein levels(all P＜0.05).The dual luciferase reporter gene assay confirmed that LEP was a downstream target of miR-128-3p.Compared with the negative control mimic(NC mimic)group,expression of miR-128-3p was up-regulated in the miR-128-3p mimic group,and expression of LEP was reduced.The levles of TNF-α,IL-6,and IL-1β were significantly lower in the miR-128-3p mimic group than in the NC mimic group.The relative cell viability and EdU-positive cell rate were also reduced after miR-128-3p up-regulation(all P＜0.05).Compared with the negative control inhibitor(NC inhibitor)group,expression of miR-128-3p was down-regulated in the miR-128-3p inhibitor group,and expression of LEP was increased.The levles of TNF-α,IL-1β and IL-6 were increased after miR-128-3p downregulation.miR-128-3p down-regulation led to an increase in relative cell viability and EdU-positive cell rate(all P＜0.05).Further experimental results showed that LEP expression was up-regulated in the miR-128-3p inhibitor+LEP inhibitor group compared with that in the LEP inhibitor group,whereas the levels of TNF-α,IL-6,and IL-1β were elevated,and the relative viability of the cells and the rate of EdU-positive cells were increased(all P＜0.05).Conclusion·miR-128-3p downregulates LEP to inhibit the proliferation and inflammatory response of keratinocytes,thereby inhibiting the occurrence and development of psoriasis.

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharides （DOP） in reversing carbon tetrachloride （CCl₄）-induced hepatic fibrosis （HF） in rats via the Notch signaling pathway and evaluate the therapeutic effect of DOP by ultrasound elastography. MethodFifty-six male SD rats were randomized into normal， model， colchicine （1×10^-4 g·kg^-1）， Fuzheng Huayu powder （0.45 g·kg^-1）， and low-， medium-， and high-dose （0.05， 0.1， 0.2 g·kg^-1） DOP groups （n=8）. The rats in the model group and each treatment group were injected subcutaneously with a mixture of CCl₄-olive oil （2∶3） once every 3 days for 10 weeks. After 6 weeks of modelling， the rats were administrated with corresponding drugs once a day for 4 weeks. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe the pathomorphological changes of the liver tissue. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， and total bile acids （TBA）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of hyaluronic acid （HA）， laminin （LN）， type Ⅲ precollagen （PC-Ⅲ）， and type Ⅳ collagen （Col-Ⅳ）. The mRNA and protein levels of α-smooth muscle actin （α-SMA）， Notch1， Jagged1， and Hes1 in the liver tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The Young's modulus （YM） of the rat liver was measured by acoustic radiation force impulse （ARFI） elastography before and after treatment. Then， the correlations of YM with the serum levels of HA， LN， PC-Ⅲ， and Col-Ⅳ and the protein levels of α-SMA and Notch1 signaling pathway-related factors in the liver tissue were analyzed. ResultCompared with the normal group， the model group showed disordered arrangement of liver cell cords， obvious infiltration of inflammatory cells， appearance of a large number of fat vacuoles， and fibrous proliferation， elevated levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum， and up-regulated mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.01）. Compared with the model group， drug interventions alleviated the pseudolobule formation and the collagen deposition in confluent areas. Except that the serum level of ALT in the low-dose DOP group had no significant changes， drug interventions， especially high-dose DOP， lowered the levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum and down-regulated the mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.05， P<0.01）. The results of ARFI and correlation analysis showed that the YM of the liver tissue was increased in the model group （P<0.01） compared with that in the normal group， Compared with the model group， drug interventions decreased YM （P<0.01）. YM was positively correlated with the expression levels of HA， LN， PC-Ⅲ， α-SMA， Notch1， Jagged1， and Hes1s （r=0.754， 0.734， 0.801， 0.885， 0.896， 0.757， and 0.800， respectively， P<0.01）， and it had a moderate correlation with Col-Ⅳ （r=0.688， P<0.01）. ConclusionDOP can reverse HF by down-regulating the Notch1/Jagged1/Hes1 signaling pathway. YM can be used as an indicator in the assessment of the efficacy of DOP against HF.