High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage.

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.

Exploring the influence of transformer-based multimodal modeling on clinicians' diagnosis of skin diseases: A quantitative analysis.

Objectives: The study aimed to propose a multimodal model that incorporates both macroscopic and microscopic images and analyze its influence on clinicians' decision-making with different levels of experience. Methods: First, we constructed a multimodal dataset for five skin disorders. Next, we trained unimodal models on three different types of images and selected the best-performing models as the base learners. Then, we used a soft voting strategy to create the multimodal model. Finally, 12 clinicians were divided into three groups, with each group including one director dermatologist, one dermatologist-in-charge, one resident dermatologist, and one general practitioner. They were asked to diagnose the skin disorders in four unaided situations (macroscopic images only, dermatopathological images only, macroscopic and dermatopathological images, all images and metadata), and three aided situations (macroscopic images with model 1 aid, dermatopathological images with model 2&3 aid, all images with multimodal model 4 aid). The clinicians' diagnosis accuracy and time for each diagnosis were recorded. Results: Among the trained models, the vision transformer (ViT) achieved the best performance, with accuracies of 0.8636, 0.9545, 0.9673, and AUCs of 0.9823, 0.9952, 0.9989 on the training set, respectively. However, on the external validation set, they only achieved accuracies of 0.70, 0.90, and 0.94, respectively. The multimodal model performed well compared to the unimodal models, achieving an accuracy of 0.98 on the external validation set. The results of logit regression analysis indicate that all models are helpful to clinicians in making diagnostic decisions [Odds Ratios (OR) > 1], while metadata does not provide assistance to clinicians (OR < 1). Linear analysis results indicate that metadata significantly increases clinicians' diagnosis time (P < 0.05), while model assistance does not (P > 0.05). Conclusions: The results of this study suggest that the multimodal model effectively improves clinicians' diagnostic performance without significantly increasing the diagnostic time. However, further large-scale prospective studies are necessary.

Mild photothermal therapy assist in promoting bone repair: Related mechanism and materials.

Achieving precision treatment in bone tissue engineering (BTE) remains a challenge. Photothermal therapy (PTT), as a form of precision therapy, has been extensively investigated for its safety and efficacy. It has demonstrated significant potential in the treatment of orthopedic diseases such as bone tumors, postoperative infections and osteoarthritis. However, the high temperatures associated with PTT can lead to certain limitations and drawbacks. In recent years, researchers have explored the use of biomaterials for mild photothermal therapy (MPT), which offers a promising approach for addressing these limitations. This review provides a comprehensive overview of the mechanisms underlying MPT and presents a compilation of photothermal agents and their utilization strategies for bone tissue repair. Additionally, the paper discusses the future prospects of MPT-assisted bone tissue regeneration, aiming to provide insights and recommendations for optimizing material design in this field.

Bacteria-Targeted Combined with Photothermal/NO Nanoparticles for the Treatment and Diagnosis of MRSA Infection In Vivo.

Currently, undeveloped diagnosis and delayed treatment of bacteria-infected sites in vivo not only expand the risk of tissue infection but are also a major clinical cause of multiple drug-resistant bacterial infections. Herein, an efficient nanoplatform for near-infrared (NIR)-light-controlled release and bacteria-targeted delivery of nitric oxide (NO) combined with photothermal therapy (PTT) is presented. Using maltotriose-decorated mesoporous polydopamine (MPDA-Mal) and BNN6, a smart antibacterial (B@MPDA-Mal) is developed to combine bacterial targeting, gas-controlled release, and PTT. Utilizing bacteria's unique maltodextrin transport system, B@MPDA-Mal can accurately distinguish bacterial infection from sterile inflammation and target the bacteria-infected sites for efficient drug enrichment. Moreover, NIR-light causes MPDA to generate heat, which not only effectively induces BNN6 to produce NO, but also raises the temperature to harm the bacteria further. NO/photothermal combination therapy effectively eliminates biofilm and drug-resistant bacteria. The myositis model of methicillin-resistant Staphylococcus aureus infection is established and indicates that B@MPDA-Mal can successfully eradicate inflammation and abscesses in mice. Meanwhile, magnetic resonance imaging technology is used to monitor the treatment procedure and healing outcomes. Given the aforementioned advantages, the smart antibacterial nanoplatform B@MPDA-Mal can be used as a potential therapeutic tool in the biomedical field against drug-resistant bacterial infections.

Dynamic nitric oxide/drug codelivery system based on polyrotaxane architecture for effective treatment of Candida albicans infection.

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. STATEMENT OF SIGNIFICANCE: A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.

Superficial and multiple calcifications and ulceration associate with intraplaque hemorrhage in the carotid atherosclerotic plaque.

OBJECTIVE: Intraplaque hemorrhage (IPH) and ulceration of carotid atherosclerotic plaques have been associated with vulnerability while calcification has been conventionally thought protective. However, studies suggested calcification size and location may increase plaque vulnerability. This study explored the association between calcium configurations and ulceration with IPH. METHODS: One hundred thirty-seven consecutive symptomatic patients scheduled for carotid endarterectomy were recruited. CTA and CTP were performed prior to surgery. Plaque samples were collected for histology. According to the location, calcifications were categorized into superficial, deep and mixed types; according to the size and number, calcifications were classified as thick and thin, multiple and single. RESULTS: Seventy-one plaques had IPH (51.8%) and 83 had ulceration (60.6%). The appearance of IPH and ulceration was correlated (r = 0.49; p < 0.001). The incidence of multiple, superficial and thin calcifications was significantly higher in lesions with IPH and ulceration compared with those without. After adjusting factors including age, stenosis and ulceration, the presence of calcification [OR (95% CI), 3.0 (1.1-8.2), p = 0.035], multiple calcification [3.9 (1.4-10.9), p = 0.009] and superficial calcification [3.4 (1.1-10.8), p = 0.001] were all associated with IPH. ROC analysis showed that the AUC of superficial and multiple calcifications in detecting IPH was 0.63 and 0.66, respectively (p < 0.05). When the ulceration was combined, AUC increased significantly to 0.82 and 0.83, respectively. Results also showed that patients with lesions of both ulceration and IPH have significantly reduced brain perfusion in the area ipsilateral to the infarction. CONCLUSIONS: Superficial and multiple calcifications and ulceration were associated with carotid IPH, and they may be a surrogate for higher risk lesions. KEY POINTS: • CTA-defined superficial and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of intraplaque hemorrhage. • The combination of superficial and multiple calcifications and ulceration is highly predictive of carotid intraplaque hemorrhage. • Patients with lesions of both ulceration and intraplaque hemorrhage have significantly reduced brain perfusion in the area ipsilateral to the infarction.

[Eighteen years activity in prevention of blindness in the district of Shunyi, Beijing].

OBJECTIVE: To investigate how the urban tertiary hospital and medical research unit cooperate with rural basic medical unit in creating the model zone in prevention of blindness. METHODS: Peking Union Medical College Hospital (PUMCH) and Shunyi District Bureau of Public Health exerted their advantages to persist and popularize the program for prevention of blindness. A collaborative program in prevention of blindness was conducted by PUMCH and Shunyi District Bureau of Public Health. The targeted subjects were the population in Shunyi District of Beijing. An epidemiological survey of eye diseases was performed in 1984. A program for prevention of blindness was established and conducted afterward. RESULTS: The status of blindness in Shunyi District was unveiled by the eye epidemiological survey of eye diseases in 1984. Three-level primary eye care network and referring and treatment system for cataract blindness was established since 1987. The survey showed that the priority in prevent of blindness is surgical treatment of cataract in the area. The evaluation of the program in prevention and treatment for blindness in 1996 showed that the prevalence of blindness was decreased even it is increasing in both the total population and aged people. CONCLUSION: The cooperation in urban tertiary hospital, medical research unit and basic health care unit, and combination in research and medical practice in prevention of blindness can promote development in the prevention of blindness and possible reverse the tendency of blindness increase.