Cavitation-on-a-Chip Enabled Size-Specific Liposomal Drugs for Selective Pharmacokinetics and Pharmacodynamics.

The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.

Preoperative Ultrasound-Guided Incisional Biopsy Enhances the Pathological Accuracy of Incisional Biopsy of Cutaneous Melanoma: A Prospective Clinical Trial in Chinese Patients.

OBJECTIVES: To assess the feasibility of preoperative ultrasound (US)-guided incisional biopsy through a prospective controlled clinical trial. METHODS: This was a prospective, double-arm, single-center study of Chinese patients. Thirty patients were enrolled in the study. Fourteen patients received incisional biopsies for which the choice of biopsy area relied on a clinical evaluation, and 16 patients received incisional biopsies for which the choice of biopsy area relied on a US-guided evaluation. The following procedure was used in the US-guided incisional biopsy group: 1) clinical and dermoscopic evaluation of skin lesions; 2) US examination; 3) incisional biopsy; 4) surgical excision; and 5) histopathological examination. The same procedure was used in the non-US-guided group except without US examination. RESULTS: In the non-US-guided group, the mean tumor thicknesses obtained from incisional biopsy and postoperative histopathological examination were 2.1 and 4.1 mm, respectively. Seven melanomas were underestimated by incisional biopsy, resulting in margins narrower than currently recommended. In the US-guided group, the mean tumor thicknesses obtained from US, incisional biopsy, and postoperative histopathological examination were 3.4, 2.9, and 2.7 mm, respectively. In only 3 melanomas was the tumor thickness of the incisional biopsy less than that of the postoperative histopathological examination, demonstrating that US-guided biopsy obtains the maximum thickness area. CONCLUSIONS: Preoperative US-guided incisional biopsy can enhance the pathological accuracy of incisional biopsy, which may allow us to better perform surgical excision with safe peripheral surgical margins.

Dermabrasion combined with photodynamic therapy: a new option for the treatment of non-melanoma skin cancer.

Non-melanoma skin cancer (NMSC) is the most common malignancy. Photodynamic therapy (PDT) is effective for the treatment of certain NMSCs. However, the clinical response rates of some NMSCs to single PDT are still far from ideal. The reason may be that PDT has shown limited efficacy in managing thicker NMSCs. To explore the efficacy and safety of dermabrasion combined with PDT (D-PDT) for the treatment of NMSCs. This was a retrospective, single-arm, multi-centre study. In total, 172 tumours from 40 patients were treated with D-PDT during the study period. The mean follow-up period was 40 months (range 15-110 months). D-PDT was performed with 633-nm red light at 80 m W/cm2 after lesion dermabrasion and 4 h of photosensitizer exposure. Six nodular basal cell carcinomas (nBCCs) from 6 patients, 9 squamous cell carcinomas (SCCs) from 9 patients, 17 Bowen diseases (BDs) from 10 patients and 140 actinic keratoses (AKs) from 15 patients treated with D-PDT were examined in this study. Only two patients with three AKs experienced recurrence over 12 months. The mean final follow-up periods of patients with AKs, BDs, nBCCs and SCCs were 30, 33, 45 and 60 months, respectively. Thirty-four of the 40 patients treated with D-PDT reported excellent or good cosmetic results. The mean Dermatology Life Quality Index (DLQI) scores of the patients improved significantly after treatment (estimated MD 9.72 [95% CI 8.69 to 10.75]; p < 0.001). D-PDT is a safe, cosmetic and effective treatment that could be a new candidate therapeutic for NMSC.

The Classification of Six Common Skin Diseases Based on Xiangya-Derm: Development of a Chinese Database for Artificial Intelligence.

BACKGROUND: Skin and subcutaneous disease is the fourth-leading cause of the nonfatal disease burden worldwide and constitutes one of the most common burdens in primary care. However, there is a severe lack of dermatologists, particularly in rural Chinese areas. Furthermore, although artificial intelligence (AI) tools can assist in diagnosing skin disorders from images, the database for the Chinese population is limited. OBJECTIVE: This study aims to establish a database for AI based on the Chinese population and presents an initial study on six common skin diseases. METHODS: Each image was captured with either a digital camera or a smartphone, verified by at least three experienced dermatologists and corresponding pathology information, and finally added to the Xiangya-Derm database. Based on this database, we conducted AI-assisted classification research on six common skin diseases and then proposed a network called Xy-SkinNet. Xy-SkinNet applies a two-step strategy to identify skin diseases. First, given an input image, we segmented the regions of the skin lesion. Second, we introduced an information fusion block to combine the output of all segmented regions. We compared the performance with 31 dermatologists of varied experiences. RESULTS: Xiangya-Derm, as a new database that consists of over 150,000 clinical images of 571 different skin diseases in the Chinese population, is the largest and most diverse dermatological data set of the Chinese population. The AI-based six-category classification achieved a top 3 accuracy of 84.77%, which exceeded the average accuracy of dermatologists (78.15%). CONCLUSIONS: Xiangya-Derm, the largest database for the Chinese population, was created. The classification of six common skin conditions was conducted based on Xiangya-Derm to lay a foundation for product research.

Association between alopecia areata, anxiety, and depression: Insights from a bidirectional two-sample Mendelian randomization study.

BACKGROUND: As research progresses, there has been growing interest in the association between Alopecia areata (AA) and anxiety, as well as depression. However, there have been limited reports on the genetic variation level of AA in relation to mental disorders. METHOD: We performed large-scale Two sample Mendelian randomization (MR) analyses to examine whether there is a association between AA with anxiety and depression. The data utilized for AA analysis were sourced from the FinnGen release 9 databases, including 682 cases and 361,822 controls. Summary statistics for major depression disorder (MDD) were obtained from a genome-wide meta-analysis dataset, incorporating 170,756 cases and 329,443 controls. The anxiety disorder data was conducted by the Anxiety Neuro Genetics Study Consortium, including 5580 cases and 11,730 controls. We employed four distinct approaches, including MR-Egger, weighted median, random-effect inverse variance weighted (IVW), and weighted mode, to conduct the MR analysis. RESULTS: Genetic liability to AA was associated with an increased risk of Major depression disorder (MDD) and anxiety demonstrated an odds ratio (OR) of 1.01 (ßivw = 0.011, PIVW = 0.023) and OR of 1.16 (ßivw = 0.150, PIVW = 0.002). Upon conducting the Bonferroni correction, the P-values were 0.046 and 0.004, respectively. For reverse analysis, we observed no significant association between anxiety and MDD with the risk of AA. CONCLUSIONS: Our research unveil a unidirectional causal association whereby AA exerts a risk effect against MDD and anxiety, which serves as a valuable complement to prior meta-analyses, enriching the existing body of knowledge on the subject matter.

Corrigendum: The utility of high-frequency 18 MHz ultrasonography for preoperative evaluation of acral melanoma thickness in Chinese patients.

[This corrects the article DOI: 10.3389/fonc.2023.1185389.].

A real-time augmented reality system integrated with artificial intelligence for skin tumor surgery: experimental study and case series.

BACKGROUND: Skin tumors affect many people worldwide, and surgery is the first treatment choice. Achieving precise preoperative planning and navigation of intraoperative sampling remains a problem and is excessively reliant on the experience of surgeons, especially for Mohs surgery for malignant tumors. MATERIALS AND METHODS: To achieve precise preoperative planning and navigation of intraoperative sampling, we developed a real-time augmented reality (AR) surgical system integrated with artificial intelligence (AI) to enhance three functions: AI-assisted tumor boundary segmentation, surgical margin design, and navigation in intraoperative tissue sampling. Non-randomized controlled trials were conducted on manikin, tumor-simulated rabbits, and human volunteers in Hunan Engineering Research Center of Skin Health and Disease Laboratory to evaluate the surgical system. RESULTS: The results showed that the accuracy of the benign and malignant tumor segmentation was 0.9556 and 0.9548, respectively, and the average AR navigation mapping error was 0.644 mm. The proposed surgical system was applied in 106 skin tumor surgeries, including intraoperative navigation of sampling in 16 Mohs surgery cases. Surgeons who have used this system highly recognize it. CONCLUSIONS: The surgical system highlighted the potential to achieve accurate treatment of skin tumors and to fill the gap in global research on skin tumor surgery systems.

Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer.

Background: Some retrospective studies reported that psoriasis (PsO) and psoriatic arthritis (PsA) may have been associated with an elevated risk of skin cancer. The causal associations among them remain unclear. Objectives: To evaluate the causal association of among both PsO and PsA, and skin cancer. Methods: We performed large-scale two-sample and Multivariate Mendelian randomization analyses to examine whether there is a causal relationship between PsO and PsA, and skin cancer, encompassing basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM). Results: Genetically predicted PsO, per log-odds ratio increase, showed no significant association with the risk of BCC, cSCC, and CM. The odds ratios (with corresponding 95% confidence intervals) for BCC, cSCC, and CM were 1.00 (0.99,1.01) (PIvw = 0.990), 0.94(0.89, 1.00) (PIvw = 0.065), and 0.99 (0.98, 1.01) (PIvw = 0.239), respectively. PsA showed a significant association with a decreased risk of BCC, with odds ratios (with corresponding 95% confidence intervals) of 1.00 (1.00, 1.00) (PIvw = 0.214) and 1.00 (1.00, 1.00) (PIvw = 0.477), respectively. Univariate analysis of the FinnGen database demonstrated PsA did exhibit a significant association with the decrease risk of BCC, with an odds ratio of 0.94(0.90,0.99) (PIvw = 0.016). However, this association disappeared after other risk factors were adjusted. Conclusions: Our findings suggest no causal association between PsO and PsA and the genetic risk of skin cancer. Further observational studies are required to elucidate the relationship among PsO, PsA, and skin cancer.

Investigating the gut microbiota's influence on psoriasis and psoriatic arthritis risk: a Mendelian randomization analysis.

Background: Numerous investigations have revealed the interplay between gut microbiota (GM) and psoriasis (Ps) and psoriatic arthritis (PsA). However, the causal relationship between them remains unknown. Methods: We curated a collection of genetic variants (P < 1 × 10-5) associated with GM (n = 18 340) derived from the MiBioGen study. To explore the intricate relationship between GM and Ps as well as PsA, we harnessed the comprehensive resources of the FinnGen database, encompassing a vast cohort of individuals, including 4510 Ps cases and 212 242 controls and 1637 PsA cases and 212 242 controls. Mendelian randomization (MR) was used, including an inverse variance weighting method, followed by a sensitivity analysis to verify the robustness of the results. Results: For Ps, some bacterial taxa, including Lactococcus, Ruminiclostridium 5, and Eubacterium fissicatena, were identified as risk factors; but Odoribacter demonstrated a protective effect against Ps. In the case of PsA, Lactococcus, Verrucomicrobiales, Akkermansia, Coprococcus 1, and Verrucomicrobiaceae were identified as risk factors; Odoribacter and Rikenellaceae exhibited a protective effect against the development of PsA. Conclusion: Our study establishes a causal link between the GM and Ps and PsA. These findings provide insights into the underlying mechanisms and suggest potential therapeutic targets.

Global trends in the health economics field of PD-1/PD-L1 inhibitors: A bibliometric and visualized study.

Inhibitors of programmed cell death protein 1 and its associated ligand (PD-L1) are widely used in cancer treatment. However, medical costs and benefits of PD-1/PD-L1 inhibitors need attention owing to differences in response rates among individuals. This study explored global trends in the health economics field of PD-1/PD-L1 inhibitors to enhance their worldwide development. Bibliometric analysis of all documents currently indexed in Web of Science Core Collection from inception to 2022 was performed. Publication year, authors, countries, institutes, and journals were analyzed by Bibliometrix package (version 3.2.1) in R (version 4.1.3). CiteSpace (version 6.1.R6) and VOSviewer (version 1.6.18) were used to analyze burst words, co-authorship of institutes, co-cited journals, and co-cited references, while figures were mainly drawn by Ggplot2 package (version 3.3.5) in R (version 4.1.3) and SCImago Graphica Beta (version 1.0.23). A total of 2020 documents related to the health economics of PD-1/PD-L1 inhibitors were identified, and 1,204 documents met the selection criteria for inclusion in the study. A rapid increase in the number of publications since 2019 was observed, but this increase stopped in 2022, revealing research saturation in the field. Value in Health (166 publications, 13.79% of total documents) had the most publications, while New England Journal of Medicine (2,890 co-citations) was the most co-cited journal. The United States was the leading contributor in this field with 506 publications and the top two productive institutes globally. The main hot topics included the cost-effectiveness of treatment with PD-1 and/or PD-L1 inhibitors, and the comparison between the cost-effectiveness of PD-/PD-L1 inhibitors and other drugs. There were substantial differences between developed and developing countries in the health economics field of PD-1 and/or PD-L1 inhibitors. The cost-effectiveness analysis of combined treatment with PD-1/PD-L1 inhibitors and other drugs warrants further attention. Findings from this study may provide governments and pharmaceutical companies with a strong reference for future research.

The utility of high-frequency 18 MHz ultrasonography for preoperative evaluation of acral melanoma thickness in Chinese patients.

Background: Despite the increasing use of preoperative ultrasound evaluation for melanoma, there is limited research on the use of this technique for Acral Melanoma (AM). Methods: This retrospective study analyzed the electronic medical records of patients who underwent preoperative evaluation for cutaneous melanoma maximum thickness using an 18 MHz probe and histopathological examination between December 2017 and March 2021 at the Department of Dermatology in Xiangya Hospital, Central South University. Results: A total of 105 patients were included in the study. The mean tumor thickness was 3.9 mm (s.d., 2.3), with 63% of the specimens showing ulceration and 44 patients showing lymph node metastasis. The results showed a good correlation between the high-frequency ultrasonography (HFUS) and histopathological thickness measurements, with a Spearman's correlation coefficient of 0.83 [(95% CI 0.73-0.90) (P < 0.001)]. The positive predictive value (PPV) of sonography in identifying tumor thickness was also found to be high. Conclusion: Our study suggests that high-frequency 18 MHz ultrasonography is an effective tool for the preoperative evaluation of AM thickness. The HFUS measurements correlated well with the histopathological thickness measurements, making it a valuable and reliable method for clinicians to assess the thickness of melanoma lesions preoperatively.