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 robot 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 xxx Laboratory to evaluate the surgical system. RESULTS: The results showed that the accuracy of the benign and malignant tumor segmentation were 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.

New application of traditional S retractor in collecting wound flushing fluid after skin tumour resection.

After Skin tumour resection, there may be residual tumour cells on the wound surface, washing the wound surface with sterilized water can mediate tumour cell lysis and improve patient prognosis. We observed that when the patient is lying behind the operating table, both the limbs and trunk will form an inclined plane with a high centre and a low periphery. Fit the hook of the traditional S retractor onto the low end of the inclined surface, and apply appropriate pressure to make the fitting tight. This way, the flushing fluid will converge at the low end of the fitting surface and will not leak out. Combined with a negative pressure aspirator, it can reduce the splashing of flushing fluid. The traditional S retractor is common in the operating room, which is easy to operate and do not increase medical costs. The method of using a traditional S retractor to collect flushing fluid is worth further promotion.

Whether the watch-and-wait strategy has application value for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy? A network meta-analysis.

The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P < 0.05). The RS group was significantly better than the WW group in terms of the LR rate (odds ratio [OR] = 0.12, 95 % confidence interval [CI]: 0.06-0.21, P < 0.001, I2 = 0 %], 3-year DFS (OR = 1.56, 95 % CI: 1.10-2.21, P = 0.01, I2 = 38 %), and 5-year DFS (OR = 2.30, 95 % CI: 1.53-3.46, P < 0.001, I2 = 34 %). The results of network meta-analysis were also similar. After sensitivity analysis, the 5-year OS of the RS group was significantly better than that of the WW group (OR = 2.77, 95 % CI: 1.28-6.00, P = 0.009, I2 = 33 %). Nevertheless, neither regression analysis nor subgroup analysis provided meaningful results. However, the cumulative meta-analysis of LR, DM, and 3- and 5-year DFS revealed significant turning points (P < 0.05). Our meta-analysis recommends using the WW strategy for patients with cCR having poor underlying conditions and high surgical risk; however, there is a risk of higher LR and worse survival after 3 years.

Covalently Functionalized Nanopores for Highly Selective Separation of Monovalent Ions.

Biological ion channels possess prominent ion transport performances attributed to their critical chemical groups across the continuous nanoscale filters. However, it is still a challenge to imitate these sophisticated performances in artificial nanoscale systems. Herein, this work develops the strategy to fabricate functionalized graphene nanopores in pioneer based on the synergistic regulation of the pore size and chemical properties of atomically thin confined structure through decoupling etching combined with in situ covalent modification. The modified graphene nanopores possess asymmetric ion transport behaviors and efficient monovalent metal ions sieving (K+ /Li+ selectivity ≈48.6). Meanwhile, it also allows preferential transport for cations, the resulting membranes exhibit a K+ /Cl- selectivity of 76 and a H+ /Cl- selectivity of 59.3. The synergistic effects of steric hindrance and electrostatic interactions imposing a higher energy barrier for Cl- or Li+ across nanopores lead to ultra-selective H+ or K+ transport. Further, the functionalized graphene nanopores generate a power density of 25.3 W m-2 and a conversion efficiency of 33.9%, showing potential application prospects in energy conversion. The theoretical studies quantitatively match well with the experimental results. The feasible preparation of functionalized graphene nanopores paves the way toward direct investigation on ion transport mechanism and advanced design in devices.

Preanchoring Enabled Directional Modification of Atomically Thin Membrane for High-Performance Osmotic Energy Generation.

Salinity gradient energy is an environmentally friendly energy source that possesses potential to meet the growing global energy demand. Although covalently modified nanoporous graphene membranes are prospective candidates to break the trade-off between ion selectivity and permeability, the random reaction sites and inevitable defects during modification reduce the reaction efficiency and energy conversion performance. Here, we developed a preanchoring method to achieve directional modification near the graphene nanopores periphery. Numerical simulation revealed that the improved surface charge density around nanopores results in exceptional K+/Cl- selectivity and osmotic energy conversion performance, which agreed well with experimental results. Ionic transport measurements showed that the directionally modified graphene membranes achieved an outstanding power density of 81.6 W m-2 with an energy conversion efficiency of 35.4% under a 100-fold salinity gradient, outperforming state-of-the-art graphene-based nanoporous membranes. This work provided a facile approach for precise modification of nanoporous graphene membranes and opened up new ways for osmotic power harvesting.

Study on correlation between TBM tailings gradation and granitic gneiss surrounding rock stability.

In the process of double-shield TBM excavation, it is difficult to directly observe and test the characteristics of the surrounding rock. In this paper, the screening test of the different type tailings in the wet state was carried out to obtain the gradation curve and curve evaluation index. Combining with the excavation parameters and the surrounding rock characteristics of the tailings, a comprehensive analysis was carried out to establish the evaluation system among with the tailings gradation characteristics, lithology characteristics and excavation parameters. The results showed that: Sparsely fissured rock: the tailings are extensional fractures, the tailings gradation curve is inverse "S" type and gentle, and the evaluation index value: (1.50 > lg(Cu) > 1.35), (1.90 > Cc > 1.10). Broken surrounding rock: the curve is "L" type and steep, the content of coarse particles is much more than that of fine particles and (1.10 > lg(Cu) > 1.00), (2.60 > Cc > 2.40). Fractured rock: the curve is "Step" type, the tailings particles lack the middle particle size, the minerals are mostly weathered, (2.15 > lg(Cu )> 1.95), (0.09 > Cc > 0.07). The research results have good applicability to the surrounding rock stability evaluation of the example tunnel, which verifies the feasibility of the method.

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.

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.

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.

Global trends and prospects in health economics of robotic surgery: a bibliometric analysis.

BACKGROUND: Over 10 million robotic surgeries have been performed. However, the cost and benefit of robotic surgery need to be evaluated to help hospitals, surgeons, patients, and payers make proper choices, making a health economic analysis necessary. The authors revealed the bibliometric profile in the field of health economics of robotic surgery to prompt research development and guide future studies. MATERIALS AND METHODS: The Web of Science Core Collection scientific database was searched for documents indexed from 2003 to 31 December 2022. Document types, years, authors, countries, institutions, journal sources, references, and keywords were analyzed and visualized using the Bibliometrix package, WPS Office software, Microsoft PowerPoint 2019, VOSviewer software (version 1.6.18), ggplot2, and Scimago Graphica. RESULTS: The development of the health economics of robotic surgery can be divided into three phases: slow-growing (2003-2009), developing (2010-2018), and fast-developing (2019-2022). J.C.H. and S.L.C. were the most active and influential authors, respectively. The USA produced the most documents, followed by China, and Italy. Korea had the highest number of citations per document. Surgical Endoscopy and Other Interventional Techniques accepted most documents, whereas Annals of Surgery, European Urology, and Journal of Minimally Invasive Gynecology had the highest number of citations per document. The Journal of Robotic Surgery is promising. The most-cited document in this field is New Technology and Health Care Costs - The Case of Robot-Assisted Surgery in 2010. The proportion of documents on urology is decreasing, while documents in the field of arthrology are emerging and flourishing. CONCLUSION: Research on the health economics of robotic surgery has been unbalanced. Areas awaiting exploration have been identified. Collaboration between scholars and coverage with provisions for evidence development by the government is needed to learn more comprehensively about the health economics of robotic surgery.

Differentiating tumour progression from pseudoprogression in glioblastoma patients: a monoexponential, biexponential, and stretched-exponential model-based DWI study.

BACKGROUND: To investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in differentiating tumour progression from pseudoprogression in glioblastoma patients. METHODS: Forty patients with pathologically confirmed glioblastoma exhibiting enhancing lesions after completion of chemoradiation therapy were enrolled in the study, which were then classified as tumour progression and pseudoprogression. All patients underwent conventional and multi-b diffusion-weighted MRI. The apparent diffusion coefficient (ADC) from a monoexponential model, the true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched-exponential model were compared between tumour progression and pseudoprogression groups. Receiver operating characteristic curves (ROC) analysis was used to investigate the diagnostic performance of different DWI parameters. Interclass correlation coefficient (ICC) was used to evaluate the consistency of measurements. RESULTS: The values of ADC, D, DDC, and α values were lower in tumour progression patients than that in pseudoprogression patients (p < 0.05). The values of D* and f were higher in tumour progression patients than that in pseudoprogression patients (p < 0.05). Diagnostic accuracy for differentiating tumour progression from pseudoprogression was highest for α(AUC = 0.94) than that for ADC (AUC = 0.91), D (AUC = 0.92), D* (AUC = 0.81), f (AUC = 0.75), and DDC (AUC = 0.88). CONCLUSIONS: Multi-b DWI is a promising method for differentiating tumour progression from pseudoprogression with high diagnostic accuracy. In addition, the α derived from stretched-exponential model is the most promising DWI parameter for the prediction of tumour progression in glioblastoma patients.

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.

Essential Oil Nanoemulsion Hydrogel with Anti-Biofilm Activity for the Treatment of Infected Wounds.

The formation of a bacterial biofilm on an infected wound can impede drug penetration and greatly thwart the healing process. Thus, it is essential to develop a wound dressing that can inhibit the growth of and remove biofilms, facilitating the healing of infected wounds. In this study, optimized eucalyptus essential oil nanoemulsions (EEO NEs) were prepared from eucalyptus essential oil, Tween 80, anhydrous ethanol, and water. Afterward, they were combined with a hydrogel matrix physically cross-linked with Carbomer 940 (CBM) and carboxymethyl chitosan (CMC) to prepare eucalyptus essential oil nanoemulsion hydrogels (CBM/CMC/EEO NE). The physical-chemical properties, in vitro bacterial inhibition, and biocompatibility of EEO NE and CBM/CMC/EEO NE were extensively investigated and the infected wound models were proposed to validate the in vivo therapeutic efficacy of CBM/CMC/EEO NE. The results showed that the average particle size of EEO NE was 15.34 ± 3.77 nm with PDI ˂ 0.2, the minimum inhibitory concentration (MIC) of EEO NE was 15 mg/mL, and the minimum bactericidal concentration (MBC) against S. aureus was 25 mg/mL. The inhibition and clearance of EEO NE against S. aureus biofilm at 2×MIC concentrations were 77.530 ± 7.292% and 60.700 ± 3.341%, respectively, demonstrating high anti-biofilm activity in vitro. CBM/CMC/EEO NE exhibited good rheology, water retention, porosity, water vapor permeability, and biocompatibility, meeting the requirements for trauma dressings. In vivo experiments revealed that CBM/CMC/EEO NE effectively promoted wound healing, reduced the bacterial load of wounds, and accelerated the recovery of epidermal and dermal tissue cells. Moreover, CBM/CMC/EEO NE significantly down-regulated the expression of two inflammatory factors, IL-6 and TNF-α, and up-regulated three growth-promoting factors, TGF-ß1, VEGF, and EGF. Thus, the CBM/CMC/EEO NE hydrogel effectively treated wounds infected with S. aureus, enhancing the healing process. It is expected to be a new clinical alternative for healing infected wounds in the future.

Immune-related risk score: An immune-cell-pair-based prognostic model for cutaneous melanoma.

Background: Melanoma is among the most malignant immunologic tumor types and is associated with high mortality. However, a considerable number of melanoma patients cannot benefit from immunotherapy owing to individual differences. This study attempts to build a novel prediction model of melanoma that fully considers individual differences in the tumor microenvironment. Methods: An immune-related risk score (IRRS) was constructed based on cutaneous melanoma data from The Cancer Genome Atlas (TCGA). Single-sample gene set enrichment analysis (ssGSEA) was used to calculate immune enrichment scores of 28 immune cell signatures. We performed pairwise comparisons to obtain scores for cell pairs based on the difference in the abundance of immune cells within each sample. The resulting cell pair scores, in the form of a matrix of relative values of immune cells, formed the core of the IRRS. Results: The area under the curve (AUC) for the IRRS was over 0.700, and when the IRRS was combined with clinical information, the AUC reached 0.785, 0.817, and 0.801 for the 1-, 3-, and 5-year survival, respectively. Differentially expressed genes between the two groups were enriched in staphylococcal infection and estrogen metabolism pathway. The low IRRS group showed a better immunotherapeutic response and exhibited more neoantigens, richer T-cell receptor and B-cell receptor diversity, and higher tumor mutation burden. Conclusion: The IRRS enables a good prediction of prognosis and immunotherapy effect, based on the difference in the relative abundance of different types of infiltrating immune cells, and could provide support for further research in melanoma.

Wider indications and more efficient drug delivery: A bibliometric analysis and visualization of photodynamic therapy in skin cancer.

BACKGROUND: Photodynamic therapy (PDT) has been widely accepted in keratocyte carcinoma and an increasing number of literatures concerning PDT in skin cancer is published. But a detailed examination of publication patterns of PDT in skin cancer has not yet been carried out. METHODS: Bibliographies were retrieved from Web of Science Core Collection restricted the publication date from January 1, 1985 to December 31, 2021. The search terms were photodynamic therapy and skin cancer. Visualization analysis and statistical analysis were performed by VOSviewer (Version 1.6.13), R software (Version 4.1.2) and Scimago Graphica (Version 1.0.15). RESULTS: 3248 documents were selected for analysis. The results showed that the number of annual publications related to PDT in skin cancer was gradually increased and would continue to increase in the future. The results illustrated that "melanoma", "nanoparticles", "drug-delivery", "mechanism", "delivery" and "in-vitro" are newly occurred topics. The most prolific country was the United States and the most productive institution was the University of Sao Paulo in Brazil. German researcher Szeimies RM published the most papers related to PDT in skin cancer. British Journal of Dermatology was the most popular journal in this field. CONCLUSION: The topic that PDT in skin cancer is a heated issue. Our study revealed the bibliometric result of the field, which might provide the prospects for further research. We recommend future investigations focusing on PDT in treating melanoma, innovation of photosensitizer, improvement of drug delivery and the mechanism of PDT in skin cancer.

Targets and mechanisms of Alpinia oxyphylla Miquel fruits in treating neurodegenerative dementia.

The dried and ripe fruits of Alpinia oxyphylla and ripe fruits of Alpinia oxyphylla Miquel (AO) have the effects of tonifying kidney-essence and nourishing intelligence and thus have been widely used in treating dementia. Alzheimer's disease (AD) is a typical form of neurodegenerative dementia with kidney-essence deficiency in Traditional Chinese Medicine (TCM). So far, there is a lack of systematic studies on the biological basis of tonifying kidney-essence and nourishing intelligence and the corresponding phytochemicals. In this study, we investigated the targets of AO in tonifying kidney-essence and nourishing intelligence based on the key pathophysiological processes of neurodegenerative dementia. According to ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry data and Lipinski's rule of five, 49 bioactive phytochemicals from AO were identified, and 26 of them were found to target 168 key molecules in the treatment of neurodegenerative dementia. Nine phytochemicals of AO were shown to target acetylcholinesterase (ACHE), and 19 phytochemicals were shown to target butyrylcholinesterase (BCHE). A database of neurodegenerative dementia with kidney-essence deficiency involving 731 genes was constructed. Furthermore, yakuchinone B, 5-hydroxy-1,7-bis (4-hydroxy-3-methoxyphenyl) heptan-3-one (5-HYD), oxyhylladiketone, oxyphyllacinol, butyl-ß-D-fructopyranoside, dibutyl phthalate, chrysin, yakuchinone A, rhamnetin, and rhamnocitrin were identified as the key phytochemicals from AO that regulate the pathogenesis of neurodegenerative dementia in a multitargeted manner. The approach of studying the pharmacological mechanism underlying the effects of medicinal plants and the biological basis of TCM syndrome may be helpful in studying the translation of TCM.

[Network pharmacology-based study of the therapeutic mechanism of resveratrol for Alzheimer's disease].

OBJECTIVE: To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology. METHODS: We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3ß (GSK3ß) and p-GSK3ß in response to RES treatment using Western blotting. RESULTS: We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to ß-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 µmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3ß activity (P < 0.001). CONCLUSIONS: RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies via a direct action on Aß and Tau pathological processes.