1.Analysis of HPV Infection Characteristics and Influencing Factors for Lesion Grade in Patients with Cervical Squamous Intraepithelial Lesion and Cervical Cancer
Jingjing HAN ; Lijie ZHANG ; Ruyu CAI ; Haili LI ; He WANG ; Le DANG ; Hongda CHEN ; Ming'e LI ; Lan ZHU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):156-165
To summarize the distribution characteristics of human papillomavirus(HPV) infection types in patients with cervical squamous intraepithelial lesion(SIL) and cervical cancer(CC), and to explore the impact of HPV vaccination, HPV infection types, and general clinical data on different grades of cervical lesions. Clinical data of women attending the gynecological colposcopy clinic of Shenzhen People's Hospital from January 2020 to December 2023 were retrospectively collected. Patients with HPV genotyping records and histopathologically diagnosed SIL or CC were included and divided into three groups based on pathological results: low-grade squamous intraepithelial lesion(LSIL) group, high-grade squamous intraepithelial lesion(HSIL) group, and CC group. The distribution of high-risk HPV subtypes was analyzed among the three groups, and multivariate Logistic regression was used to identify influencing factors for high-grade cervical lesions. A total of 4162 patients were included, comprising 4057 cervical SIL patients(3317 LSIL and 740 HSIL) and 105 CC patients. The overall mean age was(39.9±11.2) years. The HPV infection rate was 95.1%(3959/4162), and 25.0%(1040/4162) of patients had received HPV vaccination. Among high-risk HPV infections, HPV 52, HPV 16, HPV 58, and HPV 18 were the most common subtypes. HPV 52 had the highest infection rate in the LSIL group(27.6%), while HPV 16 was the most prevalent in the HSIL group(45.3%) and CC group(64.9%). Multivariate Logistic regression analysis showed that HPV vaccination( HPV infection is common in patients with SIL and CC, but the distribution of high-risk HPV subtypes varies among different grades of cervical lesions. It is recommended to strengthen cervical cancer screening and monitoring of key high-risk HPV infections in older and multiparous women in Shenzhen, and to continue promoting HPV vaccination.
2.Effectiveness of posterior single-level osteotomy with 360° release and correction in treatment of osteoporotic vertebral compression fractures with moderate to severe kyphosis.
Peidong QING ; Hongda XU ; Youpeng HU ; Bin XIE ; Tieheng WANG ; Lei ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(12):1574-1579
OBJECTIVE:
To explore the effectiveness of posterior single-level osteotomy with 360° release and correction for the treatment of osteoporotic vertebral compression fractures (OVCF) complicated with moderate to severe kyphosis.
METHODS:
A retrospective analysis was conducted on 11 patients with OVCF complicated with moderate to severe kyphosis between January 2022 and March 2023. There were 4 males and 7 females with an average age of 57 years ranging from 47 to 69 years. The disease duration ranged from 3 to 15 months, with an average of 7 months. Fracture segments included T 11 in 3 cases, T 12 in 5, L 1 in 2, and L 2 in 1. The T value of lumbar spine bone density was -5.0 to -2.0, with an average of -3.5. The preoperative neurological function was grade E according to Frankel grading. The Pfirrmann classification of the intervertebral disc above the injured vertebra was grade Ⅲ in 8 cases and grade Ⅳ in 3 cases. All patients underwent posterior single-level osteotomy with 360° release and correction. The operation time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Thoracolumbar local kyphosis Cobb angle, the mean height of the functional spinal unit (FSU), the sagittal vertical axis (SVA), and the sagittal index (SI) were measured. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the improvement of pain and function before operation, at 1 month after operation, and at last follow-up.
RESULTS:
The operation successfully completed in all patients, and there was no obvious complication. The operation time ranged from 100 to 190 minutes, with an average of 153 minutes, and the intraoperative blood loss ranged from 200 to 800 mL, with an average of 468 mL. The length of hospital stay was 8-14 days (mean, 12 days). All patients were followed up 6-24 months, with an average of 12.4 months. At last follow-up, all the 11 patients had bony fusion in the osteotomy area, and there was no displacement or subsidence of the Cage, no complication such as internal fixation failure or pseudarthrosis formation was found. The Cobb angle of local thoracolumbar kyphosis, the mean height of FSU, SVA, and SI significantly improved immediately after operation and at last follow-up when compared with preoperative ones, and the VAS score and ODI also significantly improved at 1 month after operation and at last follow-up ( P<0.05); there was no significant difference in above indexes between the two time points after operation ( P>0.05).
CONCLUSION
Posterior single-level osteotomy with 360° release and correction is an effective surgical method for treating OVCF complicated with moderate to severe kyphosis, with definite early effectiveness.
Humans
;
Kyphosis/etiology*
;
Male
;
Female
;
Osteotomy/methods*
;
Middle Aged
;
Retrospective Studies
;
Aged
;
Spinal Fractures/diagnostic imaging*
;
Fractures, Compression/diagnostic imaging*
;
Osteoporotic Fractures/complications*
;
Treatment Outcome
;
Lumbar Vertebrae/injuries*
;
Thoracic Vertebrae/injuries*
;
Operative Time
;
Fracture Fixation, Internal/methods*
3.Research progress on strontium modified β-tricalcium phosphate composite biomaterials with immune regulatory properties.
Huanxi LI ; Xingyu SHAN ; Hongda WANG ; Zhimin TIAN ; Chunnuo HE ; Haoqiang ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(4):511-517
OBJECTIVE:
To review the research progress of strontium (Sr) modified β-tricalcium phosphate composite biomaterials (SrTCP) promoting osteogenesis through immune regulation, and provides reference and theoretical support for the further development and research of SrTCP bone repair materials in bone tissue engineering in the future.
METHODS:
The literature about SrTCP promoting osteogenesis through immune regulation at home and abroad in recent years was extensively reviewed, and the preparation methods, immune mechanism and application of promoting osteogenesis were summarized and analyzed.
RESULTS:
The preparation methods of SrTCP include solid-state reaction sintering method, solution combustion quenching method, direct doping method, ion substitution method, etc. SrTCP has immune regulatory effects, which can play an immune regulatory role in inducing macrophage polarization, inducing angiogenesis and anti oxidative stress to promote osteogenesis.
CONCLUSION
At present, studies have shown that SrTCP can promote bone defect repair through immune regulation. Subsequent studies can start from the control of the optimal repair concentration and release rate of Sr, and further clarify the specific mechanism of SrTCP in promoting angiogenesis and anti oxidative stress, which is helpful to develop new materials for bone defect repair.
Calcium Phosphates/pharmacology*
;
Strontium/pharmacology*
;
Biocompatible Materials/pharmacology*
;
Humans
;
Osteogenesis/drug effects*
;
Tissue Engineering/methods*
;
Bone Substitutes/pharmacology*
;
Bone Regeneration/drug effects*
;
Animals
;
Tissue Scaffolds/chemistry*
;
Neovascularization, Physiologic/drug effects*
;
Macrophages/immunology*
4.Brain PET imaging characteristics of 18F-FDG in patients with autoimmune encephalitis at different stages
Yue WANG ; Chenpeng ZHANG ; Yong HAO ; Hongda SHAO ; Mei XIN ; Yan ZHANG ; Liangrong WAN ; Yangtai GUAN ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(4):212-217
Objective:To explore the value of 18F-FDG PET brain imaging in the auxiliary diagnosis of autoimmune encephalitis (AE) before treatment, and to analyze the regional and course-related characteristics of brain metabolic changes. Methods:The 18F-FDG PET brain imaging data of 49 AE patients (26 males, 23 females, age 48.0(29.0, 61.0) years) who did not receive first-line immunotherapy were retrospectively analyzed. Patients were collected from Renji Hospital, Shanghai Jiao Tong University School of Medicine, between July 2015 and December 2023. Forty-nine age- and gender-matched healthy subjects who underwent routine physical examination at the same time period were selected as the healthy controls (HC). The statistical parametric mapping (SPM) 8 two-sample t test ( P<0.001, k=50) was used to compare the imaging results of AE patients with those of HC. The screening results were adjusted by the cluster-level family-wise error rate (FWER) for P<0.05. Metabolic abnormalities associated with AE were identified, and differences in metabolic patterns at different stages of the disease course (short: ≤1 month; medium: >1 month and ≤3 month; long: >3 month) were compared by subgroup analysis. Mann-Whitney U test was used to analyze the data. Results:In the included AE patients, regions with elevated metabolism were mainly located in the limbic lobe, insula, putamen, and amygdala ( t values: 3.18-5.07, Z values: 3.17-4.76), while local metabolic reduction was observed in the frontal, parietal, and occipital lobes ( t values: 3.18-5.43, Z values: 3.23-5.06), with most of these regions passing FWER correction. In patients with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis, local metabolism increased in the right superior temporal gyrus ( t values: 3.55-4.79, Z values: 3.67-3.86) and decreased in the left middle temporal gyrus and inferior frontal gyrus ( t values: 3.55-5.43, Z values: 3.45-4.21), but the results did not pass the FWER correction. Subgroup analysis showed that in patients with short disease course ( n=17), regions with locally elevated metabolism included the brainstem, limbic lobe, and cerebellum ( t values: 3.37-5.27, Z values: 3.52-4.44), while regions with reduced metabolism were mainly located in the frontal, parietal, and occipital lobes ( t values: 3.37-6.77, Z values: 3.34-5.30), and these abnormal results all passed FWER correction. In patients with medium ( n=7) to long ( n=25) disease course, the regions with metabolic abnormalities were significantly reduced and did not pass FWER correction. Conclusions:18F-FDG PET can accurately identify brain metabolic abnormalities in AE patients, demonstrating significant regional and course-related characteristics. Metabolic abnormalities are more pronounced in patients with short disease course, while they are relatively less obvious in patients with medium to long disease course.
5.Exploring Molecular Mechanism of Gypenoside L against Ovarian Cancer Based on Ferroptosis Pathway Mediated by Mature-tRNA-Asp-GTC/ATF3-LPCAT3
Jingxuan ZHU ; Jiao ZHAO ; Qun WANG ; Xiaofei SUN ; Jiaxin WANG ; Hongda ZHANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):107-117
ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer (OC) cells and the regulatory mechanism of gypenoside L (Gyp-L) on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 (CCK-8) assay, and the half-maximal inhibitory concentration (IC50) values of cisplatin (DDP), Gyp-L, and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs (tsRNAs) in the cells after Gyp-L intervention, and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde (MDA), glutathione (GSH), and lipid peroxide (LPO) levels were measured by colorimetry or enzyme linked immunosorbent assay (ELISA) method, Fe2+ content by FerroOrange fluorescent probe, and reactive oxygen species (ROS) content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group, a 50 µmol·L-1 Gyp-L group, and a 100 µmol·L-1 Gyp-L group. Quantitative real-time polymerase chain reaction (PCR) was performed to detect the expression of mature-tRNA-Asp-GTC, mature-tRNA-Leu-CAA, mature-mt_tRNA-Tyr-GTA_5_end, mature-tRNA-Val-CAC, mature-mt_tRNA-Glu-TTC, pre-tRNA-Arg-TCT, mature-tRNA-Asn-GTT, hydroxymethylbilane synthase (HMBS), Wnt, β-catenin, glutathione peroxidase 4 (GPX4), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf2), activating transcription factor 3 (ATF3), cystine/glutamate antiporter xCT, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Western blot was performed to detect the expression of HMBS, Wnt, β-catenin, GPX4, KEAP1, Nrf2, ATF3, xCT, LPCAT3, and ALOX15 proteins. ResultsThe 50 µmol·L-1 Gyp-L, 100 µmol·L-1 Gyp-L, DDP, 50 µmol·L-1 Gyp-L+DDP, and 100 µmol·L-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells (P<0.05) and exacerbated cell ferroptosis as reflected by the increase in the content of ROS, MDA, LPO, and Fe2+, as well as a decrease in the content of GSH (P<0.05). Compared with the control group, Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells (P<0.05, |log2Fc|>1). Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention (P<0.05). ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.
6.Exploring Molecular Mechanism of Gypenoside L against Ovarian Cancer Based on Ferroptosis Pathway Mediated by Mature-tRNA-Asp-GTC/ATF3-LPCAT3
Jingxuan ZHU ; Jiao ZHAO ; Qun WANG ; Xiaofei SUN ; Jiaxin WANG ; Hongda ZHANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):107-117
ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer (OC) cells and the regulatory mechanism of gypenoside L (Gyp-L) on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 (CCK-8) assay, and the half-maximal inhibitory concentration (IC50) values of cisplatin (DDP), Gyp-L, and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs (tsRNAs) in the cells after Gyp-L intervention, and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde (MDA), glutathione (GSH), and lipid peroxide (LPO) levels were measured by colorimetry or enzyme linked immunosorbent assay (ELISA) method, Fe2+ content by FerroOrange fluorescent probe, and reactive oxygen species (ROS) content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group, a 50 µmol·L-1 Gyp-L group, and a 100 µmol·L-1 Gyp-L group. Quantitative real-time polymerase chain reaction (PCR) was performed to detect the expression of mature-tRNA-Asp-GTC, mature-tRNA-Leu-CAA, mature-mt_tRNA-Tyr-GTA_5_end, mature-tRNA-Val-CAC, mature-mt_tRNA-Glu-TTC, pre-tRNA-Arg-TCT, mature-tRNA-Asn-GTT, hydroxymethylbilane synthase (HMBS), Wnt, β-catenin, glutathione peroxidase 4 (GPX4), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf2), activating transcription factor 3 (ATF3), cystine/glutamate antiporter xCT, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Western blot was performed to detect the expression of HMBS, Wnt, β-catenin, GPX4, KEAP1, Nrf2, ATF3, xCT, LPCAT3, and ALOX15 proteins. ResultsThe 50 µmol·L-1 Gyp-L, 100 µmol·L-1 Gyp-L, DDP, 50 µmol·L-1 Gyp-L+DDP, and 100 µmol·L-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells (P<0.05) and exacerbated cell ferroptosis as reflected by the increase in the content of ROS, MDA, LPO, and Fe2+, as well as a decrease in the content of GSH (P<0.05). Compared with the control group, Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells (P<0.05, |log2Fc|>1). Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention (P<0.05). ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.
7.Acupuncture clinical decision support system:application of AI technology in acupuncture diagnosis and treatment.
Shuxin ZHANG ; Xinyu LI ; Yanning LIU ; Xubo HONG ; Zhenhu CHEN ; Hongda ZHANG ; Jiaming HONG ; Nanbu WANG
Chinese Acupuncture & Moxibustion 2025;45(7):875-880
Artificial intelligence (AI) technology enhances the function of acupuncture clinical decision support system (CDSS) by promoting the accuracy of its diagnosis, assisting the formulation of personalized therapeutic regimen, and realizing the scientific and precise evaluation of its therapeutic effect. This paper deeply analyzes the unique advantages of AI-based acupuncture CDSS, including the intelligence and high efficiency. Besides, it points out the challenges of data security, the lack of model interpretation and the complexity of interdisciplinary cooperation in the development of acupuncture CDSS. With the continuous development and improvement of AI technology, acupuncture CDSS is expected to play a more important role in the fields of personalized medicine, telemedicine and disease prevention, and to further advance the efficiency and effect of acupuncture treatment, drive the modernization of acupuncture, and enhance its position and influence in the global healthcare system.
Humans
;
Acupuncture Therapy
;
Artificial Intelligence
;
Decision Support Systems, Clinical
8.Clinical outcomes and prognostic factors of pemphigus vulgaris and pemphigus foliaceus: A 20-year retrospective study.
Hongda LI ; Wenchao LI ; Zhenzhen WANG ; Shan CAO ; Pengcheng HUAI ; Tongsheng CHU ; Baoqi YANG ; Yonghu SUN ; Peiye XING ; Guizhi ZHOU ; Yongxia LIU ; Shengli CHEN ; Qing YANG ; Mei WU ; Zhongxiang SHI ; Hong LIU ; Furen ZHANG
Chinese Medical Journal 2025;138(10):1239-1241
9.P4HA1 mediates YAP hydroxylation and accelerates collagen synthesis in temozolomide-resistant glioblastoma.
Xueru LI ; Gangfeng YU ; Xiao ZHONG ; Jiacheng ZHONG ; Xiangyu CHEN ; Qinglong CHEN ; Jinjiang XUE ; Xi YANG ; Xinchun ZHANG ; Yao LING ; Yun XIU ; Yaqi DENG ; Hongda LI ; Wei MO ; Yong ZHU ; Ting ZHANG ; Liangjun QIAO ; Song CHEN ; Fanghui LU
Chinese Medical Journal 2025;138(16):1991-2005
BACKGROUND:
Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.
METHODS:
Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ.
RESULTS:
This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival.
CONCLUSION
P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide
;
Humans
;
Glioblastoma/drug therapy*
;
Animals
;
Mice
;
Cell Line, Tumor
;
Drug Resistance, Neoplasm/genetics*
;
YAP-Signaling Proteins
;
Hydroxylation
;
Dacarbazine/pharmacology*
;
Adaptor Proteins, Signal Transducing/metabolism*
;
Transcription Factors/metabolism*
;
Collagen/biosynthesis*
;
Collagen Type I/metabolism*
;
Prolyl Hydroxylases/metabolism*
;
Antineoplastic Agents, Alkylating/therapeutic use*
10.Functionalized self-assembled micelles enhance effect of tranexamic acid in treatment of cutaneous hyperpigmentation
Junlong QI ; Junyi LIU ; Yuzhou HE ; Wei QIANG ; Shiying ZHANG ; Qiao LIU ; Hongda ZHU
Chinese Journal of Tissue Engineering Research 2025;29(28):6061-6069
BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)%and(6.65±0.08)%,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.

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