The development of effective therapeutic strategies for bone regeneration and repair has proven to be highly challenging due to the sluggish and unpredictable nature of the healing process. Under pathological conditions, impaired cellular function can lead to poor biomineralization and compromised bone healing, resulting in various failures. Exosomes, as potent intercellular communicators capable of delivering diverse bioactive cargo, offer significant therapeutic promise. However, the lack of comprehensive understanding of their roles in the bone healing microenvironment and biomaterial design poses challenges for exosome-based therapies. This review provides the essential biological context for exosome application in bone regeneration, with a dual focus. First, we elucidate the pivotal roles of exosomes in mediating bone microenvironmental crosstalk, emphasizing their critical involvement in immunomodulation (eg, macrophage polarization), osteogenesis-angiogenesis coupling, osteoclast-osteoblast balance, neuro-skeletal communication, and dynamic extracellular matrix remodeling, rather than merely listing cell-specific functions. Second, building on this foundation, we summarize the rationale for engineering exosomal biomaterial designs. This includes strategies for exosome optimization (eg, targeting modifications, cargo loading, parental cell stimulation) and their integration with functional scaffolds to modulate the identified crosstalk pathways and create a conducive microenvironment. By delineating exosome functions within the bone microenvironmental network and outlining corresponding biomaterial engineering strategies, this review offers a holistic perspective essential for advancing exosome-based therapies.

Acinar cell carcinoma (AcCC) has a certain risk of recurrence, metastasis or even death. This study aimed to explore the relationships between clinicopathological characteristics and survival in AcCC patients, and a nomogram model was developed and validated for predicting overall survival (OS). AcCC patients were identified from the Surveillance, Epidemiology, and End Results Program. An external validation was conducted using an independent cohort from our hospital. Independent prognostic factors for OS were determined using univariate/multivariate Cox regression analyses, and a nomogram was created to predict survival. The model was validated using various methods, including calibration curves, receiver operating characteristic curves, and concordance indexes. A total of 1306 patients (916 in the training set and 390 in the validation set) with AcCC were enrolled. The results of multivariate Cox regression analysis revealed that age, sex, advanced T stage, N stage, M stage, and the type of surgery were independent prognostic factors for OS. The established nomograms incorporating the clinical factors and surgery type had robust and accurate performance according to the concordance indexes (0.824) and area under the curve values of 0.864 and 0.829, respectively, in predicting 3-year survival and 5-year survival in the training set. Receiver operating characteristic curve also showed better prognostic prediction performance for OS in the internal and external validation group. Moreover, the calibration curves exhibited excellent agreement between the actual observations and nomogram predictions. The OS of high-risk patients exhibited worse than that of low-risk patients in Kaplan-Meier survival analysis. A nomogram based on clinical features and surgery was developed for the first time and validated to predict personalized 3- and 5-year OS in AcCC patients. It helps clinicians predict survival and obtain prognostic information. Integrating this nomogram into clinical practice could improve decision-making, optimize therapy, and enhance patient outcomes.

Articular cartilage repair remains challenging because of limited intrinsic regeneration and the need for sustained mechanical and biological support. We developed a silk fibroin (SF) scaffold combining directional freezing with HRP/H2O2-mediated enzymatic crosslinking. The resulting EF-SF hydrogel exhibited high compressive strength, limited swelling, aligned porosity, and delayed degradation. Kartogenin (KGN)-loaded PLGA nanoparticles were incorporated to form EF-SF/PK. Compared with direct KGN loading, PLGA encapsulation markedly reduced early release and prolonged KGN delivery. EF-SF/PK supported BMSC viability, proliferation, and chondrogenic gene expression, while LDH and residual peroxide measurements showed no progressive in vitro cytotoxicity. In a rabbit femoral cartilage-defect model, EF-SF/PK improved macroscopic, imaging, and histological repair over 12 weeks. These findings support a hierarchical SF scaffold that integrates mechanical stability with controlled local delivery for cartilage regeneration.

SIRT1 exerts pivotal roles in the pathogenesis of sepsis. However, the clinical relevance of SIRT1 genetic variants in the onset and progression of sepsis remains poorly understood. This multicenter hospital-based case–control study, for the first time, explored the potential genetic association of SIRT1 genetic variants with sepsis, as well as their impact on sepsis-associated inflammation. 785 septic patients and 776 controls from Han Chinese population were enrolled from four large Chinese general hospitals. SIRT1 rs12778366 T > C (785 cases, 776 controls) and rs4746720 T > C (765 cases, 774 controls) polymorphisms were successfully genotyped. No significant differences in the genotype/allele frequencies of SIRT1 polymorphisms between sepsis and control groups. The frequencies of rs4746720 TC/CC genotypes were significantly lower in patients with septic shock than those with sepsis subtype (OR = 0.685, 95

Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and are regarded as a promising approach for the treatment of cartilage defects. However, how to aggregate and adsorb BMSCs to the injured sites of cartilage and promote their directional differentiation into chondrocytes has always been a key issue to be solved. Here, we fabricated Kartogenin (KGN)-loaded PLGA nanobubbles (KGN-NBs) and swallowed them into BMSCs, obtaining KGN-NBs-containing BMSCs (KGN-NBs@BMSCs). Also, we designed a polylactic acid (PLA) acoustically response scaffold which can produce local sound field under low intensity ultrasound irradiation, and capture KGN-NBs@BMSCs to aggregate on the surface of scaffold. More importantly, KGN could be intracellularly released from KGN-NBs under a short burst of high-energy burst ultrasound irradiation, greatly promoting chondrogenic differentiation of BMSCs and favoring to repair articular cartilage defect. Our study provides a new strategy for the treatment of cartilage defects.

There are limited data regarding the impact of Hepatitis B virus (HBV) infection on the composition of human breast milk, and there is no international consensus on the nutritional management of newborns of HBV-positive mothers. We hypothesised that HBV infection can alter the composition of breast milk and that newborns require additional nutritional supplements for healthy growth. We conducted a prospective observational cohort study that recruited 150 pregnant women with HBV infection and matched them with a healthy control group. Multivariate linear regression analysis revealed that glucose and albumin concentrations were increased in the HBV group (av. 4.65 mmol/L and av. 5.66 g/L, respectively), whereas lactoferrin concentrations decreased (av. 537.68 pg/mL). Therefore, additional lactoferrin supplementation may be necessary for newborns delivered to women with HBV infection.

Evidence concerning the association between excessive total bile acid (TBA) concentrations and adverse perinatal outcomes in the recent Chinese guidelines for intrahepatic cholestasis of pregnancy (C-ICP), which recommend including asymptomatic hypercholanemia of pregnancy (AHP) in ICP management, is insufficient. This study aims to investigate the association between adverse perinatal outcomes and maternal TBA concentrations in patients with C-ICP and compare differences in adverse perinatal outcomes between AHP and ICP subgroups in different TBA concentrations. This retrospective cohort study included pregnant individuals with C-ICP (n = 957) who delivered and had regular antenatal examination records available at a hospital in Guangzhou, China, from January 2015 to December 2024. Participants were grouped according to TBA concentrations (low mild (LM), high mild (HM), severe (S), and extremely severe (ES)) and then sub-grouped into AHP and ICP subgroups within each TBA concentration group. Multivariate logistic regression models showed that the risk of adverse perinatal outcomes (including preterm birth, indicated preterm birth, meconium-stained amniotic fluid, and admission to the neonatology department) increased with TBA concentration. Compared to the LM group, the rate of adverse perinatal outcomes increased significantly from the S group onwards, reaching its highest rate in the ES group (preterm birth: P-trend < 0.001; indicated preterm birth: P-trend < 0.001; meconium-stained amniotic fluid: P-trend = 0.037; admission to the neonatology department: P-trend < 0.001; gestational age at delivery: P-trend < 0.001; birth weight of newborn: P-trend < 0.001). However, within the ES group, there was no significant difference in the risk of adverse perinatal outcomes between the AHP subgroup and the ICP subgroups. (preterm birth: odds ratio (OR) 0.41, 95

BACKGROUND:Accurate evaluation of the cartilage anatomy of the knee is helpful for clinical evaluation of the source of knee pain and the classification and treatment of knee osteoarthritis (OA). This study proposes a deep learning model for segmentation of knee articular cartilage in conventional proton density fat-saturated MRI sequences to assess cartilage morphology for subsequent injury grading. METHODS:This retrospective study was conducted at two radiology centers, involving 254 knees from 254 patients who had previously undergone MRI scans. The training-internal validation cohort included 219 knees from Center 1. The external validation cohort comprised 35 knees from Center 2. Two musculoskeletal radiology experts manually annotated the cartilage regions. A 3D Res U-net model was employed for segmentation, and its performance was compared with 3D U-net and 3D V-net models. Segmentation results were evaluated using the Dice coefficient and Jaccard index. RESULTS:The 3D Res U-net model demonstrated superior segmentation performance compared to the other deep learning methods. For cartilage in the lateral femorotibial joint, medial femorotibial joint, and patellofemoral joint, the average Dice coefficients with 3D Res U-net were 0.871, 0.860, and 0.858 in internal validation and 0.846, 0.837, and 0.819 in external validation, respectively. The Jaccard index followed a similar trend. CONCLUSION:The 3D Res U-net model improves knee cartilage segmentation in conventional MR imaging, contributing to the understanding of cartilage morphology and the improvement of clinically relevant decisions.

BACKGROUND:Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular event that triggers secondary brain injury in which microglial activation is central. This study explored how miR-92a-3p governs autophagy and inflammatory signaling in this context. METHODS:An in vitro ICH model was established using rat microglia exposed to hemoglobin, with lipopolysaccharide to induce autophagy. Cells were transfected with miR-92a-3p mimics or inhibitors. Apoptosis, miR-92a-3p/ATG14 expression, autophagy-related proteins (LC3, P62), and pro-inflammatory factors were assessed via molecular and cellular assays. RESULTS:Dual luciferase assays and ATG14 silencing confirmed direct targeting of ATG14 by miR-92a-3p. Upregulation of miR-92a-3p suppressed autophagy and thereby reduced inflammatory cytokine release, whereas inhibition of miR-92a-3p restored autophagic activity and reduced inflammation. CONCLUSION:These findings establish miR-92a-3p as a critical regulator of microglial autophagy and inflammation after hemorrhagic stroke and identify it as a prospective therapeutic target for neuroinflammatory modulation.

Context Internet hospitals have emerged as a digital innovation in healthcare, optimizing resource allocation and enhancing patient experience. They also support hierarchical diagnosis and treatment and contribute to the Healthy China initiative. Objectives To establish a comprehensive evaluation system to promote the sustainable development of Internet hospitals. Methods A systematic review of literature related to the evaluation of Internet-based healthcare services was conducted. Using Web of Science and CNKI as data sources, studies published between 2015 and 2024 were screened based on predefined criteria, focusing on high-quality journals and research reports. The selected literature was coded and analyzed across four dimensions: patient services, doctor services, management services, and information security. Results The final analysis included 34 papers, with 25 mentioning patient services indicators, 20 mentioning doctor services indicators, 18 mentioning medical services process management indicators, and 9 mentioning information security. This study identifies key evaluation indicators and examines their interrelationships, highlighting potential systemic risks from localized optimizations. Conclusion This review analyzed Internet hospital evaluation across patient services, doctor services, services management, and information security. While it highlights potential efficiency gains, it notes the lack of comprehensive indicators, limiting assessment and improvement. For sustainable development, a more comprehensive evaluation system should integrate multi-stakeholder perspectives (patients, doctors, institutions), address systemic risks from localized optimization, and incorporate coordinated policy considerations.

Objectives: Traditional antifungal drug treatment (AT) often induce resistance that may limit their ability to eradicate oral candidiasis. This study aimed to evaluate the efficacy of photodynamic therapy (PDT) compared to AT in reducing Candida colony count or improving clinical outcomes in oral candidiasis. Methods: We searched relevant articles through Cochrane Library, Web of Science, and PubMed databases up to June 25, 2024. Randomized controlled trials (RCTs) or other clinical comparative studies assessing the effectiveness of single or adjunctive PDT, or conventional chemical therapies were included. Study outcomes were clinical response or the changes from baseline in Candida colony counts. Results: A total of 16 clinical trials, including 13 RCTs, were enrolled. The pooled results showed PDT and AT therapy for oral candidiasis have comparable efficacy in the overall response rate (RR=0.97, P = 0.540) and no significant difference in the complete response rate between them. PDT+AT had a higher curing rate than AT alone (RR=1.67, CI: 1.16–2.39, P = 0.005). The network meta‑analysis revealed that PDT+AT, PDT or AT alone improved the reduction of Candida colony counts compared to distilled water treatment. Moreover, PDT+AT was significantly more effective than either PDT or AT alone, and it was most likely to provide the greatest benefit in Candida clearance, followed by AT, PDT, chlorhexidine, and distilled water. There was no statistical difference in the improvement of Candida colony counts between the PDT and AT groups. Conclusions: PDT demonstrates comparable efficacy to AT in treating oral candidiasis and may serve as a promising alternative approach. Combining PDT with AT further improves cure rates and Candida reduction. Future large-scale, high-quality RCTs are warranted to confirm these findings.

: The kidneys play an irreplaceable role in metabolism and excretion. However, Acute Kidney Injury (AKI) often occurs due to high local concentrations of drugs, inflammation, and trauma. Activated optical probes with excellent detection performance can effectively identify biomarkers in the initial stage of AKI and play an important role in evaluating AKI and preventing the development of diseases. This article summarizes representative design strategies for molecular probes and special diagnostic applications. These molecular probes show great potential in basic research and clinical diagnosis, enabling enhanced images of tissue structure and biomarkers, as well as early diagnosis of AKI. In addition, the difficulties and challenges that optical probes may face in the development and application of AKI are also discussed in this article.

Excessive inflammatory responses in sepsis result in multiorgan dysfunction, with the majority of these responses being modulated by the activity of a disintegrin and metalloproteinase 10 (ADAM10). Due to the widespread distribution of ADAM10 and its numerous substrates, therapies targeting ADAM10 will have a range of physiological effects, including modulating inflammation, but may also cause toxic side effects. Precise therapeutic targets for regulating ADAM10 in specific diseases are needed. In several studies, tetraspanin family members have been identified as regulators of specific proteins, including ADAM10. In various cell types, the identical tetraspanin exhibits distinct effects on the regulation of ADAM10, indicating that tetraspanins possess cell-specific roles in modulating ADAM10. Furthermore, the interaction of diverse tetraspanins with ADAM10 results in the cleavage of various substrates. In this review, we provide a summary of the diverse tetraspanins that are currently recognized to interact with ADAM10 to identify potential new targets for regulating ADAM10 in sepsis.

PURPOSE:To study the potential advantages of phosphorus magnetic resonance spectroscopy (31P-MRS) in differentiating advanced from mild fibrosis in non-alcoholic fatty liver disease (NAFLD) and early diagnosis at high field strength MR (9.4 Tesla). METHODS:Fibrosis of normal and carbon tetrachloride (CCl4)-treated male rats was staged into: none (F0), perisinusoidal or periportal (F1), perisinusoidal and portal/periportal (F2), bridging fibrosis (F3) and cirrhosis (F4) by Sirius Red staining. The degree of steatosis and inflammatory activity were also graded based on Hematoxylin and Eosin staining. Rats were divided into different groups by different stages of fibrosis (F0, F1-2, F3-4) and laboratory blood tests were performed to verify the degree of liver injury. 31P-MRS was performed at 9.4T MR to obtain signal peaks of different phosphorus metabolites and the changes of the ratios between the peaks were observed. RESULTS:At 9.4 T, phosphoethanolamine (PE), phosphocholine (PC) and glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC) could be separated respectively from the peaks of phosphomonoesters (PME) and phosphodiesters (PDE), meanwhile nicotinamide adenine dinucleotide phosphate (NADPH) and uridine diphosphate glucose (UDPG) showed up as well. The marker of cell membrane metabolism, in F1-2, PME/PDE (P < 0.001), PC/GPE (P < 0.01), PC/GPC (P < 0.05) and PC/(PME + PDE) (P < 0.05) decreased while GPE/(PME + PDE) (P < 0.05) and GPC/(PME + PDE) (P < 0.05) increased significantly. In F3-4, there was a recovery trend of most ratios, especially for PC/(PME + PDE) (P < 0.05). As for the main ratio related to energy metabolism, β-ATP/Ptotal (P < 0.05) decreased in the early stage of the disease (F1-2) and this decline was maintained in advanced stage (F3-4). NADPH/Ptotal (P < 0.01) and β-ATP/Pi (inorganic phosphate) (P < 0.05) ratio was lower in F3-4 comparing with F0. CONCLUSION:31P-MRS can generally stage the liver fibrosis by comparing the ratios of the phosphorus metabolites resonance peaks at 9.4 T and more importantly it can be used for early diagnosis.

ObjectiveAccurate preoperative evaluation of rectal cancer lung metastases (RCLM) is critical for implementing precise medicine. While artificial intelligence (AI) methods have been successful in detecting liver and lymph node metastases using magnetic resonance (MR) images, research on lung metastases is still limited. Utilizing MR images to classify RCLM could potentially reduce ionizing radiation exposure and the costs associated with chest CT in patients without metastases. This study aims to develop and validate a transformer-based deep learning (DL) model based on pelvic MR images, integrated with clinical features, to predict RCLM.MethodsA total of 819 patients with histologically confirmed rectal cancer who underwent preoperative pelvis MRI and carcinoembryonic antigen (CEA) tests were enrolled. Six state-of-the-art DL methods (Resnet18, EfficientNetb0, MobileNet, ShuffleNet, DenseNet, and our transformer-based model) were trained and tested on T2WI and DWI to predict RCLM. The predictive performance was assessed using the receiver operating characteristic (ROC) curve.ResultsOur transformer-based DL model achieved impressive results in the independent test set, with an AUC of 83.74% (95% CI, 72.60%-92.83%), a sensitivity of 80.00%, a specificity of 78.79%, and an accuracy of 79.01%. Specifically, for stage T4 and N2 rectal cancer cases, the model achieved AUCs of 96.67% (95% CI, 87.14%-100%, 93.33% sensitivity, 89.04% specificity, 94.74% accuracy), and 96.83% (95% CI, 88.67%-100%, 100% sensitivity, 83.33% specificity, 88.00% accuracy) respectively, in predicting RCLM. Our DL model showed a better predictive performance than other state-of-the-art DL methods.ConclusionThe superior performance demonstrates the potential of our work for predicting RCLM, suggesting its potential assistance in personalized treatment and follow-up plans.

This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28

ObjectiveFor elective cesarean section patients with gestational diabetes mellitus (GDM), there is a lack of evidence-based research on the use of enhanced recovery after surgery (ERAS). This study aims to compare the ERAS after-surgery protocol and traditional perioperative management.Research design and methodsIn this retrospective cohort study, singleton pregnancies with good glucose control GDM, delivered by elective cesarean sections under intravertebral anesthesia at least 37 weeks from January 1 to December 31, 2022, were collected at the Third Affiliated Hospital of Sun Yat-sen University. We divided all enrolled pregnant women and newborns into an ERAS group and a control group (the traditional perioperative management group) based on their adherence to the ERAS protocol. The primary outcome was the preoperative blood glucose level, with an increase of more than 1 mmol/L indicating clinical significance when compared to the control group. The secondary outcome was centered around an adverse composite outcome that affected both mothers and newborns.ResultsWe collected a total of 161 cases, with 82 in the ERAS group and 79 in the control group. Although the mean preoperative blood glucose level in the ERAS group was significantly higher than in the control group (5.01 ± 1.06 mmol/L vs. 4.45 ± 0.90 mmol/L, p<0.001), the primary outcome revealed that the mean glycemic difference between the groups was 0.47 mmol/L (95% CI 0.15-0.80 mmol/L), which was below the clinically significant difference of 1 mmol/L. For the secondary outcomes, the ERAS group had an 86% lower risk of a composite adverse outcome compared to the control group. This included a 73% lower risk of perioperative maternal hypoglycemia and a 92% lower rate of neonatal hypoglycemia, all adjusted by age, hypertensive disorder of pregnancy, BMI, gestational weeks, primigravidae, primary pregnancy, GDM, surgery duration, and fasting glucose.ConclusionImplementing a low-dose carbohydrate ERAS in pregnant women with GDM prior to elective cesarean section, compared to traditional perioperative management, does not lead to clinically significant maternal glucose increases and thus glucose-related maternal or neonatal perioperative complications.

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis. Immunotherapy has shown great potential in the treatment of osteosarcoma. However, the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment. The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment. Here, we prepared a dual pH-sensitive nanocarrier, loaded with the photosensitizer Chlorin e6 (Ce6) and CD47 monoclonal antibodies (aCD47), to deliver synergistic photodynamic and immunotherapy of osteosarcoma. On laser irradiation, Ce6 can generate reactive oxygen species (ROS) to kill cancer cells directly and induces immunogenic tumor cell death (ICD), which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47. Moreover, both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages, promote antigen presentation, and eventually induce T lymphocyte-mediated antitumor immunity. Overall, the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma, which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Background: Current studies have demonstrated that disintegrin and metalloproteinase 17 (ADAM17) plays a critical role in the pathogenesis of sepsis. MicroRNA (miR)-145 is known to control immune responses as an anti-inflammatory modulatory molecule. However, a fundamental understanding of how miR-145 regulates ADAM17 and, more broadly, sepsis-induced inflammatory response remains unknown. Methods: We used western blotting and quantitative real-time PCR (qRT-PCR) to measure expression levels of ADAM17 and miR-145. Enzyme-linked immunosorbent assays (ELISA) were performed to measure cytokine production. To determine if ADAM17 is a target gene of miR-145, bioinformatics analyses and luciferase reporter assays were conducted. The impacts of ADAM17 and miR-145 on sepsis-induced inflammatory responses were accessed in vitro using human umbilical endothelial cells (HUVECs) treated with lipopolysaccharide (LPS). Sepsis-induced inflammatory response was measured in vivo using a polymicrobial septic mouse model induced by cecal ligation and puncture (CLP) with pre-injection of a miR-145 agomir. Results: In HUVECs treated with LPS, miR-145 expression was downregulated and miR-145 negatively regulated ADAM17 expression through direct binding to the ADAM17 transcript 3′-UTR. MiR-145 overexpression markedly reduced LPS-induced inflammatory cytokine production by targeting ADAM17 in HUVECs. In comparison to CLP-induced septic mice treated with a control agomir, treatment with a miR-145 agomir significantly reduced the expression of ADAM17, numerous downstream cytokines such as IL-6, TNF-α, IL-1β and MCP-1, and the endothelial injury factors ICAM-1, VCAM-1. The miR-145 agomir also alleviated acute lung and kidney injury and improved the survival rate of septic mice. Conclusions: This study showed that miR-145, by specifically targeting ADAM17, negatively regulates sepsis-induced inflammatory responses and vascular endothelial injury, and ultimately improved organ injury and survival during sepsis. The underlying mechanism for the regulation of ADAM17 expression by miR-145 and sepsis-induced inflammatory reactions may offer sepsis patients a novel therapeutic option.

BACKGROUND:Ultraviolet (UV) damage is closely related to skin photoaging and many skin diseases, including dermatic tumors. N6-methyladenosine (m6A) modification is an important epigenetic regulatory mechanism. However, the role of m6A methylation in apoptosis induced by repeated UV irradiation has not been characterized.OBJECTIVE:To explore m6A methylation changes and regulatory mechanisms in the repeated UV-induced skin damage process, especially apoptosis.METHODS:HaCaT cells and BALB/c-Nu nude mice were exposed to repeated UVB/UVA+UVB irradiation. Colorimetry and flow cytometry were used to measure cellular viability and apoptosis. m6A-modified genes were detected via colorimetry and methylated RNA immunoprecipitation (MeRIP) sequencing. Methyltransferases and demethylases were detected via RT-PCR, western blotting and immunohistochemistry. Transfection of siRNA and plasmid was performed to knock down or overexpress the selected genes.RESULTS:After UVB irradiation, 861 m6A peaks were increased and 425 m6A peaks were decreased in HaCaT cells. The differentially modified genes were enriched in apoptosis-related pathways. The m6A demethylase FTO was decreased in both HaCaT cells and mouse skin after UV damage. Overexpressing FTO could improve cell viability, inhibit apoptosis and decrease RNA-m6A methylation, including LPCAT3-m6A, which increase LPCAT3 expression, cell viability promotion and apoptosis inhibition.CONCLUSION:Our study identified the cell m6A methylation change lists after repeated UVB irradiation, and revealed that FTO and LPCAT3 play key roles in the m6A methylation pathogenesis of UV-induced skin cell apoptosis. FTO-m6A-LPCAT3 might serve as a novel upstream target for preventing and treating photoaging and UV-induced skin diseases.