ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

Objective To evaluate the feasibility of intravesical instillation of urokinase and heparin sodium in the treatment of bladder clot irrigation.Methods This report discusses the diagnosis and treatment of three patients with bladder blood clot tamponade confirmed by abdominal and pelvic computed tomography(CT)scans enrolled from our hospital during Jun. to Sep. 2024, and discuss the relevant literature.Results A solution containing urokinase(20 000 IU)and heparin sodium(125 000 U)was instilled through a three-way catheter and retained for 30 minutes before drainage. Complete clot dissolution was achieved in all cases, with immediate relief of hypogastric distension and pain. Post-procedural CT showed restored bladder lumen patency. Hemoglobin levels decreased by 2-5 g/L without complications.Conclusion This preliminary trial demonstrated that intravesical instillation of urokinase-heparin provides a safe and effective minimally invasive alternative for bladder clot in irrigation cases.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

ObjectiveTo investigate the urate-lowering effect of Shenling Qushi prescription in the mouse model of hyperuricaemia. MethodsSixty-three C57BL/6N mice were randomly assigned to the following groups （n=9）： Control， model， low-dose （6 g·kg^-1） Shenling Qushi prescription， medium-dose （12 g·kg^-1） Shenling Qushi prescription， high-dose （24 g·kg^-1） Shenling Qushi prescription， medium-dose Shenling Qushi prescription plus febuxostat （12+0.003 g·kg^-1）， and febuxostat （3 mg·kg^-1）. A mouse model of persistent hyperuricaemia was established via intraperitoneal injection of potassium oxazolamide （250 mg·kg^-1） combined with oral administration of allopurinol （300 mg·kg^-1） over a 28-day period. Concurrently， the prescription was administered orally at the specified doses once daily for 21 consecutive days. Throughout the experiment， mouse body weight， food intake， water consumption， and urine output were measured and recorded. Kidney and liver indices were calculated. Renal histopathological changes were observed by haematoxylin and eosin staining. Serum uric acid （SUA） and urinary uric acid （UUA） levels， along with xanthine oxidase （XOD） and adenosine deaminase （ADA）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities， were determined. Real-time PCR was employed to assess the mRNA levels of urate anion transporter 1 （URAT1） and glucose transporter 9 （GLUT9） in the renal tissue， alongside those of XOD and ADA in the liver tissue. The protein levels of URAT1 and GLUT9 in the renal tissue were determined by Western blot. ResultsCompared with the normal group， model mice exhibited reduced food intake and body weight （P<0.01）， decreased water consumption yet increased urine output， no significant change in the liver index but increased kidney index （P<0.01）. Pathological findings revealed renal tissue damage including glomerular atrophy， epithelial cell detachment， and inflammatory cell infiltration. Furthermore， the model group exhibited elevated UUA and SUA levels （P<0.01）， enhanced activities of ALT， AST， XOD， and ADA in the liver tissue （P<0.05， P<0.01）， upregulated mRNA and protein levels of URAT1 and GLUT9 in the renal tissue （P<0.05）， alongside markedly elevated mRNA levels of XOD and ADA in the liver （P<0.01）. Compared with the model group， the Shenling Qushi prescription groups showed no significant changes in body weight or food intake， with water consumption and urine output remaining within normal ranges， alleviated glomerular atrophy， with reduced pathological damage such as inflammatory infiltration， declined UUA and SUA levels （P<0.01）， and increased activities of ALT， AST， XOD， and ADA in the serum （P<0.01）. Real-time PCR results demonstrated that Shenling Qushi prescription downregulated the mRNA levels of URAT1 and GLUT9 in the renal tissue （P<0.05， P<0.01） and XOD and ADA in the hepatic tissue （P<0.05， P<0.01）. Western blot results demonstrated Shenling Qushi prescription reduced the protein levels of URAT1 and GLUT9 （P<0.05， P<0.01）. ConclusionShenling Qushi prescription modulates fluid balance and reduces uric acid levels， thereby alleviating renal injury in hyperuricaemic mice. This effect is highly likely mediated through inhibition of uric acid synthesis and reabsorption.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.