Exotic plantations differ in "nursing" an understory invader: A probe into invasional meltdown.

Forest plantations most likely promote exotic plant invasion. Using an in situ monitoring method, this study investigated the traits correlated with growth and reproduction of an understory invader, Phytolacca americana L., and ecological factors including understory irradiance, soil stoichiometry and microbial patterns associated with these traits in different exotic plantations of Robinia pseudoacacia L. and Pinus thunbergii Parl. at Mount Lao, Qingdao, China. We found that the traits of P. americana underneath the R. pseudoacacia stand might be situated at the fast side of the trait economic spectrum. The R. pseudoacacia stand appeared to "nurse" P. americana. Furthermore, we intended to explain the nurse effects of R. pseudoacacia stands by examining their ecological factors. First, the R. pseudoacacia stand created understory light attenuation, which matched the sciophilous feature of P. americana. Second, the soil beneath the R. pseudoacacia stand might benefit P. americana more since the soil has greater resource availability. Third, a higher microbial diversity was found in the soil derived from P. americana underneath the R. pseudoacacia stand. A greater abundance of plant pathogens was detected in the soil derived from P. americana in the R. pseudoacacia stand, while more abundant mycorrhizal fungi were detected in the P. thunbergii stand. We speculate that plant pathogens can defend P. americana from aggression from other understory competitors. The mycorrhizal fungi in the P. thunbergii stand might benefit P. americana while simultaneously benefiting other understory plants. Intensive competition from other plants might interfere with P. americana. The potential relationships between plant performance and ecological factors may explain the invasion mechanism of P. americana. The present study provides a novel insight on the facilitative effects of exotic tree plantation on an exotic herb through the modification of soil biota, with implications for the biocontrol of invasive species and forest management and conservation.

Programable Albumin-Hitchhiking Nanobodies Enhance the Delivery of STING Agonists to Potentiate Cancer Immunotherapy.

Stimulator of interferon genes (STING) is a promising target for potentiating antitumor immunity, but multiple pharmacological barriers limit the clinical utility, efficacy, and/or safety of STING agonists. Here we describe a modular platform for systemic administration of STING agonists based on nanobodies engineered for in situ hitchhiking of agonist cargo on serum albumin. Using site-selective bioconjugation chemistries to produce molecularly defined products, we found that covalent conjugation of a STING agonist to anti-albumin nanobodies improved pharmacokinetics and increased cargo accumulation in tumor tissue, stimulating innate immune programs that increased the infiltration of activated natural killer cells and T cells, which potently inhibited tumor growth in multiple mouse tumor models. We also demonstrated the programmability of the platform through the recombinant integration of a second nanobody domain that targeted programmed cell death ligand-1 (PD-L1), which further increased cargo delivery to tumor sites while also blocking immunosuppressive PD-1/PD-L1 interactions. This bivalent nanobody carrier for covalently conjugated STING agonists stimulated robust antigen-specific T cell responses and long-lasting immunological memory, conferred enhanced therapeutic efficacy, and was effective as a neoadjuvant treatment for improving responses to adoptive T cell transfer therapy. Albumin-hitchhiking nanobodies thus offer an enabling, multimodal, and programmable platform for systemic delivery of STING agonists with potential to augment responses to multiple immunotherapeutic modalities.

Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production.

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation. In this study, we observed significant upregulation of TrxR1 specifically in non-small cell lung cancer (NSCLC), rather than small cell lung cancer. Moreover, TrxR1 expression exhibited associations with survival rate, tumor volume, and histological classification. We developed a novel TrxR1 inhibitor named LW-216 and assessed its antitumor efficacy in NSCLC. Our results revealed that LW-216 is effectively bound with intracellular TrxR1 at sites R371 and G442, facilitating TrxR1 ubiquitination and suppressing TrxR1 expression, while not affecting TrxR2 expression. Treatment of LW-216-induced DNA damage and cell apoptosis in NSCLC cells through the generation of reactive oxygen species (ROS). Importantly, supplementation with N-acetylcysteine (NAC) or ectopic TrxR1 expression reversed LW-216-induced apoptosis. Furthermore, LW-216 displayed potent tumor growth inhibition in NSCLC cell-implanted mice, reducing TrxR1 expression in xenografts. Remarkably, LW-216 exhibited superior antitumor activity compared to Auranofin in vivo. Collectively, our research provides compelling evidence supporting the potential of targeting TrxR1 by LW-216 as a promising therapeutic strategy for NSCLC.

Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function.

The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

Nanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy.

Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving the response to immune checkpoint inhibitors (ICIs). However, the potency and clinical efficacy of 5'-triphosphate RNA (3pRNA) agonists of RIG-I are hindered by multiple pharmacological barriers, including poor pharmacokinetics, nuclease degradation, and inefficient delivery to the cytosol where RIG-I is localized. Here, we address these challenges through the design and evaluation of ionizable lipid nanoparticles (LNPs) for the delivery of 3p-modified stem-loop RNAs (SLRs). Packaging of SLRs into LNPs (SLR-LNPs) yielded surface charge-neutral nanoparticles with a size of ∼100 nm that activated RIG-I signaling in vitro and in vivo. SLR-LNPs were safely administered to mice via both intratumoral and intravenous routes, resulting in RIG-I activation in the tumor microenvironment (TME) and the inhibition of tumor growth in mouse models of poorly immunogenic melanoma and breast cancer. Significantly, we found that systemic administration of SLR-LNPs reprogrammed the breast TME to enhance the infiltration of CD8+ and CD4+ T cells with antitumor function, resulting in enhanced response to αPD-1 ICI in an orthotopic EO771 model of triple-negative breast cancer. Therapeutic efficacy was further demonstrated in a metastatic B16.F10 melanoma model, with systemically administered SLR-LNPs significantly reducing lung metastatic burden compared to combined αPD-1 + αCTLA-4 ICI. Collectively, these studies have established SLR-LNPs as a translationally promising immunotherapeutic nanomedicine for potent and selective activation of RIG-I with the potential to enhance response to ICIs and other immunotherapeutic modalities.

Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers.

INTRODUCTION: Previous studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers. OBJECTIVES: To assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites. METHODS: A total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975-2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs). RESULTS: In patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]-19·85[95 %CI, 16·69-23·44]; AER 5·77-210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]-19·25[95 %CI, 15·76-23·29]; AER 4·36-159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]-24·71[95 %CI, 16·28-35·96]; AER 1·01-37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group. CONCLUSION: The CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.

[Progress in surgical treatment of osteochondral lesion of talus].

Objective: To provide a comprehensive overview of the surgical treatments of osteochondral lesion of talus (OLT) and offer valuable insights for clinical practice. Methods: The advantages and limitations of surgical treatments for OLT were comprehensively summarized through an extensive review of domestic and abroad relevant literature in recent years. Results: Currently, there exist numerous surgical treatments for the OLT, all of which can yield favorable outcomes. However, each method possesses its own set of merits and demerits. The short-term effectiveness of bone marrow stimulation in treating primary OLT with a diameter less than 15 mm is evident, but its long-term effectiveness diminishes over time. Autologous osteochondral transplantation (AOT) and osteochondral allograft transplantation (OAT) are suitable for OLT with large defects and subchondral bone cysts. However, incomplete anatomical matching between the donor and recipient bones may results in the formation of new subchondral bone cysts, while AOT also presents potential complications at the donor site. In contrast to AOT and OAT, particulated juvenile cartilage allograft transplantation obviates the need for additional osteotomy. Furthermore, juvenile cartilage exhibits enhanced potential in delivering active chondrocytes to the site of cartilage defect, surpassing that of adult cartilage in tissue repair efficacy. Cell transplantation has demonstrated satisfactory effectiveness; however, it is associated with challenges such as the requirement for secondary surgery and high costs. Autologous matrix-induced chondrogenesis technology has shown promising effectiveness in the treatment of primary and non-primary OLT and OLT with large defect and subchondral bone cysts. However, there is a scarcity of relevant studies, most of which exhibit low quality. Adjuvant therapy utilizing biological agents represents a novel approach to treating OLT; nevertheless, due to insufficient support from high-quality studies, it has not exhibited significant advantages over traditional treatment methods. Furthermore, its long-term effectiveness remain unclear. Conclusion: The optimal choice of surgical treatment for OLT is contingent not only upon the characteristics such as nature, size, and shape but also takes into consideration factors like advancements in medical technology, patient acceptance, economic status, and other pertinent aspects to deliver personalized treatment.

Prognostic impacts of repeated sepsis in intensive care unit on autoimmune disease patients: a retrospective cohort study.

BACKGROUND: Autoimmune diseases (ADs) may be complicated by sepsis when intensive care unit (ICU) admission. But repeated sepsis among AD patients has not been studied yet. The aim of this study is to investigate the impact of repeated in-ICU sepsis on the 1-year overall-cause mortality, septic shock and in-ICU death of AD patients. METHODS: Data of AD patients with sepsis retrieved from Medical Information Mart for Intensive Care IV (MIMIC-IV) database were divided into the single group and the repeated group according to the frequency of in-ICU sepsis. Propensity score matching was used to balance inter-group bias. Cox proportional hazard regression and sensitivity analysis were utilized to assess the variables on mortality. RESULTS: The incidence of repeated in-ICU sepsis in baseline was 19.8%. The repeated in-ICU sepsis was a risk factor for 1-year overall-cause mortality among AD patients (adjusted hazard ratio [HR] = 1.50, 95% CI: 1.16-1.93, P = 0.002), with robust adjusted HRs by the adjustment for confounders in the sensitivity analysis (all P < 0.01). Maximum Sequential Organ Failure Assessment (Max SOFA), Charlson comorbidity index (CCI) and Simplified Acute Physiology Score-II (SAPS-II) were risk factors for 1-year overall-cause mortality among AD with repeated sepsis (Max SOFA: HR = 1.09, P = 0.002; CCI: HR = 1.08, P = 0.039; SAPS-II: HR = 1.03, P < 0.001). CONCLUSIONS: Compared to single hit, repeated in-ICU sepsis was independently related to a higher risk of 1-year overall-cause mortality among AD patients. Assessment tools (Higher SOFA, CCI and SAPS-II scores) were closely linked to poor prognosis of AD with repeated sepsis and helped to reflect ill physical conditions for the patients.

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH can be triggered by the intravenously injected DFO, resulting in the release, reactivation, and deep penetration of encapsulated HAase inside tumors. Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Overall, this work presents a proof-of-concept of the dynamic disassembly of metal-polyphenol nanoparticles for extracellular drug delivery as well as the modulation of TECM and immunosuppressive tumor microenvironment.

TMSOTf-Promoted Cyclization of Indole-2-methyl-α-aminoketones: Access to 4-Aryl-Substituted ß-Carbolines.

An efficient method to construct 4-aryl-substituted ß-carbolines from indole-2-methyl-α-aminoketones via a TMSOTf-promoted annulation reaction was reported. High yield along with wide substrate scope and functional group tolerance make this reaction applicable to build various highly potential bioactive ß-carboline derivatives.

A More Efficient Method for Preparing a MIP-CQDs/ZnO1-x Photodegradant with Highly Selective Adsorption and Photocatalytic Properties.

The application of semiconductor photocatalysts in wastewater treatment always has a drawback, which is the lack of selectivity for pollutants, but molecular imprinting technology (MIT) is a remarkable method for preparing highly selective adsorbents for low concentration target pollutants. Up to now, the research of molecular imprinting materials has mainly focused on organic polymers, and there has been little research on inorganic molecular imprinting materials. In the present work, we introduced carbon quantum dots (CQDs) into the flower-like hierarchical ZnO to prepare photocatalysts CQDs/ZnO. Further, with ciprofloxacin (CIP) as the template molecule, a molecular imprinting material MIP-CQDs/ZnO1-x was prepared by introducing both oxygen vacancies and imprinted cavities into CQDs/ZnO by the hydrothermal calcination method. It can not only increase the concentration of oxygen vacancies and broaden the light absorption range of zinc oxide without changing the crystal form of ZnO but also make it have the characteristics of preferential adsorption and degradation of CIP during the degradation process. Under the synergistic effect of CQDs, oxygen vacancies, and molecularly imprinted cavities, the molecularly imprinted material exhibits excellent photocatalytic and selective adsorption performance.

Cascade hydroarylation/Diels-Alder cycloaddition of alkynylindoles with electron-deficient alkynes and alkenes.

Herein, a novel cascade gold(I)-catalyzed hydroarylation of alkynylindoles and subsequent Diels-Alder cycloaddition with electron-deficient alkynes and alkenes is described. A variety of azepino-fused hydrocarbazoles and carbazoles were obtained in moderate to excellent yields. Key features of this methodology are low catalyst loadings, high regioselectivity, broad functional group tolerances, access to important heterocycles, and 100% atom economy.

Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the ubiquitin E3 ligase ßTRCP in the form of molecular glue. C1 significantly inhibits the proliferation and metastasis of TNBC cells both in vitro and in vivo and in TNBC patient-derived organoids, and these antitumor effects are attributed to the degradation of eEF2K by C1. Additionally, combination treatment of C1 with paclitaxel, a commonly used chemotherapeutic drug, exhibits synergistic anti-tumor effects against TNBC. This study not only generates a powerful research tool to investigate the therapeutic potential of targeting eEF2K, but also provides a promising lead compound for developing novel drugs for the treatment of TNBC and other cancers.

Targeting Lysosome for Enhanced Cancer Photodynamic/Photothermal Therapy in a "One Stone Two Birds" Pattern.

Highly immunogenic programmed death of tumor cells, such as immunogenic cell death (ICD) and pyroptosis, strengthens antitumor responses and thus represents a promising target for cancer immunotherapy. However, the development of ICD and pyroptosis inducers remains challenging, and their efficiency is typically compromised by self-protective autophagy. Here, we report a potent ICD and pyroptosis-inducing strategy by coupling combined photodynamic/photothermal therapy (PTT/PDT) to biological processes in cancer cells. For this purpose, we rationally synthesize a lysosomal-targeting boron-dipyrromethene dimer (BDPd) with intense NIR absorption/emission, high reactive oxygen species (ROS) yield, and photothermal abilities, which can be self-assembled with Pluronic F127, producing lysosomal-acting nanomicelles (BDPd NPs) to facilitate cancer cell internalization of BDPd and generation of intracellular ROS. Owing to the favorable lysosomal-targeting ability of the morpholine group on BDPd, the intracellular BDPd NPs can accumulate in the lysosome and induce robust lysosomal damage in cancer cells upon 660 nm laser irradiation, which results in the synergetic induction of pyroptosis and ICD via activating NLRP3/GSDMD and caspase-3/GSDME pathways simultaneously. More importantly, PTT/PDT-induced self-protective autophagic degradation was blocked due to the dysfunction of lysosomes. Either intratumorally or intravenously, the injected BDPd NPs could markedly inhibit the growth of established tumor tissues upon laser activation, provoke local and systemic antitumor immune responses, and prolong the survival time in the mouse triple-negative breast cancer model. Collectively, this work represents a promising strategy to boost the therapeutic potential of PTT/PDT by coupling phototherapeutic reagents with the subcellular organelles, creating a "one stone two birds" pattern.

Iron-Mediated Reductive Amidation of Triazine Esters with Nitroarenes.

A reductive amidation of triazine esters with nitroarenes by using cheap iron as a reducing metal in the presence of TMSCl in DMF was developed. The reactions proceeded efficiently under transition metal-free conditions to give the corresponding amides in moderate to good yields with good functional group compatibility. Preliminary mechanistic investigations indicated that nitrosobenzene, N-phenyl hydroxylamine, azoxybenzene, azobenzene, aniline, and N-arylformamide possibly served as the intermediates of the reaction.

Control of CD4+ T cells to restrain inflammatory diseases via eukaryotic elongation factor 2 kinase.

CD4+ T cells, particularly IL-17-secreting helper CD4+ T cells, play a central role in the inflammatory processes underlying autoimmune disorders. Eukaryotic Elongation Factor 2 Kinase (eEF2K) is pivotal in CD8+ T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension. However, its specific immunological role in CD4+ T cell activities and related inflammatory diseases remains elusive. Our investigation has uncovered that the deficiency of eEF2K disrupts the survival and proliferation of CD4+ T cells, impairs their ability to secrete cytokines. Notably, this dysregulation leads to heightened production of pro-inflammatory cytokine IL-17, fosters a pro-inflammatory microenvironment in the absence of eEF2K in CD4+ T cells. Furthermore, the absence of eEF2K in CD4+ T cells is linked to increased metabolic activity and mitochondrial bioenergetics. We have shown that eEF2K regulates mitochondrial function and CD4+ T cell activity through the upregulation of the transcription factor, signal transducer and activator of transcription 3 (STAT3). Crucially, the deficiency of eEF2K exacerbates the severity of inflammation-related diseases, including rheumatoid arthritis, multiple sclerosis, and ulcerative colitis. Strikingly, the use of C188-9, a small molecule targeting STAT3, mitigates colitis in a murine immunodeficiency model receiving eEF2K knockout (KO) CD4+ T cells. These findings emphasize the pivotal role of eEF2K in controlling the function and metabolism of CD4+ T cells and its indispensable involvement in inflammation-related diseases. Manipulating eEF2K represents a promising avenue for novel therapeutic approaches in the treatment of inflammation-related disorders.

[Reflections on the Implications of the Developments in ChatGPT for Changes in Medical Education Models].

Ever since its official launch, Chat Generative Pre-Trained Transformer, or ChatGPT, a natural language processing tool driven by artificial intelligence (AI) technology, has attracted much attention from the education community. ChatGPT can play an important role in the field of medical education, with its potential applications ranging from assisting teachers in designing individualized teaching scenarios to enhancing students' practical ability for solving clinical problems and improving teaching and research efficiency. With the developments in technology, it is inevitable that ChatGPT, or other generative AI models, will be thoroughly integrated in more and more medical contexts, which will further enhance the efficiency and quality of medical services and allow doctors to spend more time interacting with patients and implement personalized health management. Herein, we suggested that proactive reflections be made to figure out the best way to cultivate health professional in the context of New Medical Education, to help more medical professionals enhance their understanding of developments in artificial intelligence, and to make preparations for the challenges that will emerge in the new round of technological revolution. Medical educators should focus on guiding students to make proper use of AI tools in the appropriate context, thereby prevening abuse or overreliance caused by a lack of discrimating ability. Teachers should focus on helping medical students make improvements in clinical reasoning skills, self-directed learning, and clinical practical skills. Teachers should stress the importance for medical students to understand the philosophical implications of the mind-body unity concept, holistic medical thinking, and systematic medical thinking. It is important to enhance medical students' humanistic qualities, cultivate their empathy and communication skills, and continually enhance their ability to meet the requirements of individualized precision diagnosis and treatment so that they will better adapt to the future developments in medicine.

Rhodium(III)-catalyzed intermolecular [3+3] annulation of benzoxazines with quinone compounds: access to spiro-heterocyclic scaffolds.

A rhodium(III)-catalyzed redox-neutral spiroannulation approach to access the spiro[benzo[b][1,4]oxazine-benzo[c]chromene skeleton is described in this contribution. A variety of spiro[5.5]-heterocyclic scaffolds were obtained in moderate to excellent yields under mild conditions. Key features of this protocol are good substrate scope, silver-free conditions, low catalyst loadings, easy handling under air and 100% atom economy. Furthermore, scale-up reactions and late-stage derivatizations highlight the potential synthetic utility of this methodology.

Restenosis after excimer laser coronary atherectomy and drug-coated balloon dilation in Takayasu's arteritis: a case report and review of the literature.

Takayasu's arteritis (TAK) is a rare chronic granulomatous arteritis that mainly affects the aorta and its major branches. Coronary artery (CA) involvement can be observed in 10-25% of TAK patients. We report a 21-year-old young female who was previously diagnosed with TAK and severe left main coronary artery (LMCA) stenosis and underwent numerous percutaneous coronary interventions (PCIs) in our hospital due to in-stent restenosis (ISR). This time, an excimer laser coronary atherectomy (ELCA) and drug-coated balloon (DCB) dilation was taken at the LMCA for the ISR. The blood flow was smooth after the operation, and she was symptom-free after discharge. Unfortunately, 5 months later, severe intimal hyperplasia was still seen in the stent of LMCA and left anterior descending (LAD) coronary artery. A coronary artery bypass graft surgery (CABG) was performed, and she has been symptom-free ever since. ELCA plus DCB is one of the novel ways we first reported. However, ensuring long-term inflammation control is equally important to restore blood flow. The combination of revascularization and anti-inflammation/immunosuppression is recommended to improve the outcomes of TAK patients with CA involvements.