Exosomes: the next-generation therapeutic platform for ischemic stroke.

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood-brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

The emerging role of nuclear receptor coactivator 4 in health and disease: a novel bridge between iron metabolism and immunity.

Nuclear receptor coactivator 4 (NCOA4) has recently been recognized as a selective cargo receptor of ferritinophagy participating in ferroptosis. However, NCOA4 is also a coactivator that modulates the transcriptional activity of many vital nuclear receptors. Recent novel studies have documented the role of NCOA4 in healthy and pathogenic conditions via its modulation of iron- and non-iron-dependent metabolic pathways. NCOA4 exhibits non-ferritinophagic and iron-independent features such as promoting tumorigenesis and erythropoiesis, immunomodulation, regulating autophagy, and participating in DNA replication and mitosis. Full-length human-NCOA4 is composed of 614 amino acids, of which the N-terminal (1-237) contains nuclear-receptor-binding domains, while the C-terminal (238-614) principally contains a ferritin-binding domain. The exploration of the protein structure of NCOA4 suggests that NCOA4 possesses additional significant and complex functions based on its structural domains. Intriguingly, another three isoforms of NCOA4 that are produced by alternative splicing have been identified, which may also display disparate activities in physiological and pathological processes. Thus, NCOA4 has become an important bridge that encompasses interactions between immunity and metabolism. In this review, we outline the latest advances in the important regulating mechanisms underlying NCOA4 actions in health and disease conditions, providing insights into potential therapeutic interventions.

Phytochemicals targeting ferroptosis in cardiovascular diseases: Recent advances and therapeutic perspectives.

Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.

The Influence of Visceral Adiposity on Overall Survival: Exploring "Obesity Paradox" Among Hepatocellular Carcinoma Patients Who Receiving Immunotherapy.

Purpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions. Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models. Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI. Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.

Assessing the merits: an opinion on the effectiveness of simulation techniques in tumor subclonal reconstruction.

Summary: Neoplastic tumors originate from a single cell, and their evolution can be traced through lineages characterized by mutations, copy number alterations, and structural variants. These lineages are reconstructed and mapped onto evolutionary trees with algorithmic approaches. However, without ground truth benchmark sets, the validity of an algorithm remains uncertain, limiting potential clinical applicability. With a growing number of algorithms available, there is urgent need for standardized benchmark sets to evaluate their merits. Benchmark sets rely on in silico simulations of tumor sequence, but there are no accepted standards for simulation tools, presenting a major obstacle to progress in this field. Availability and implementation: All analysis done in the paper was based on publicly available data from the publication of each accessed tool.

Membranous nephropathy: pathogenesis and treatments.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

[Advances in Nanotechnology-Based Drug Delivery Systems in the Treatment of Hepatocellular Carcinoma].

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. METHODS: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. RESULTS: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. CONCLUSION: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. TRAIL REGISTRATION: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).

Familiarity of evidence based practices in Chinese caregivers of autistic children.

Although researchers have investigated special educators' and clinicians' knowledge and use of evidence-based practices (EBPs), there is very little research on caregivers' perception of the importance of EBPs for their autistic children. Moreover, there is even less research on how EBPs have been translated or disseminated in international communities not within the English-speaking, Western population. In order to provide appropriate support for caregivers of autistic children in all communities, we need more information to identify possible barriers that may affect caregiver involvement. We used a survey to ask 81 Chinese caregivers of autistic children in Guangzhou, China to investigate their familiarity with EBPs for autistic individuals and any external sources used inform their decision about treatment options for their autistic child. Results showed that 58.6% of the participants had no knowledge of what an EBP was and an additional 29.7% of the participants had heard of EBPs but not sure what they were. These results amplify the need for increased dispersion of ASD intervention knowledge to global communities and how to increase caregiver knowledge on treatment options for their autistic child.

Two-dimensional Perovskitoids Enhance Stability in Perovskite Solar Cells.

Two-dimensional (2D)/three-dimensional (3D) perovskite heterostructures have played a key role in advancing the performance of perovskite solar cells (PSCs)1,2. However, the migration of cations between 2D and 3D layers results in the disruption of octahedral networks that leads to degradation in performance over time3,4. We hypothesized that perovskitoids, with robust organic-inorganic networks enabled by edge- and face-sharing, could impede ion migration. We explored a set of perovskitoids of varying dimensionality, and found that cation migration within perovskitoid/perovskite heterostructures was suppressed compared to the 2D/3D perovskite case. Increasing the dimensionality of perovskitoids improves charge transport when they are interfaced with 3D perovskite surfaces - this the result of enhanced octahedral connectivity and out-of-plane orientation. The 2D perovskitoid (A6BfP)8Pb7I22 (A6BfP: N-aminohexyl-benz[f]-phthalimide) provides efficient passivation of perovskite surfaces and enables uniform large-area perovskite films. Devices based on perovskitoid/perovskite heterostructures achieve a certified quasi-steady-state power conversion efficiency of 24.6% for centimeter-area PSCs. We removed the fragile hole transport layers and showed stable operation of the underlying perovskitoid/perovskite heterostructure at 85°C for 1,250 hours for encapsulated large-area devices in an air ambient.

Current advances of oral cancer in Taiwan.

OBJECTIVES: To provide updated statistics of oral cancer incidence and mortality in Taiwan, and to describe recent developments for oral cancer control to reduce oral cancer incidence and mortality. METHODS: The Taiwan Cancer Registry Annual Report 2023, the Taiwan Cancer Registry Online Interactive Search System, and the 2023 Health Promotion Administration Annual Report are consulted and summarized. A literature search using PubMed was also conducted to identify Taiwan oral cancer control-related studies. RESULTS: Taiwan, with a long history of areca/betel quid chewing, has battled with oral cancer for decades. In 2021, the male lip and oral cavity cancer incidence is 29.77 (per 100,000 persons) and mortality is 11.25. Over these years, the male chewing prevalence was reduced to 6.2% in 2018. Taiwan has a sustained national oral cancer screening programme provided to high-risk groups biennially. CONCLUSIONS: Although the age-standardized incidence rates have been slowly decreasing since 2009, due to Taiwan's ageing population, the actual oral cancer burden is still stringent. The collaboration of multi-ministries and agencies on promoting areca nut and betel quid control, improving oral cancer awareness, and delivering cancer care remains essential to prevent oral cancer and reduce oral cancer deaths.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

BACKGROUND AND PURPOSE: The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). METHODS: This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). CONCLUSIONS: Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

Isospongian Diterpenoids from the Leaves of Amomum tsao-ko Promote GLP-1 Secretion via Ca2+/CaMKII and PKA Pathways and Inhibit DPP-4 Enzyme.

Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7% and 186.1% (60 µM). Mechanism study demonstrated that the GLP-1 stimulative effects of 2 and 3 were closely related with Ca2+/CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed moderate DPP-4 inhibitory activity with an IC50 value of 311.0 µM. Molecular docking verified the binding affinity of 1 with DPP-4 by hydrogen bonds between the γ-lactone carbonyl (C-15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao-ko, which showed antidiabetic potency by promoting GLP-1 secretion and inhibiting DPP-4 activity.

Unveiling the bidirectional role of MMP9: A key player in kidney injury.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic metalloenzymes that are involved in numerous pathological conditions, including nephropathy. MMP9, a member of the MMPs family, is categorized as a constituent of the gelatinase B subgroup, and its involvement in extracellular matrix (ECM) remodeling and renal fibrosis highlights its importance in the development and progression of renal diseases. The exact role of MMP9 in the development of kidney diseases is still controversial. This study investigated the dual role of MMP9 in kidney injury, discussing its implications in the pathogenesis of kidney diseases and investigating the design and mechanism of MMP9 inhibitors based on previous studies. This study provides an effective basis for the development of novel and selective MMP9 inhibitors for treating renal diseases.

Association between muscle strength and cardiometabolic multimorbidity risk among middle-aged and older Chinese adults: a nationwide longitudinal cohort study.

BACKGROUND: Cardiometabolic multimorbidity (CM) is emerging as a global health challenge. This study investigated the potential impact of muscle strength on the risk of CM in middle-aged and older Chinese adults. METHODS: In total, 7610 participants were identified from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was measured by absolute, relative grip strength (normalized for body mass index) and chair-rising time which were classified into three categories according to tertiles stratified by gender. Cox proportional hazards models were adopted to evaluate the effect of muscle strength on CM. RESULTS: During follow-up, 235(3.76%) participants from none cardiometabolic diseases (CMD), 140 (19.23%) from diabetes, 119 (21.17%) from heart disease, and 22 (30.56%) from stroke progressed to CM. In participants who had low relative grip strength, CM was more likely to occur in individuals with heart disease at baseline (HR: 1.89, 95%CIs: 1.10 to 3.23). Those with high chair-rising time had a higher risk of CM than those with low chair-rising time in the individuals with diabetes (HR: 1.85, 95%CIs:1.20 to 2.86) and with heart disease (HR: 1.67, 95%CIs:1.04 to 2.70). However, we did not observe an association between muscle strength and CM in participants without CMD or with stroke at baseline. CONCLUSIONS: In Chinese middle-aged and older adults, low relative grip strength was associated with a higher risk of CM in individuals with heart disease, while high chair-rising time was associated with a higher risk of CM in individuals with diabetes or heart disease.

Is it time to recommend AUC-based vancomycin therapeutic drug monitoring only? A cross-sectional survey in China.

Background: The latest published therapeutic drug monitoring (TDM) guidelines for vancomycin recommend changing trough-based monitoring to area under the concentration-to-time curve (AUC)-based monitoring. This study aimed to evaluate the implementation status and perceptions of vancomycin AUC-based TDM in China and to determine the challenges in performing AUC-based TDM. Methods: A nationwide cross-sectional survey was conducted in China using an online questionnaire. The questionnaire comprised a total of 25 questions with open- and closed-ended answers to collect information about the current implementation of vancomycin TDM and the participants' perceptions of these practices. The questionnaire responses were collected via the Questionnaire Star platform and analyzed. Results: A total of 161 questionnaires were completed by 131 hospitals and were included. Approximately 59.5% (78/131) of the surveyed hospitals conducted vancomycin TDM; however, only 10.7% (14/131) of these hospitals performed AUC-based vancomycin TDM. Of the eligible participants, 58.4% (94/161) had experience with vancomycin TDM, and only 37 participants (37/161, 23.0%) had the ability to estimate the AUC, primarily through Bayesian simulation (33/161, 20.5%). The participants considered the following challenges to implementing AUC-based monitoring: (1) the high cost of AUC-based monitoring; (2) inadequate knowledge among pharmacists and/or physicians; (3) the complexity of AUC calculations; (4) difficulty obtaining AUC software; and (5) unclear benefit of AUC-based monitoring. Conclusion: The majority of surveyed hospitals have not yet implemented AUC-based vancomycin TDM. Multiple challenges should be addressed before wide implementation of AUC-based monitoring, and guidance for trough-based monitoring is still needed.

Multi-Omics analysis elucidates tumor microenvironment and intratumor microbes of angiogenesis subtypes in colon cancer.

BACKGROUND: Angiogenesis plays an important role in colon cancer (CC) progression. AIM: To investigate the tumor microenvironment (TME) and intratumor microbes of angiogenesis subtypes (AGSs) and explore potential targets for antiangiogenic therapy in CC. METHODS: The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. K-means clustering was used to construct the AGSs. The prognostic model was constructed based on the differential genes between two subtypes. Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC, which was validated by immunofluorescence. Its biological functions were further explored in HUVECs. RESULTS: CC samples were grouped into two AGSs (AGS-A and AGS-B) groups and patients in the AGS-B group had poor prognosis. Further analysis revealed that the AGS-B group had high infiltration of TME immune cells, but also exhibited high immune escape. The intratumor microbes were also different between the two subtypes. A convenient 6-gene angiogenesis-related signature (ARS), was established to identify AGSs and predict the prognosis in CC patients. SLC2A3 was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs. CONCLUSION: Our study identified two AGSs with distinct prognoses, TME, and intratumor microbial compositions, which could provide potential explanations for the impact on the prognosis of CC. The reliable ARS model was further constructed, which could guide the personalized treatment. The SLC2A3 might be a potential target for antiangiogenic therapy.

Novel energy optimizer, meldonium, rapidly restores acute hypobaric hypoxia-induced brain injury by targeting phosphoglycerate kinase 1.

BACKGROUND: Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury. METHODS: We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression. RESULTS: The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones. CONCLUSION: These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.

Association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index and Adverse Clinical Outcomes in CAD Patients after PCI: Findings of a Real-World Study.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).