Neuroprotective macromolecular methylprednisolone prodrug nanomedicine prevents glucocorticoid-induced muscle atrophy and osteoporosis in a rat model of spinal cord injury.

To address the adverse side effects associated with systemic high-dose methylprednisolone (MP) therapy for acute spinal cord injury (SCI), we have developed a N-2-hydroxypropyl methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP). Intravenous Nano-MP selectively targeted to the inflamed SCI lesion and significantly improved neuroprotection and functional recovery after acute SCI. In the present study, we comprehensively assessed the potential adverse side effects associated with the treatment in the SCI rat models, including reduced body weight and food intake, impaired glucose metabolism, and reduced musculoskeletal mass and integrity. In contrast to free MP treatment, intravenous Nano-MP after acute SCI not only offered superior neuroprotection and functional recovery but also significantly mitigated or even eliminated the aforementioned adverse side effects. The superior safety features of Nano-MP observed in this study further confirmed the clinical translational potential of Nano-MP as a highly promising drug candidate for better clinical management of patients with acute SCI.

Controlled Twill Surface Structure Endowing Nanofiber Composite Membrane Excellent Electromagnetic Interference Shielding.

Inspired by the Chinese Knotting weave structure, an electromagnetic interference (EMI) nanofiber composite membrane with a twill surface was prepared. Poly(vinyl alcohol-co-ethylene) (Pva-co-PE) nanofibers and twill nylon fabric were used as the matrix and filter templates, respectively. A Pva-co-PE-MXene/silver nanowire (Pva-co-PE-MXene/AgNW, PMxAg) membrane was successfully prepared using a template method. When the MXene/AgNW content was only 7.4 wt% (PM7.4Ag), the EMI shielding efficiency (SE) of the composite membrane with the oblique twill structure on the surface was 103.9 dB and the surface twill structure improved the EMI by 38.5%. This result was attributed to the pre-interference of the oblique twill structure in the direction of the incident EM wave, which enhanced the probability of the electromagnetic waves randomly colliding with the MXene nanosheets. Simultaneously, the internal reflection and ohmic and resonance losses were enhanced. The PM7.4Ag membrane with the twill structure exhibited both an outstanding tensile strength of 22.8 MPa and EMI SE/t of 3925.2 dB cm-1. Moreover, the PMxAg nanocomposite membranes demonstrated an excellent thermal management performance, hydrophobicity, non-flammability, and performance stability, which was demonstrated by an EMI SE of 97.3% in a high-temperature environment of 140 °C. The successful preparation of surface-twill composite membranes makes it difficult to achieve both a low filler content and a high EMI SE in electromagnetic shielding materials. This strategy provides a new approach for preparing thin membranes with excellent EMI properties.

Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.

Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes that link substrate release and opening of the cytoplasmic gate and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.

Drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics.

Background: The present study aimed to investigate the drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics. Research design and methods: A total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects. Results: The weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg-1 day-1 were recommended for patients with schizophrenia weighing 40-95 and 95-120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg-1 day-1 was recommended for those weighing 40-120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg-1 day-1 was recommended for patients with schizophrenia weighing 40-120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg-1 day-1 were recommended for those weighing 40-60 and 60-120 kg, respectively. Conclusion: This is the first investigation of the effects of fluoxetine on aripiprazole via drug-drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia.

Amino acid-induced synthesis of chiral AgAuPt nanoparticles with branched structure for circularly polarized enantioselective photoelectrocatalytic water splitting.

Chiral Plasmonic nanomaterials have gradually illustrated intriguing circularly polarized light (CPL)-dependent properties in photocatalysis due to their unique chiral optical activity. However, the connection between chiral characteristics and catalytic performance of these materials in cooperative systems is rarely reported and remains a challenge task. In this work, branched AgAuPt nanoparticles induced by L/d-cysteine (Cys) with strong and perfectly symmetric circular dichroism (CD) signals are synthesized. Chiral branched AgAuPt nanoparticles firstly exhibit superior typical electrocatalytic performance. In the photoelectrocatalytic system, chiral branched AgAuPt nanoparticles demonstrate selective catalytic water splitting performance. Specifically, chiral branched AgAuPt with related CPL irradiation exhibits enhanced acidic hydrogen evolution reaction (HER) performance. Under the continuous irradiation of related CPL, the chiral catalyst generates more heat, which further increases the catalytic activity. This contribution of heat is supported by density functional theory (DFT) calculation results. The changes in chiroptical activity during this process are recorded by variable temperature CD spectra. This work provides a novel paradigm for designing chiral catalysis systems and emphasizes the profound promise of chiral plasmonic nanomaterials as chiral catalysts.

Biportal endoscopic paraspinal decompression for epidural cement leakage removal: A technical note.

OBJECTIVE: We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy (UBE) for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression. METHODS: A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage. A transforaminal biportal endoscopic surgery was performed to remove the leaked cement, and the left L1 and bilateral L2 nerves were decompressed. RESULTS: The patient's postoperative clinical course was uneventful. CONCLUSIONS: A paraspinal approach that avoids a posterior approach reduces the need to remove stabilizing facet bone, is truly minimally invasive and does not involve an instrumented fusion, maybe a helpful addition in the minimally invasive spine surgeon's armamentarium.

Pd-catalyzed 5-exo-dig cyclization/etherification cascade of N-propargyl arylamines for the synthesis of polysubstituted furans.

A method for the synthesis of furans bearing indoline skeletons was developed via an intramolecular palladium-catalyzed 5-exo-dig cyclization/etherification cascade of N-propargyl arylamines containing a 1,3-dicarbonyl side chain. This method realized the first capture of vinyl carbopalladiums by ketones as O-nucleophiles and showed a wide range of substrate tolerability affording trisubstituted furans in various yields. The enantioselective version for this domino process and diverse derivatizations of the reaction products were also studied.

Recent advancement of sonogenetics: A promising noninvasive cellular manipulation by ultrasound.

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation with ultrasound, these proteins trigger a cascade of cellular activities and functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision and safety in disease treatment. This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, and beyond. Although current literature predominantly emphasizes ultrasonic neuromodulation, this review offers a comprehensive exploration of sonogenetics. We discuss ultrasound properties, the specific ultrasound-sensitive proteins employed in sonogenetics, and the technique's potential in managing conditions such as neurological disorders, cancer, and ophthalmic diseases, and in stem cell therapies. Our objective is to stimulate fresh perspectives for further research in this promising field.

Propofol Protects the Blood-Brain Barrier After Traumatic Brain Injury by Stabilizing the Extracellular Matrix via Prrx1: From Neuroglioma to Neurotrauma.

The purpose of this study is to explore the shared molecular pathogenesis of traumatic brain injury (TBI) and high-grade glioma and investigate the mechanism of propofol (PF) as a potential protective agent. By analyzing the Chinese glioma genome atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we compared the transcriptomic data of high-grade glioma and TBI patients to identify common pathological mechanisms. Through bioinformatics analysis, in vitro experiments and in vivo TBI model, we investigated the regulatory effect of PF on extracellular matrix (ECM)-related genes through Prrx1 under oxidative stress. The impact of PF on BBB integrity under oxidative stress was investigated using a dual-layer BBB model, and we explored the protective effect of PF on tight junction proteins and ECM-related genes in mice after TBI. The study found that high-grade glioma and TBI share ECM instability as an important molecular pathological mechanism. PF stabilizes the ECM and protects the BBB by directly binding to Prrx1 or indirectly regulating Prrx1 through miRNAs. In addition, PF reduces intracellular calcium ions and ROS levels under oxidative stress, thereby preserving BBB integrity. In a TBI mouse model, PF protected BBB integrity through up-regulated tight junction proteins and stabilized the expression of ECM-related genes. Our study reveals the shared molecular pathogenesis between TBI and glioblastoma and demonstrate the potential of PF as a protective agent of BBB. This provides new targets and approaches for the development of novel neurotrauma therapeutic drugs.

Healthy dietary patterns are associated with exposure to environmental chemicals in a pregnancy cohort.

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory efforts aimed at lowering environmental chemical exposure.

Effect of carbon nanoparticle suspension injection versus indocyanine green tracer in guiding lymph node dissection during radical gastrectomy (FUTURE-01): a randomized clinical trial.

BACKGROUND: Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively to sort lymph nodes (LNs) in gastric cancer patients. However, no study has compared the two tracers in gastric cancer patients. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted from January 2022 to March 2023. Patients with potentially resectable gastric cancer (cT1-4a N0/+ M0) were randomized to the CNSI or ICG group. RESULTS: This study enrolled 96 patients. Ninety patients were in the modified intention-to-treat population, including 46 patients (32 males and 14 females; mean [SD] age, 57.4 [9.4] years) in the CNSI group and 44 patients (31 males and 13 females; mean [SD] age, 60.8 [8.8] years) in the ICG group. The mean (SD) number of retrieved LNs was 69.8 (21.9) and 53.6 (17.2) in the CNSI and ICG groups, respectively (P<0.001). The mean (SD) number of retrieved micro-LNs was 19.9 (13.3) and 11.6 (9.9) in the CNSI and ICG groups, respectively (P=0.001). The mean (SD) number of metastatic LNs was 8.1 (11.9) and 5.2 (9.2) in the CNSI and ICG groups, respectively (P=0.19). CONCLUSIONS: Compared with ICG, CNSI can increase the number of LNs detected, especially micro-LNs. Both tracers have high diagnostic value for detecting metastatic LNs. CNSI-guided lymphography may be a superior method for improving the accuracy of LN dissection.

Complete 2,4,6-trichlorophenol degradation by anaerobic sludge acclimated with 4-chlorophenol: Synergetic effect of nZVI@BMPC and sodium lactate as an external nutrient.

Ball-milled plastic char supported nano zero-valent iron (nZVI@BMPC) and their application combined with anaerobic sludge for microbial dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP) were investigated. The XRD and FTIR analysis proved composition of zero valent states of iron, and the BET and SEM analysis showed that nZVI was uniformly distributed on the surface of BMPC. Successive addition of 1000 mg/L sodium lactate and nZVI@BMPC enhanced the acclamation of anaerobic sludge and resulted in the degradation of 4-CP within 80 days. The acclimated consortium with nZVI@BMPC completely degraded 2,4,6-TCP into CH4 and CO2, and the key dechlorination route was through 4-CP dechlorinaion and mineralization. The degradation rate of 2,4,6-TCP with nZVI@BMPC was 0.22/d, greater than that without nZVI@BMPC. The dechlorination efficiency was enhanced in the Fe2+/Fe3+ system controlled by nZVI@BMPC and iron-reducing bacteria. Metagenomic analysis result showed that the dominant de-chlorinators were Chloroflexi sp., Desulfovibrio, and Pseudomonas, which could directly degrade 2,4,6-TCP to 4-CP, especially, Chloroflexi bacterium could concurrently be used to mineralize 4-CP. The relative abundance of the functional genes cprA, acoA, acoB, and tfdB increased significantly in the presence of the nZVI@BMPC. This study provides a new strategy can be a good alternative for possible application in groundwater remediation.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

Sub-Nanosheet Induced Inverse Growth of Negative Valency Au Clusters for Tumor Treatment by Enhanced Oxidative Stress.

Cluster aggregation states are thermodynamically favored at the subnanoscale, for which an inverse growth from nanoparticles to clusters may be realized on subnanometer supports. Herein, we develop Au-polyoxometalate-layered double hydroxide (Au-POM-LDH) sub-1 nm nanosheets (Sub-APL) based on the above strategy, where sub-1 nm Au clusters with negative valence are generated by the in-situ disintegration of Au nanoparticles on POM-LDH supports. Sub-1 nm Au clusters with ultrahigh surface atom ratios exhibit remarkable efficiency for glutathione (GSH) depletion. The closely connected sub-1 nm Au with negative valence and POM hetero-units can promote the separation of hole-electrons, resulting in the enhanced reactive oxygen species (ROS) generation under ultrasound (US). Besides, the reversible redox of Mo in POM is able to deplete GSH and trigger chemodynamic therapy (CDT) simultaneously, further enhancing the oxidative stress. Consequently, the Sub-APL present 2-fold ROS generation under US and 7-fold GSH depletion compared to the discrete Au and POM-LDH mixture. Therefore, the serious imbalance of redox in the TME caused by the sharp increase of ROS and rapid decrease of GSH leads to death of tumor ultimately.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Computational modeling of the physical features that influence breast cancer invasion into adipose tissue.

Breast cancer invasion into adipose tissue strongly influences disease progression and metastasis. The degree of cancer cell invasion into adipose tissue depends on both biochemical signaling and the mechanical properties of cancer cells, adipocytes, and other key components of adipose tissue. We model breast cancer invasion into adipose tissue using discrete element method simulations of active, cohesive spherical particles (cancer cells) invading into confluent packings of deformable polyhedra (adipocytes). We quantify the degree of invasion by calculating the interfacial area At between cancer cells and adipocytes. We determine the long-time value of At vs the activity and strength of the cohesion between cancer cells, as well as the mechanical properties of the adipocytes and extracellular matrix in which adipocytes are embedded. We show that the degree of invasion collapses onto a master curve as a function of the dimensionless energy scale Ec , which grows linearly with the cancer cell velocity persistence time and fluctuations, is inversely proportional to the system pressure, and is offset by the cancer cell cohesive energy. When E c > 1 , cancer cells will invade the adipose tissue, whereas for E c < 1 , cancer cells and adipocytes remain de-mixed. We also show that At decreases when the adipocytes are constrained by the ECM by an amount that depends on the spatial heterogeneity of the adipose tissue.

[Research progress on the mechanisms of probiotics promoting wound healing].

Slow wound healing has been a troublesome problem in clinic. In China, traditional methods such as antibiotics and silver sulfadiazine are used to treat skin wound, but the abuse use has many disadvantages, such as chronic wounds and pathogen resistance. Studies have shown that the microorganisms with symbiotic relationship with organisms have benefits on skin wound. Therefore, the way to develop and utilize probiotics to promote wound healing has become a new research direction. In this paper, we reviewed the studies on the bacteriotherapy in the world, described how the probiotics can play a role in promoting wound healing through local wound and intestine, and introduced some mature probiotics products and clinical trials, aiming to provide foundations for further development of bacteriotherapy and products.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. Objective: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. Design, Setting, and Participants: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Exposures: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Main Outcomes and Measures: Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Results: Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. Conclusions and Relevance: In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.