Search

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. [ABSTRACT FROM AUTHOR]

Pyroptosis provides a novel perspective for the design of anti‐tumor strategies. However, when pyroptosis reaches a plateau, its negative role becomes “defense” signaling to evade immune surveillance. Herein, a triblock polymeric micelles TPT@PIO NPs are reported, including a hydrophobic block backbone poly (propylene sulfide) (PPS), a hydrophobic side chain disulfide bond‐bearing indomethacin (MABHD‐IND), a hydrophilic block poly(ethylene glycol) methyl ether methacrylate (OEGMA), and an encapsulated hydrophobic drug topotecan (TPT) through hydrophobic forces, exhibit excellent stability and responsiveness to the oxidation‐reduction microenvironment. This dual treatment mode utilizes TPT to trigger the activation of the pyroptosis process and uses IND to eliminate the immune escape by inhibiting the COX‐2/PGE2 pathway, ultimately making the growth of tumors being inhibited via the synergy of chemotherapy and immunotherapy. Furthermore, the failure of the immunosuppressive network accelerates the infiltration of CD8+ T cells into the lungs and impedes the generation of tumor nodules. The changes in levels of cytokines caused by pyroptosis and the immune memory effect enhance the defense of transfer as well. In general, the ability of TPT@PIO NPs to regulate the Janus‐faced nature of pyroptosis acts as an indispensable role in suppressing tumor proliferation and metastasis. [ABSTRACT FROM AUTHOR]

Chemotherapy‐based combination regimens are recommended as first‐line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD‐OxPt (IV) nanoparticles (NPs) via host‐guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD‐OxPt (IV) NPs exhibit prolonged circulation in the blood and intra‐tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD‐OxPt (IV) NPs exhibited proton‐driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD‐OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53‐mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino‐like cell death and enhanced immunogenicity. Furthermore, DAS@CD‐OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis. [ABSTRACT FROM AUTHOR]

Expanding and enhancing the quality of consumption is crucial to satisfy the increasing demand for a higher standard of living. However, the rising risk of chronic diseases impacts not only the level of consumption but also impedes the optimization of consumption patterns. This research utilizes Staggered Difference-in-Differences (DID) and Difference-in-Differences-in-Differences (DDD) models to evaluate the effects of chronic disease shocks on both the levels and structures of household consumption, leveraging data from the China Family Panel Studies (CFPS) across four survey waves from 2012 to 2018. Additionally, the study examines the effects and mechanisms of the multi-level health insurance system in mitigating the impact of chronic disease shocks. The study discerns a significant decrease in household consumption expenditure, obstruction in the enhancement of consumption structures, and a constriction of consumption diversity attributable to chronic disease shocks. Heterogeneous analysis reveals that the impact of chronic shocks varies across factors such as age, capital endowment, urban versus rural residence, and the availability of healthcare resources. Moreover, the analysis highlights the heterogeneous mitigating effects of the multi-level health insurance system, particularly through diminishing out-of-pocket medical expenses and the propensity for precautionary savings. The findings accentuate the imperative for the enhancement and equalization of the multi-level health insurance system to fortify household consumption, offering significant policy insights for the realization of the "Healthy China" vision. JEL Classification : P36, D12. [ABSTRACT FROM AUTHOR]

Circadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually affect recovery after anesthesia. A retrospective cohort study initially included 107,406 patients (1 June 2016–6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome. Of 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median [interquartile range], 57 [46, 70] vs. 54 [43, 66], p < 0.001) and a higher Steward score (5.62 [5.61, 5.63] vs. 5.66 [5.65, 5.67], p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 [46, 70] vs. 54 [43, 66], p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, −3.20; 95% confidence interval, −3.55 to −2.86). Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection. In this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group. In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time. Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection. [ABSTRACT FROM AUTHOR]