Clinical characteristics of heavy alcohol consumption in young and middle-aged acute cerebral infarction: A 12-month follow-up study.

Objective: To investigate the clinical characteristics and prognosis of heavy alcohol consumption among young and middle-aged patients with acute cerebral infarction (ACI). Methods: A total of 263 young and middle-aged ACI patients were included in the study from June 2018 to December 2020 and classified into heavy drinkers and non-heavy drinkers. Multivariate logistic regression analysis was conducted to assess the association between ACI and heavy alcohol consumption, considering clinical characteristics and one-year post-discharge prognosis. Results: Among the patients, 78 were heavy drinkers. Heavy drinkers were more likely to consume alcohol 24 h before ACI onset (OR 4.03, 95 % CI 2.26-7.20), especially in the form of liquor (OR 3.83, 95 % CI 1.59-9.20), and had a higher risk of diastolic blood pressure ≥90 mmHg upon admission (OR 2.02, 95 % CI 1.12-3.64). In the one-year post-discharge prognosis, heavy drinkers had a greater likelihood of poor prognosis at 3 months (OR 2.31, 95 % CI 1.01-5.25), were less likely to quit drinking after discharge (OR 0.36, 95 % CI 0.19-0.66), and had a higher risk of recurrent cerebral infarction (OR 2.79, 95 % CI 1.14-6.84). Conclusions: Over the 12-month follow-up, young and middle-aged ACI patients with heavy alcohol consumption exhibited worse short-term prognosis. Controlling alcohol consumption levels may improve the prognosis of these patients.

Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways.

The interaction between programmed cell death ligand 1 (PD-L1), which is expressed on the surface of tumor cells, and programmed cell death 1 (PD-1), which is expressed on T cells, impedes the effective activation of tumor antigen-specific T cells, resulting in the evasion of tumor cells from immune-mediated killing. Blocking the PD-1/PD-L1 signaling pathway has been shown to be effective in preventing tumor immune evasion. PD-1/PD-L1 blocking antibodies have garnered significant attention in recent years within the field of tumor treatments, given the aforementioned mechanism. Furthermore, clinical research has substantiated the efficacy and safety of this immunotherapy across various tumors, offering renewed optimism for patients. However, challenges persist in anti-PD-1/PD-L1 therapies, marked by limited indications and the emergence of drug resistance. Consequently, identifying additional regulatory pathways and molecules associated with PD-1/PD-L1 and implementing judicious combined treatments are imperative for addressing the intricacies of tumor immune mechanisms. This review briefly outlines the structure of the PD-1/PD-L1 molecule, emphasizing the posttranslational modification regulatory mechanisms and related targets. Additionally, a comprehensive overview on the clinical research landscape concerning PD-1/PD-L1 post-translational modifications combined with PD-1/PD-L1 blocking antibodies to enhance outcomes for a broader spectrum of patients is presented based on foundational research.

Nanomaterials Boost CAR-T Therapy for Solid Tumors.

T cell engineering, particularly via chimeric antigen receptor (CAR) modifications for enhancing tumor specificity, has shown efficacy in treating hematologic malignancies. The extension of CAR-T cell therapy to solid tumors, however, is impeded by several challenges: The absence of tumor-specific antigens, antigen heterogeneity, a complex immunosuppressive tumor microenvironment, and physical barriers to cell infiltration. Additionally, limitations in CAR-T cell manufacturing capacity and the high costs associated with these therapies restrict their widespread application. The integration of nanomaterials into CAR-T cell production and application offers a promising avenue to mitigate these challenges. Utilizing nanomaterials in the production of CAR-T cells can decrease product variability and lower production expenses, positively impacting the targeting and persistence of CAR-T cells in treatment and minimizing adverse effects. This review comprehensively evaluates the use of various nanomaterials in the production of CAR-T cells, genetic modification, and in vivo delivery. It discusses their underlying mechanisms and potential for clinical application, with a focus on improving specificity and safety in CAR-T cell therapy.

Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications.

Immune checkpoint molecules play a pivotal role in the initiation, regulation, and termination of immune responses. Tumor cells exploit these checkpoints to dampen immune cell function, facilitating immune evasion. Clinical interventions target this mechanism by obstructing the binding of immune checkpoints to their ligands, thereby restoring the anti-tumor capabilities of immune cells. Notably, therapies centered on immune checkpoint inhibitors, particularly PD-1/PD-L1 and CTLA-4 blocking antibodies, have demonstrated significant clinical promise. However, a considerable portion of patients still encounter suboptimal efficacy and develop resistance. Recent years have witnessed an exponential surge in preclinical and clinical trials investigating novel immune checkpoint molecules such as TIM3, LAG3, TIGIT, NKG2D, and CD47, along with their respective ligands. The processes governing immune checkpoint molecules, from their synthesis to transmembrane deployment, interaction with ligands, and eventual degradation, are intricately tied to post-translational modifications. These modifications encompass glycosylation, phosphorylation, ubiquitination, neddylation, SUMOylation, palmitoylation, and ectodomain shedding. This discussion proceeds to provide a concise overview of the structural characteristics of several novel immune checkpoints and their ligands. Additionally, it outlines the regulatory mechanisms governed by post-translational modifications, offering insights into their potential clinical applications in immune checkpoint blockade.

A comparative study of fast-track versus [corrected] conventional surgery in patients undergoing laparoscopic radical cystectomy and ileal conduit diversion: Chinese experience.

Fast-track surgery (FTS), which combines various techniques with evidence-based adjustments, is aimed to reduce postoperative morbidity, attenuate surgical stress response, thereby accelerating recovery and shorting length of stay. To further investigate the effectiveness of fast-track surgery, we compared the short-term outcomes of laparoscopic radical cystectomy and ileal conduit diversion for Chinese bladder cancer patients with FTS or with CS in our hospital. Patients with bladder cancer were included and divided into two consecutive groups: CS group and FTS group. Duration to first flatus and regular diet, postoperative hospital days, hospital expense, incidence of complications and postoperative surgical stress response were compared. There was no significant difference between the two groups in age, sex, BMI and postoperative TNM classification. Compared with the CS group, the FTS group had significantly shorter duration to first flatus, time to regular diet, postoperative hospital days and hospital expense, less complications, lower white blood count (WBC) and serum of C-reactive protein (CRP) on postoperative day 5 and 7. Our study indicates that FTS program is safe and efficacious for Chinese patients undergoing laparoscopic radical cystectomy and ileal conduit diversion. It can accelerate recovery, reduce stress action, shorten postoperative hospitals days and reduce hospital expenses.