Hao Wang

Pain represents a critical vital sign monitored in intensive care unit (ICU) patients. The facial action coding system (FACS) defines facial action units (AUs) and provides a structured framework for pain recognition. Currently, the most broadly used pain assessment method is the pain intensity scale developed by Prkachin and Solomon (PSPI), which relies on predefined AUs to quantify facial expressions. However, due to the influence of underlying diseases and facial texture variations in ICU patients, AUs can fail to transfer to clinical settings accurately. To address this problem, this study uses video sequences of pain states collected from 61 ICU patients under resting, daily, and procedural conditions by using an advanced AU detection system. By evaluating the AUs with statistical features and various classification models, this study identifies six key AUs that outperform the PSPI’s predefined AUs in terms of accuracy, precision, recall, and F1-score metrics. Further, this study explores the performance of various temporal self-learning networks in the pain assessment task, thus further validating the effectiveness of the identified AU combination. The results presented in this study demonstrate that using AU dynamic learning in combination with deep temporal analysis can improve the reliability of clinical pain assessment. Finally, this study offers a promising approach for automated pain monitoring systems in ICU settings.

Objective: The systemic immune-inflammation index (SII) has been linked to outcomes in various malignancies and has demonstrated utility in the diagnosis and prognosis of many conditions. This biomarker is gaining increasing recognition in the medical community. Understanding its developmental trajectory, critical areas of research, and future directions is essential for advancing its clinical application. However, there has been no literature bibliometric analysis on the SII. This study intended to visually analyze the research status and hotspots related to the SII. Methods: We utilized the Web of Science database to retrieve literature pertaining to the SII. Annual publication trends were statistically analyzed using Excel, VOSviewer, and CiteSpace for the visual analysis of authorship, institutional affiliations, countries, keywords, and co-cited references. Results: Two thousand seven hundred sixty-three publications were included. Fifteen thousand one hundred forty-eight authors contributed to these publications; 726 core authors represented 4.79% of the total. The leading countries were China (1532), Turkey (641), USA (91), Italy (86), and Japan (67), with the United States displaying the highest centrality score of 0.55. The top 3 institutions that contributed to the literature were the University of Health Sciences, Capital Medical University, and Sichuan University. Keyword analysis indicated that the research hotspots predominantly focused on tumors and their prognosis. Co-citation clustering revealed evolving themes, including prognostic significance, national health, myocardical infarction, covid-19 patient and disease activity, and multicenter study. Conclusion: The SII has garnered significant attention as a novel inflammation-related biomarker. However, further longitudinal and cross-sectional studies should be conducted to expand our understanding of its applications.

To explore the incidence, risk factors and clinical effects of acute kidney injury (AKI) in elderly patients with hip fracture admitted to the ICU postoperatively and assess the predictive value of risk factors. We retrospectively analyzed consecutive elderly patients with hip fracture who underwent surgery and were admitted to the ICU at Beijing Jishuitan Hospital, Capital Medical University (October 2022-August 2023). Patients were divided into AKI group and non-AKI group according to whether AKI occurred. Demographic, preoperative, intraoperative, and postoperative data were compared. Multivariate logistic regression identified AKI risk factors, and receiver operating characteristic (ROC) curves evaluated their predictive ability. Among 156 patients, 31 (19.9%) developed AKI. Multivariate logistic regression analysis showed that female sex, intraoperative blood transfusion, postoperative albumin level and postoperative Acute Physiology and Chronic Health Evaluation (APACHE) II score were independent risk factors for AKI (p < 0.05). ROC curve showed that the combination of these four indicators and postoperative APACHE II score could effectively predict AKI occurrence, and the area under the curve (AUC) was 0.93 and 0.86, respectively (p < 0.05). Patients in the AKI group stayed in ICU longer than those in the non-AKI group (p < 0.05). The incidence of AKI was high in elderly patients with hip fracture admitted to ICU after surgery. The combination of being female, receipt of intraoperative blood transfusion, postoperative albumin level and postoperative APACHE II score had good predictive value for AKI. The occurrence of AKI resulted in prolonged ICU stay.

Introduction: Intra‐abdominal candidiasis (IAC) still has a high mortality rate despite prompt antifungal therapy due to immunosuppression. T cell exhaustion is an important manifestation of immunosuppression. This study aimed to explore the expression pattern of exhaustion‐related molecules in patients with IAC and determine the possible association between dynamic trends and prognosis.Methods: Patients with IAC were enrolled, and non‐IAC critically ill patients were included as controls. Peripheral blood mononuclear cells (PBMCs) were analysed by flow cytometry to determine the expression levels of T cell exhaustion‐related markers. T cells isolated from PBMCs were stimulated by IL‐2 in α‐CD3/α‐CD28 medium to compare intracellular cytokine production and proliferative capacity.Results: A total of 34 patients with IAC and 35 controls were enrolled in this study. Patients with IAC had a significant decrease in lymphocytes. CD4+ and CD8+ T cells from patients with IAC had a significantly higher level of immune checkpoint molecules, such as programmed cell death protein 1 (PD‐1), cytotoxic T‐lymphocyte antigen 4 (CTLA4), and B and T lymphocyte attenuator (BTLA), and exhibited a consistently impaired cytokine‐secreting function. Increased exhaustion‐associated molecules and deteriorating dysfunction were detected in non‐survivors, while survivors demonstrated the opposite tendency. Patients with impaired granzyme B (GZMB) production function who died from IAC over the course of the disease had higher levels of PD‐1 expression in CD8+ T cells.Conclusions: T cells from patients with IAC displayed an immunosuppressive phenotype of T cell exhaustion. Sustaining exhaustion status and deteriorated dysfunction were associated with poor prognosis. Persistently increased PD‐1 expression and impaired GZMB secretion in CD8+ T cells were linked to worse outcomes. Immunoadjuvants reversing T cell exhaustion have promising prospects in treating IAC and improving prognosis.

Aims: to clarify the endoplasmic reticulum stress (ERS) status of CD4+ T lymphocytes in sepsis patients, particularly elderly individuals aged over 65 years, and to elucidate its association with mTOR-mediated autophagic-lysosomal disorder.Methods: 62 sepsis patients were enrolled from January 1 to July 31, 2024. Peripheral blood mononuclear cells (PBMCs) were isolated within 24 hours post-enrollment. flow cytometry was used to quantify the expression levels of ERS markers (CHOP and GRP78) and mTOR-mediated autophagic-lysosomal fusion markers (mTOR, LC3II and P62) on CD4+ T lymphocytes. These markers were compared between sepsis and non-sepsis patients, elderly and non-elderly sepsis patients, survivors and non-survivors based on in-hospital mortality. The correlations between CHOP mean fluorescence intensity (MFI) and CD4+ T lymphocyte count, LC3II MFI, and P62 MFI were also analyzed.Results: Compared to non-septic controls, sepsis patients exhibited significantly higher CHOP and GRP78 MFIs (210.9 versus 142.9, P<0.001 and 279.1 versus 223.7, P=0.045). Within the sepsis group, elderly patients and non-survivors showed significantly higher CHOP and GRP78 MFIs (334.4 versus 164.2, P<0.001 and 374.3 versus 218.6, P<0.001; 390.8 versus 177.6, P<0.001 and 389.1 versus 227.0, P<0.001). CHOP MFI on CD4+ T lymphocytes showed significant correlations with LC3II and P62 MFIs in sepsis patients (Pearson’s correlation r=0.657, p<0.001 and r=0.811, P<0.001), elderly sepsis patients (r=0.644, P<0.001 and r=0.710, P<0.001), and non-survived elderly sepsis patients (r=0.897, P<0.001 and r=0.772, P=0.009).Conclusion: ERS in CD4+ T cells was enhanced in sepsis patients, particularly in elderly and non-survived individuals; ERS is strongly associated with mTOR-mediated autophagic-lysosomal disorder.Clinical trial registration: chictr.org.cn, identifier ChiCTR2300074175.

Background: Frailty is associated with poor outcomes in elderly sepsis patients. This study investigated the relationship between Frailty Index-laboratory (FI-lab) and lymphocyte patterns in predicting 28-day mortality among elderly sepsis patients.Methods: We conducted a multicenter prospective observational study in four tertiary hospitals in Beijing, China. FI-lab was calculated using 24 laboratory parameters. Peripheral blood lymphocyte subsets were measured at ICU admission. Lymphocyte count trajectories were classified into four phenotypes based on patterns during the first 72 hours. The primary outcome was 28-day mortality.Results: Among 1,197 patients (mean age 74.6 ± 7.4 years), those with high FI-lab risk showed higher mortality (22.2%) than intermediate (12.0%) and low-risk groups (6.1%). Age-stratified analysis demonstrated consistent FI-lab prognostic value in both 65–79 years (OR 2.18) and ≥80 years (OR 2.47) groups. All lymphocyte subset counts were lower in non-survivors, particularly natural killer cells. In multivariable analysis, high FI-lab risk (OR 2.31), APACHE-II scores (OR 1.08), heart rate (OR 1.01), NK cell count (OR 0.994), and pulmonary infection (OR 1.96) independently predicted 28-day mortality. A combined model incorporating these variables showed superior discriminative ability (AUC=0.788) with excellent internal validation (optimism-corrected AUC=0.775).Conclusions: FI-lab independently predicts mortality in elderly sepsis patients and correlates with lymphocyte abnormalities. When comprehensive immune assessment is unavailable, lymphocyte trajectory patterns offer a practical approach for risk stratification.

Background: Sepsis induces profound derangements in the immune system, including lymphopenia, which correlates with immunosuppression and poor prognosis. However, most evaluations of immunosuppression in sepsis patients rely on static, sporadic lymphocyte counts, lacking dynamic modeling over the disease course. This study aimed to apply latent class mixed modeling on longitudinal lymphocyte counts to uncover heterogeneous trajectory phenotypes in sepsis patients and assess their predictive value for clinical outcomes.Results: Four lymphocyte trajectory phenotypes were identified in the retrospective cohort (n=2,149) and externally validated (n=2,388): high–declining (α, 3.8%), stable–medium (β, 69.3%), high–increasing (γ, 3.2%), and stable–low (δ, 23.8%). The α phenotype exhibited the highest disease severity and mortality (25.9%) compared with other phenotypes in both cohorts. In the prospective cohort (n=1,056), all lymphocyte subset counts differed among phenotypes on admission (P <.001) and were lower in non-survivors (P<.05). Multivariable regression demonstrated that age, Acute Physiology and Chronic Health Evaluation-II score, heart rate, natural killer cell count, infection source, and lymphocyte trajectory phenotype were independent predictors of 28-day mortality. A nomogram combining these variables provided individualized risk estimations.Conclusions: The lymphocyte trajectories delineated novel dynamic phenotypes associated with divergent sepsis outcomes. Incorporating longitudinal trajectory modeling and lymphocyte subsets may improve prognostic risk assessment and guide the selection of immunotherapies tailored to specific immune phenotypes in sepsis patients.Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=18277, identifier ChiCTR-40 ROC-17010750.

Background: The aim of this study was to clarify the relationship between expression level of CTLA-4 on CD4⁺ T cells and sepsis-associated immunosuppression (SAI), and to elucidate the possible mechanism of mTOR pathway mediated autophagic-lysosomal disorder in regulating CTLA-4 expression.Methods: We enrolled 63 sepsis patients admitted to our ICU between January 1 and June 30, 2023. Peripheral blood mononuclear cells were isolated from the patients within 24 hours of recruitment. Expression levels of mTOR, P62, LC3II, and CTLA-4 on circulating CD4⁺ T lymphocytes were quantitated using flow cytometry. The association of these markers and relationship between CTLA-4 expression and the incidence of SAI and 28-day mortality were comprehensively analyzed.Results: Compared with non-immunosuppressed patients with sepsis, patients with SAI had a higher 28-day mortality rate (37.5% vs 13.0%, P=0.039) and higher CTLA-4 mean fluorescence intensity (MFI) on CD4⁺ T cells (328.7 versus 78.7, P+ cells was independently associated with the occurrence of SAI (95% confidence interval: 1.00–1.14, P=0.044). In patients with sepsis and SAI, non-survivors had higher CTLA-4 expression than survivors (sepsis: 427.5 versus 130.6, P=0.002; and SAI: 506.7 versus 225.2, P+ T cells were statistically higher in patients with SAI than in non-immunosuppressed patients (267.2 versus 115.9, P+ T cells was markedly associated with the incidence of SAI and had great relevance to 28-day mortality. mTOR pathway mediated autophagic-lysosomal disorder showed significant association with CTLA-4 expression.

The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis.