To explore the genetic characteristics of familial Parkinson’s disease (PD)-related genes and construct a model of the gene signatures to guide the prognosis and treatment of patients with skin cutaneous melanoma (CMM).

① By analyzing the TCGA and GTEx databases, the expression differences of familial PD-related genes were compared between melanoma and normal tissues. The GEPIA2 database was used to analyze the expression differences of related genes across different TNM stages and Clark levels. ② Based on the TCGA database, a signature model containing 7 key genes was established using prognostic forest plot, LASSO regression model, and risk factor analysis. Internal and external validation of this model was performed, and GO enrichment and KEGG pathway enrichment analyses were conducted for these genes. ③ Based on the TIMER database, the impacts of gene mutations in the prognostic model on immune cell infiltration in the tumor microenvironment (TME) were analyzed. ssGSEA heatmaps were employed to analyze differences in immune cell subsets between high-risk and low-risk groups. Through PD-1 immune checkpoint inhibitor treatment response analysis, external dataset validation, and half-maximal inhibitory concentration (IC50) values of different drugs, possible differences in drug treatment efficacy between high-risk and low-risk groups were investigated. ④ Western blotting and RT-qPCR were utilized to detect the protein expression and relative mRNA expression differences of the genes in this prognostic model between normal human melanocyte cell line PIG1 and human melanoma cell line A375.

① Analysis of the TCGA and GTEx databases revealed that, except for PARK14 (PLA2G6), all familial PD-related genes showed significant expression differences between melanoma tissues and normal tissues. Analysis of the HPA database found that the protein expression of familial PD-related genes was either up-regulated or down-regulated in melanoma samples compared to normal tissues. Analysis of the GEPIA2 database for the expression of these genes across different TNM stages and Clark levels also found differential expression in some genes. ② COX regression analysis based on TCGA database identified that expression levels of 13 genes could predict overall survival in melanoma patients. LASSO regression analysis of this data constructed a melanoma prognostic model containing 7 familial PD-related genes (LRRK2, UCHL1, SNCA, VPS13C, SPR, EIF4G1, FBXO7). The prognostic risk scores for all patients were calculated using a risk factor contingency plot, and then the patients were divided into high-risk and low-risk groups based on the median risk score (-0.145). The results showed that the high-risk group had a significantly worse survival rate, while the low-risk group exhibited a longer survival time. Internal validation of the model in the TCGA cohort: the calibration curves for the 3-year and 5-year nomograms showed that the predicted curves for melanoma patient prognosis were very close to the actual curves. External validation in GEO cohorts: 3 datasets from the GEO database containing complete clinical data and gene expression matrices (GSE19234, GSE22153, and GSE53118) were selected. Based on the prognostic model's risk score, the sensitivity and specificity on the ROC curve were better than TNM staging. GO and KEGG pathway enrichment analyses found that the 7 genes were mainly enriched in pathways related to tumorigenesis and tumor immunity, such as phosphorylation, programmed cell death, and cell cycle, suggesting the prognostic model is associated with tumorigenesis and immunity. ③ GSVA scoring revealed that these 7 genes were enriched in pathways related to tumorigenesis and anti-tumor immunity. CD8⁺ T cells, cytotoxic cells, and Th1 cells, which can inhibit tumor growth, were more infiltrated in the low-risk group. Meanwhile, the IC₅₀ values for nilotinib, BIBW2992, bleomycin, bortezomib, dasatinib, and MK-2206 were lower in tumor cells from low-risk group patients (P<0.05). ④ RT-qPCR and Western blotting analysis were used to verify the relative expression differences of these 7 genes at the transcriptional and translational levels in A375 and PIG1 cells. The experimental results showed that LRRK2 and UCHL1 were almost not expressed in both A375 and PIG1 cells. Meanwhile, compared to normal melanocytes, the mRNA expression of SNCA, VPS13C, SPR, eIF4G1, and FBXO7 genes was significantly up-regulated in melanoma cells (P<0.05). The protein expression of SPR, EIF4G1, and FBXO7 was significantly upregulated (P<0.05).

The 7-gene signature prognostic model developed in this study can effectively assess prognosis and treatment efficacy in CMM patients.

To investigate whether the accuracy of artificial intelligence (AI)-assisted preoperative planning for total knee arthroplasty (TKA) is non-inferior to computer-assisted manual preoperative planning completed collaboratively by 3D engineers and orthopedic surgeons, and to evaluate the impact of age on the accuracy of AI-based planning.

This study adopted a retrospective, cross-sectional comparative design. Data were retrospectively collected from 127 patients who underwent TKA at the First Affiliated Hospital of Army Medical University between December 2022 and September 2023. They were divided into a ≤60 years group (40 to 60 years old, n=22) and an >60 years group (61 to 80 years old, n=105) based on age. All patients underwent both AI-assisted preoperative planning (AI planning) and computer-assisted manual preoperative planning (conventional planning). Hip-knee-shaft angle (HKS), femoral resection difference, tibial resection difference, femoral rotation angle, and prosthesis size data from AI planning, conventional planning, and actual intraoperative measurements, as well as time, manpower, and economic costs of AI planning and conventional planning were compared between the 2 planning methods. The non-inferiority margin was set as resection angle difference ≤1°, resection thickness difference ≤1 mm, and prosthesis size difference ≤1.

Compared with the conventional planning, the AI planning showed a mean increase of 0.8°±1.2° in HKS (Cohen’s d=0.4, 95%CI: 0.2 to 0.7), a mean increase of 1.1±1.8 mm in femoral resection difference (Cohen’s d=0.5, 95%CI: 0.3 to 0.8), and a mean increase of 0.6±1.7 mm in tibial resection difference (Cohen’s d=0.3, 95%CI: 0.0 to 0.5). The lower limits of 95%CI for these above standardized mean differences were all greater than their corresponding negative non-inferiority margins. In comparison with the conventional planning, the AI planning in the ≤60 years group showed no significant differences in HKS, tibial resection difference, and femoral rotation angle (P>0.05), whereas in the >60 years group, only femoral resection difference of AI planning exceeded the non-inferiority margin (with a mean increase of 1.1 mm, P<0.05). For prosthesis size prediction, the AI planning achieved 73.2% femoral prosthesis and 87.4% tibial prosthesis predictions with size differences not exceeding 1, while conventional planning achieved 81.9% femoral prosthesis and 90.6% tibial prosthesis predictions with size differences not exceeding 1, with no significant difference between the 2 planning methods (P>0.05). The time consumed for AI planning was significantly shorter than that for conventional planning (27.4±4.1 vs 45.3±8.5 min, P<0.05). Moreover, AI planning required no additional labor and equipment costs, with no additional manpower or equipment costs (0 vs 3 000 Yuan/case).

AI-assisted preoperative planning for TKA s demonstrates non-inferior accuracy compared with conventional planning, with superior performance particularly in patients under 60 years, and significant advantages in time and economic costs.

To perform in-depth integration and analysis of cancer multi-omics data and clinical data to enhance the predictive capability for cancer prognosis.

Multi-omics data (mRNA, lncRNA, and miRNA profiles) and clinical data for 3 cancer types, namely ovarian cancer, liver cancer, and colorectal cancer, were retrieved from The Cancer Genome Atlas (TCGA) database. A novel cancer prognosis prediction model, MoACG (Multi-omics Attention Clinical Gating Model), was constructed based on the self-attention mechanism to explore potential associations among different omics layers, and gated fusion was employed to adaptively integrate multi-omics information with clinical information(age, sex, and treatment modality) . The effectiveness of the model was validated through comparison with multiple machine learning methods, and the interpretability algorithm DeepLIFT was utilized to quantify gene contributions to the model and identify core prognostic genes.

In the ovarian cancer, liver cancer, and colorectal cancer datasets, five-fold cross-validation yielded the area under curve (AUC) values of receiver operating characteristic (ROC) curve of (0.793±0.042), (0.791±0.065), and (0.789±0.086), respectively, and the AUC values of precision-recall curve (AUPR) were (0.915±0.020), (0.855±0.058), and (0.917±0.039), respectively. The comprehensive performance surpassed that of 9 other machine learning models. Ablation experiments demonstrated that the 3-omics data integration model exhibited optimal predictive performance across all cancer types. The DeepLIFT algorithm identified MED8, DLGAP4, and NABP2 as genes associated with liver cancer, showing high concordance with existing research findings and effectively stratifying patient survival risk based on expression levels (P<0.005).

Compared with previous studies, the MoACG model, constructed by integrating multi-omics and clinical data, effectively enhances the predictive performance for cancer prognosis, thereby providing a novel approach for cancer diagnosis, treatment, and prognostic research.

This study aims to clarify the characteristics and temporal patterns of colonic barrier damage in mice following a single simulated high-intensity exercise in hot and humid environment, and further investigate the protective effects of baicalein (BAI) intervention on colonic injury, thereby providing experimental evidence for the development of medical protection time windows and pharmaceutical intervention protocols for personnel engaged in high-intensity exercise and operations in hot and humid environments.

①Thirty SPF-grade 8-week-old male C57BL/6J mice were randomly divided into 5 groups (n=6): control group, 30 min post-exercise group, 4 h post-exercise group, 12 h post-exercise group, and 24 h post-exercise group. The mice in the exercise groups were subjected on a treadmill in a heat chamber (temperature: 38℃, humidity: RH 75%) at 80% maximal exercise velocity (Vmax) (exercise 12 min, rest 8 min, 3 cycles; slope 10°). Subsequently, the colon tissues were harvested for morphological observation by HE staining in each group; ELISA was used to detect the serum levels of inflammatory factors (TNF-α, IL-6, IL-10, and IL-1β) to observe the inflammatory response of each group. Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide (LPS) were detected to observe intestinal permeability; Microassay was performed to determine the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), as well as the activity of catalase (CAT) and superoxide dismutase (SOD) in the colon tissues; RT-qPCR was applied to detect the expression levels of intestinal tight junction protein related genes Occludin, ZO-1, Claudin-1, inflammation and oxidative stress related genes Tlr4, TNF-α, IL-1β, IL-6, IL-10, heme oxygenase-1 (HO-1), and superoxide dismutase1 (SOD1), as well as key transcription factors HSF1, NF-κB, PARP-1, and NRF2 in heat stress regulation; Western blotting was utilized to detect the protein of colonic tight junction protein Occludin. ② For BAI intervention study, 24 SPF-grade 8-week-old male C57BL/6J mice were randomly divided into 4 groups (n=6) control group, exercise group (high temperature and high humidity exercise, gavage with deionized water 200 μL), exercise+low- and high-dose intervention groups (BAI gavage 200 μL at 10 and 40 mg/kg per day). At 4 h after the end of exercise, colonic and blood samples were collected for serum levels of urea nitrogen (BUN) content, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) to evaluate the safety of BAI. Other detection sites, indicators, and methods were the same as aforementioned.

① The core body temperature was significantly elevated in the exercise group (P<0.05); the structural damage, along with inflammatory cell infiltration was observed in colonic mucosa; the expression of colon Occludin, ZO-1, and Claudin-1 was downregulated (P<0.05), and the protein level of Occludin was decreased (P<0.05), and the serum levels of I-FABP and LPS were increased (P<0.05); The serum levels of TNF-α, IL-1β, IL-6, and IL-10 were increased (P<0.05), and the expression of IL-1β and IL-10 in the colon was upregulated (P<0.05); The concentration of MDA was increased (P<0.05), while the concentration of GSH and the activities of CAT and SOD were decreased (P<0.05); The expression of HSF1, PARP-1, NF-κB, Tlr4, TNF-α, IL-6, and SOD1 in the colon was upregulated (P<0.05), while the expression of NRF2 and HO-1 was downregulated (P<0.05). These changes were present at 30 min post-exercise, most prominent at 4 h post-exercise, and markedly recovered by 24 h. ② After BAI intervention, the core body temperature was significantly decreased (P<0.05), and the serum levels of ALT and AST were decreased (P<0.05); colonic mucosal injury was alleviated; the expression of Occludin at mRNA and protein levels in the colonic tissues were increased (P<0.05); the expression of ZO-1 and Claudin-1 were upregulated (P<0.05), and serum levels of I-FABP and LPS were decreased (P<0.05); the serum level of IL-1β was decreased (P<0.05), and the expression of IL-1β in the colon was downregulated (P<0.05); The concentration of MDA was decreased (P<0.05), while the concentration of GSH and activities of CAT and SOD in the colon were increased (P<0.05); The expression of HSF1, PARP-1, NF-κB, Tlr4, TNF-α, and IL-6 in the colon was downregulated (P<0.05), while the expression of NRF2 and HO-1 was upregulated (P<0.05). These results indicated that BAI possesses anti-inflammatory and antioxidant effects, with better efficacy in the low-dose group.

Peak colonic barrier injury occurs at 4 h after simulated high-intensity exercise in a hot and humid environment, and prophylactic use of BAI (10 mg/kg per day) can significantly inhibit inflammation and oxidative stress and alleviate injury, providing evidence for time windows and intervention basis for colonic injury induced by heat stress.

To investigate the impact of different sedation strategies on short-term outcomes in intensive care unit (ICU) patients receiving invasive mechanical ventilation (IMV), and to assess whether these effects differ in special populations such as the elderly, those with malignancy, or hepatic impairment.

This retrospective observational cohort study utilized data from 2 large critical care databases, MIMIC-IV (v2.2) and eICU-CRD (v2.0). Inclusion criteria were: age ≥18 years; endotracheal intubation and IMV within 48 h after ICU admission; ICU length of stay (LOS) ≥48 h; initiation of a single-agent sedation strategy (dexmedetomidine, propofol, or benzodiazepines) from 2 h before to 48 h after intubation. Patients receiving combined sedatives, undergoing re-intubation, or with single-drug sample sizes <100 were excluded. The primary outcome was time to extubation; secondary outcomes included in-hospital mortality, ICU LOS, incidence of delirium, and major adverse cardiovascular events (MACEs). Inverse probability of treatment weighting (IPTW) based on gradient boosting machine algorithms was employed to control confounding bias, followed by augmented inverse probability weighting (AIPW) doubly robust models to estimate average treatment effects (ATE), odds ratios (ORs), and 95% confidence intervals (CIs). Prespecified subgroup analyses were applied to examine interactions with age, malignancy, and hepatic status.

A total of 12 561 patients were enrolled, comprising 1 111 in the dexmedetomidine group, 8 021 in the propofol group, and 3 429 in the benzodiazepine group. After IPTW weighting, baseline variables achieved overall balance across groups. In the AIPW doubly robust models, compared with the dexmedetomidine group, the propofol group demonstrated prolonged time to extubation by 0.782 d (ATE=0.782 d, 95%CI: 0.769 to 0.796, P<0.001), and the benzodiazepine group by 1.791 d (ATE=1.791 d, 95%CI: 1.779 to 1.804, P<0.001); compared with benzodiazepines, the propofol group showed shortened extubation time by 1.009 d (ATE=-1.009 d, 95%CI: -1.018 to -1.000, P<0.001). For secondary outcomes, compared with dexmedetomidine, both propofol and benzodiazepines were associated with increased risk for in-hospital mortality (propofol: OR=1.905, 95%CI: 1.647 to 2.201, P<0.001; benzodiazepines: OR=2.768, 95%CI: 2.262 to 3.388, P<0.001) and for delirium (propofol: OR=1.905, 95%CI: 1.428 to 2.541, P<0.001; benzodiazepines: OR=2.382, 95%CI: 1.681 to 3.376, P<0.001). Additionally, ICU LOS was prolonged by 0.367 d and 1.012 d in the propofol and benzodiazepine groups, respectively (propofol: ATE=0.367 d, 95%CI: 0.351 to 0.382, P<0.001; benzodiazepines: ATE=1.012 d, 95%CI: 0.996 to 1.029, P<0.001), and the total incidence of MACEs increased by 6.527 and 15.199 events (propofol: ATE=6.527 events, 95%CI: 6.112 to 6.942, P<0.001; benzodiazepines: ATE=15.199 events, 95%CI: 14.727 to 15.671, P<0.001). Regarding ventilator-associated pneumonia (VAP), propofol was associated with a lower risk than dexmedetomidine (OR=0.722, 95%CI: 0.648 to 0.805, P<0.001), whereas no significant difference was observed between benzodiazepines and dexmedetomidine (OR=1.082, 95%CI: 0.934~1.252, P=1.000). Subgroup and interaction analyses revealed significant interactions between sedation strategy and malignancy (P-for-interaction=0.001) and moderate-to-severe liver disease (P-for-interaction=0.048). Among patients with malignancy, propofol showed a trend toward shorter time to extubation than dexmedetomidine (ATE=-1.326 d, 95%CI: -2.732 to -0.080, P=0.064); similarly, in patients with moderate-to-severe liver disease, propofol also demonstrated a trend toward shorter extubation time than dexmedetomidine (ATE=-1.232 d, 95%CI: -2.939 to -0.475, P=0.157), suggesting attenuated or even reversed benefits of dexmedetomidine in these special populations.

In ICU patients receiving invasive mechanical ventilation, dexmedetomidine, is associated with shorter time to extubation and lower risks of in-hospital mortality, delirium, and cardiovascular adverse events compared with propofol and benzodiazepines. However, these advantage of dexmedetomidine are diminished among patients with malignancy or moderate-to-severe liver disease.

To elucidate the specific role of Ras-related C3 botulinum toxin substrate 2 (RAC2) in neuronal apoptosis induced by cerebral ischemia-reperfusion (CIR), and investigate the molecular mechanisms underlying its regulation of apoptosis.

① Cell culture and grouping (n=5): mouse hippocampal neuronal cell line HT22 was divided into normal control (NC) and oxygen-glucose deprivation/reoxygenation (OGD/R) groups. The NC group was maintained under standard culture conditions, while the OGD/R group was subjected to 8 hours’ OGD/R. Cell proliferation was assessed using CCK-8 assay and EdU staining, and cell apoptosis was evaluated by flow cytometry. Western blotting was performed to measure the protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, cleaved poly(ADP-ribose) polymerase-1 (PARP-1), RAC2, and extracellular signal-regulated kinase (ERK)/p-ERK. Quantitative real-time PCR (qRT-PCR) was applied to detect the mRNA level of RAC2. ② Gene knockdown: HT22 cells were transfected with sh-RAC2 or non-targeting control shRNA (sh-NC) before OGD/R treatment. Subsequently, the cells were divided into OGD/R:sh-NC and OGD/R:sh-RAC2 groups (n=5). Apoptosis-related proteins were detected by Western blotting. ③ Pathway validation: The ERK inhibitor FR180204 was employed to establish 4 groups (n=5): NC, OGD/R, FR180204 alone, and FR180204+OGD/R (pretreated with FR180204 followed by OGD/R treatment). Expression of cleaved caspase-3, RAC2, and p-ERK was analyzed with Western blotting.

①Compared with the NC group, OGD/R treatment significantly inhibited HT22 cell proliferation and increased apoptotic rates (P<0.05). OGD/R upregulated pro-apoptotic proteins (Bax, cleaved PARP-1, and cleaved caspase-3), downregulated the anti-apoptotic protein Bcl-2, and markedly elevated RAC2 expression at both mRNA and protein levels (P<0.05). ② Specific knockdown of RAC2 (sh-RAC2 group) partially restored Bcl-2 expression and attenuated OGD/R-induced upregulation of Bax and cleaved PARP-1 compared with the OGD/R group (P<0.05). ③ OGD/R treatment activated the ERK signaling pathway (elevated p-ERK/ERK ratio), upregulated RAC2 expression, and promoted caspase-3 cleavage compared with the NC group (P<0.05). Conversely, pretreatment with FR180204 effectively blocked OGD/R-induced RAC2 upregulation and caspase-3 activation compared with the OGD/R group (P<0.05).

RAC2 plays a key role in CIR-induced neuronal apoptosis by modulating the Bcl-2/Bax balance and PARP-1 cleavage through the ERK signaling pathway.

To investigate the expression profile of interleukin-1β (IL-1β) in osteosarcoma tissues, explore its correlation with clinical prognosis, and to elucidate the underlying molecular mechanisms of IL-1β regulating the proliferation of osteosarcoma cells.

Four osteosarcoma patients admitted to Department of Orthopedics of our hospital from December 2020 to January 2024 were enrolled, and their tumor and adjacent tissues were collected to detect differential mRNA and protein expression of IL-1β by immunohistochemistry, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), and Western blotting. Additionally, 15 paraffin-embedded osteosarcoma specimens collected between March 2018 and August 2021 were immunohistochemically stained and scored using ImageJ, and then divided into high IL-1β expression group (3+, 2+) and low expression group (1+, 0). Kaplan-Meier analysis was used to determine the association between the scoring results and patient survival rates. In in vitro experiments, osteosarcoma cell line U2OS was subjected and treated with 0 to 100 ng/mL recombinant IL-1β protein. EdU incorporation assay, flow cytometry, CCK-8 assay and colony formation assay were performed to screen the optimal proliferation-stimulating concentration. Transcriptome sequencing was carried out on the U2OS cells with 40 ng/mL IL-1β treatment and untreated cells to analyze significantly up-regulated signals involved in regulating U2OS proliferation. The obtained key regulatory molecule, nuclear factor kappa B (NF-κB) was then verified by RT-qPCR, Western blotting, and immunofluorescence staining. After IL-1 receptor type 1 (IL-1R1) was knocked down by lentiviral transfection, or the cells were treated with NF-κB inhibitor embelin, the changes in cell proliferation were detected with EdU incorporation assay, flow cytometry, CCK-8 assay, and colony formation assay. In in vivo experiments, 12 female nude mice (5 weeks old) were randomly divided into control group, IL-1R1 knockdown group, and IL-1R1 inhibitor (anakinra) injection group, with 4 animals in each group. An orthotopic osteosarcoma model was established by intratibial injection, and tumor growth was compared across groups.

Immunohistochemical staining and survival analysis demonstrated that osteosarcoma patients with high IL-1β expression level had poorer prognosis (P<0.05). In vitro experiments showed that IL-1β treatment significantly increased the EdU incorporation rate (P<0.05), enhanced G2/M cell cycle arrest (P<0.05), and improved the colony formation ability (P<0.05) in U2OS cells, indicating that IL-1β promotes osteosarcoma cell proliferation. Transcriptome data analysis revealed 4 165 differentially expressed genes (1 688 up-regulated and 2 477 down-regulated) between IL-1β-treated and untreated U2OS cells. IL-1β treatment obviously promoted cell cycle and up-regulated the proteins related to NF-κB signaling pathway in U2OS cells. RT-qPCR confirmed the mRNA levels of cell cycle-related molecules were enhanced by IL-1β treatment, which was further confirmed by Western blotting at protein level. IL-1R1 knockdown resulted in notably decreased proliferation ability in U2OS cells compared with the control cells (P<0.05). Both RT-qPCR and Western blotting confirmed that IL-1R1 knockdown reduced the expression levels of cell cycle-related proteins and NF-κB. Addition of NF-κB inhibitor, embelin, significantly inhibited the IL-1β-induced EdU incorporation rate (P<0.05), G2/M phase arrest (P<0.05), and colony formation ability (P<0.05) in U2OS cells, and suppressed the expression of cell cycle-related proteins. In vivo experimental results showed that the tumor weight in the IL-1R1 knockdown group (0.75±0.10 g) and anakinra injection group (0.93±0.06 g) was statistically lower than that in the control group (1.46±0.09 g) (both P<0.05).

Intratumoral IL-1β level is positively correlated with poor prognosis in osteosarcoma patients. IL-1β promotes the proliferation ability of osteosarcoma cells through the IL-1R1/NF-κB signaling axis.

To investigate the impact of propofol-based total intravenous anesthesia(TIVA) versus sevoflurane-propofol intravenous-inhalation combined anesthesia(IICA) on 5-year postoperative survival rates in patients undergoing radical hepatectomy for hepatocellular carcinoma(HCC).

A retrospective cohort study was conducted on the clinical and follow-up data from 504 patients undergoing radical HCC surgery in our hospital between January 2015 and December 2017. According to different anesthesia techniques, the patients were divided into a IICA groups(n=176) and a TIVA group(n=328). The 5-year postoperative survival rates were compared between the 2 groups of patients. Stratified analyses were carried out by age, tumor size and number, Child-Pugh class and model for end-stage liver disease(MELD) score, presence of portal vein tumor thrombus(PVTT), intraoperative transfusion, hepatitis B surface antigen status, alpha-fetoprotein(AFP), tumor node metastasis(TNM) stage, and Barcelona clinic liver cancer(BCLC) stage to compare the impact of the 2 anesthesia methods on postoperative survival rates in subgroups.

Among the cohort, the median 5-year survival was 33.00(14.25 to 60.00) months in the TIVA group with 212 deaths(64.60%), and 27.00(11.00 to 60.00) months in the IICA group with 125 deaths(71.00%). There was no statistically significant difference in 5-year survival rate between groups(HR=1.27, 95%CI: 0.96 to 1.67, P>0.05). Stratified analysis revealed significant increased 5-year mortality risk with CIVA in subgroups with MELD score >7.24(HR=1.61, 95%CI: 1.11 to 2.32, P=0.011), BCLC stage B(HR=1.74, 95%CI: 1.11 to 2.71, P=0.015), absence of PVTT(HR=1.35, 95%CI: 1.04 to 1.74, P=0.026), and no intraoperative transfusion(HR=1.34, 95%CI: 1.02 to 1.75, P=0.034).

Among patients undergoing radical hepatectomy for HCC, there is no difference in 5-year overall survival between propofol-based TIVA and sevoflurane-propofol IICA. However, IICA is associated with significantly increased 5-year mortality risk in specific subgroups: MELD score >7.24, absence of PVTT, BCLC stage B, and no intraoperative transfusion.

To assess the predictive value of the pan-immune-inflammation value(PIV) for all-cause and cause-specific mortality among individuals with depressive symptoms.

This prospective cohort study utilized data from the US National Health and Nutrition Examination Survey(NHANES, 2005 to 2018) and the National Death Index(NDI, 2005 to 2019). A total of 8 567 American patients with depression were enrolled. Participants were grouped by PIV quartiles(Q1, Q2, Q3, Q4) or dichotomized(low group, high group). Cox proportional hazards models were employed to estimate the association between PIV and all-cause, cardiovascular, and cancer mortality in patients with depression. Smooth curve fitting was applied to explore potential non-linear dose-response relationships. Threshold effect analysis was conducted to identify an inflection point, upon which a two-piecewise regression model was constructed. Kaplan-Meier survival curves were plotted to examine the association between PIV levels and survival status. Subgroup analyses were performed to evaluate the robustness of the observed associations.

Cox regression showed that higher PIV levels were significantly associated with increased risks of all-cause mortality(HR=1.05, 95%CI: 1.04 to 1.07, P<0.001), cardiovascular mortality(HR=1.07, 95%CI: 1.05 to 1.10, P<0.001), and cancer mortality(HR=1.05, 95%CI: 1.01 to 1.08, P<0.001). Smooth curve fitting revealed a U-shaped relationship between PIV and all-cause mortality, with an inflection point at 80.97(P<0.05). Survival analysis indicated that when PIV>80.97, compared with the low group, the high group had increased all-cause mortality(HR=1.29, 95%CI: 1.12 to 1.48, P<0.001); compared with the Q1 group, the Q4 group also showed increased all-cause mortality(HR=1.53, 95%CI: 1.25 to 1.87, P<0.001). Subgroup analyses revealed stronger associations in specific populations: among females, for all-cause mortality(HR=1.08, 95%CI: 1.05 to 1.10, P=0.038) and cardiovascular mortality(HR=1.11, 95%CI: 1.07 to 1.16, P=0.031); In individuals with diabetes and those of other races(excluding Mexican American, other Hispanic, non-Hispanic White, and non-Hispanic Black), stronger associations were found between PIV and all-cause mortality (diabetes: HR=1.09, 95%CI: 1.06 to 1.10, P=0.023; other races: HR=1.22, 95%CI: 1.11 to 1.35, P=0.032) and cancer mortality (diabetes: HR=1.12, 95%CI: 1.06 to 1.18, P=0.006; other races: HR=2.00, 95%CI: 1.79 to 2.24, P=0.002).

Elevated PIV serves as an independent risk factor for multiple mortality outcomes in individuals with depressive symptoms. This study underscores the potential of PIV as a biomarker for predicting mortality risk. Utilizing PIV could aid in the early identification and targeted management of high-risk individuals, contributing to a comprehensive strategy for reducing the disease burden.