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 systematically investigate the bidirectional causal relationship between 10 uremia-related toxins and metabolites and CD8⁺ T cell senescence phenotypes using Mendelian randomization (MR).

A bidirectional MR analysis was performed using genome-wide association studies (GWAS) data to extract single nucleotide polymorphisms closely associated with 10 uremia-related toxins and metabolites and CD8⁺ T cell senescence phenotypes as instrumental variables. The primary analytical method was inverse variance weighting (IVW), supplemented by MR-Egger, weighted median, simple mode, and weighted mode. The robustness and potential pleiotropy of the results were verified by sensitivity analyses including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out analysis.

MR analysis showed that carnitine level was positively associated with the proportion of terminally differentiated CD8⁺ T cells (IVW: β=1.71, 95%CI: 0.59 to 2.83, P=0.003), the proportion of CD45RA⁺CD28^⁻CD8⁺T cells (IVW: β=2.23, 95%CI: 0.65 to 3.80, P=0.006), and the proportion of CD28^⁻CD8⁺T cells (IVW: β=1.13, 95%CI: 0.11 to 2.15, P=0.030). Kynurenine level also showed a significant positive association with the proportion of terminally differentiated CD8⁺T cells (IVW: β=1.69, 95%CI: 0.57 to 2.82, P=0.000 3), while IL-6 level presented a positive correlation with the proportion of CD28^⁻CD8⁺T cells (IVW: β=0.28, 95%CI: 0.03 to 0.53, P=0.026) and the proportion of CD45RA⁺CD28^⁻CD8⁺T cells (IVW: β=0.41, 95%CI: 0.02 to 0.79, P=0.04). N²,N²-dimethylguanosine level was positively correlated with CD45RA⁺CD28^⁻CD8⁺T cell absolute count (IVW: β=2.53, 95%CI: 0.51 to 4.55, P=0.014). Reverse MR analysis revealed an increase in the absolute count of CD45RA⁺CD28^⁻CD8⁺T cells was causally associated with a reduction in carnitine levels (IVW: β=-0.000 03, 95%CI: -0.000 062 to 0.000 004, P=0.024). All sensitivity analyses supported the robustness of the main findings.

There are bidirectional causal associations between uremia-related toxins and metabolites and CD8⁺T cell senescence, providing novel causal insights and potential intervention targets for immune dysfunction in uremic patients.

To investigate whether icariin (ICA) ameliorates cognitive impairment and modulates relevant endocrine hormone alterations in Alzheimer’s disease (AD) model mice by regulating osteocalcin (OCN) secretion.

An AD mouse model was established by intraventricular injection of okadaic acid (OA). Using a stratified design, 4-week-old male SPF mice (weighing 18 to 22 g) were randomly divided into 8 groups (n=6): wild-type (WT) control group (intragastric administration of 60 mg/kg normal saline); WT-AD group (WT mice with left intracerebroventricular injection of 1 µL OA); WT+ICA group (60 mg/kg ICA daily); WT-AD+ICA group (WT-AD mice with daily 60 mg/kg ICA); OCN^-/- control group (OCN^-/- mice with 60 mg/kg normal saline); OCN^-/--AD group (OCN^-/- mice with left intracerebroventricular injection of 1 µL OA); OCN^-/-+ICA group (OCN^-/- mice with 60 mg/kg ICA daily); and OCN^-/--AD+ICA group (OCN^-/--AD mice with 60 mg/kg ICA daily). The Morris water maze test was conducted to assess learning and memory abilities, while open field test was performed to evaluate anxiety levels. Hippocampal histopathological changes were observed with HE staining and silver impregnation staining; Nissl bodies in hippocampal neurons were detected with Nissl staining. Immunohistochemistry assay was employed to determine the expression of amyloid β-protein (Aβ) and OCN, and Western blotting was used to measure the protein levels of Aβ and OCN. ELISA was applied to detect the expression levels of corticotropin-releasing hormone (CRH), glucose (GLU), glucocorticoid (GC), and cortisol (COR).

Morris water maze test demonstrated that compared with the WT-AD group, the WT-AD+ICA group exhibited significantly shortened escape latency, prolonged time spent in the target quadrant, and increased platform crossing frequency (all P<0.05); similarly, the OCN^-/--AD+ICA group showed improvements than the OCN-/--AD group (all P<0.05). Open field test results indicated that compared with the WT-AD group, the WT-AD+ICA group displayed significantly increased total exploration distance, distance in the center, and time in the center, enhanced activity willingness, and reduced time in peripheral zone and distance in peripheral zone (all P<0.05); similar improvements were observed in the OCN^-/--AD+ICA group compared with the OCN^-/--AD group (all P<0.05). Staining results revealed that ICA intervention attenuated hippocampal pathology, restored hippocampal morphological architecture, reduced neurofibrillary tangles (NFTs), and promoted gradual recovery of Nissl bodies; however, the OCN^-/- mice failed to achieve complete normalization. Immunohistochemistry assay showed that compared with the WT-AD group, the WT-AD+ICA group exhibited decreased Aβ levels and increased OCN levels (all P<0.05); similar trends were observed in the OCN^-/--AD+ICA group relative to the OCN^-/--AD group (all P<0.05). Western blotting demonstrated that compared with the WT-AD group, the WT-AD+ICA group showed reduced Aβ expression and elevated OCN expression (both P<0.05); comparable changes were found in the OCN^-/--AD+ICA group compared with the OCN^-/--AD group (both P<0.05). ELISA indicated that compared with the WT-AD group, the WT-AD+ICA group exhibited significantly decreased levels of CRH, GLU, GC, and COR (all P<0.05); similar reductions were observed in the OCN^-/--AD+ICA group compared with the OCN^-/--AD group (all P<0.05).

ICA ameliorates cognitive impairment and reduces levels of related hyperactive endocrine hormones in AD model mice through regulating OCN secretion.

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 analyze the differential expression profiles of small nucleolar RNAs (snoRNAs) in lung adenocarcinoma and their association with prognosis, screen and validate lung adenocarcinoma-related snoRNAs, and explore their roles in tumorigenesis and progression.

Differentially expressed snoRNAs between lung adenocarcinoma and normal tissues were screened using Arraystar Small RNA expression microarrays. The obtained candidates were validated through the GEO database (GSE261702), followed by selecting snoRNAs that passed molecular cloning experiments, and finally RT-qPCR. By constructing SCARNA4 overexpression models (Vector group and SCARNA4 group) and knockdown models (siNC group and siSCARNA4 group), proliferation, migration and invasion assays were carried out to assess the biological functions of SCARNA4 in lung adenocarcinoma cells. Based on tumor tissues from 108 lung adenocarcinoma patients (Second Affiliated Hospital of Army Medical University, between February 2013 and May 2015), the expression level of SCARNA4 was detected by RT-qPCR. Using X-tile software to determine the optimal cut-off value (3.48), the patients were accordingly stratified into high (57 cases) and low SCARNA4 expression (51 cases) groups. Kaplan-Meier survival curves and Cox proportional hazards regression models were constructed to analyze the impact of SCARNA4 expression on prognosis.

Small RNA microarray identified 62 up-regulated and 4 down-regulated snoRNAs in lung adenocarcinoma tissues. Integration with GEO database and molecular cloning yielded 8 candidate snoRNAs. RT-qPCR results revealed significantly elevated SCARNA4 expression in lung adenocarcinoma tissues than normal tissues (P=0.042 7). Overexpression of SCARNA4 significantly promoted the proliferative, migrative, and invasive capacities in A549 cells (P<0.01), whereas its knockdown obviously inhibited these functions (P<0.01). Kaplan-Meier survival analysis demonstrated significantly shorter overall survival in the high-expression group when compared with the low-expression group (P=0.034). Univariate Cox regression analysis further confirmed that high SCARNA4 expression was significantly associated with poor prognosis (HR=2.285, 95%CI: 1.040 to 5.020, P=0.039). Multivariate Cox regression analysis confirmed that, after adjusting for relevant covariates, the expression level of SCARNA4 was an independent risk factor of overall survival of lung adenocarcinoma patients, and its high expression was notably associated with shortened overall survival of patients (HR=3.038, 95%CI:1.261 to 7.323, P=0.013).

SCARNA4 is up-regulated in lung adenocarcinoma tissues and associated with poor prognosis. It may be involved in the tumorigenesis and development of lung adenocarcinoma by regulating cell proliferation, migration, and invasion. The molecule might hold promise as a novel therapeutic target and prognostic biomarker for lung adenocarcinoma.

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 investigate the independent influencing factors for delayed discharge from the post-anesthesia care unit (PACU) in elderly patients undergoing non-cardiac surgery under general anesthesia, encompassing preoperative status, intraoperative management, and innovative circadian rhythm dimensions, to provide references for optimizing perioperative management.

This study adopted a retrospective case-control design. A total of 1 469 elderly patients (aged≥60 years) who underwent non-cardiac surgery under general anesthesia and were admitted to the PACU for recovery at our department between January 2021 and December 2023 were enrolled. Based on whether the time from PACU admission to achieving a modified Aldrete score≥9 exceeded 120 min, patients were divided into a delayed group (n=709) and a non-delayed group (n=760). Data on demographic characteristics, preoperative comorbidities, American Society of Anesthesiologists (ASA) physical status classification, intraoperative management indicators, postoperative monitoring indicators, PACU admission-related indicators and surgery/PACU admission time rhythm data were collected via the Hospital Inpatient Management System and the Anesthesia Clinical Information System. Univariate comparisons of various indicators between the 2 groups were performed using the Chi-square test or binary logistic regression. Subsequently, variables with P<0.05 in the univariate analysis were included in a binary logistic stepwise regression model to analyze the independent factors influencing delayed PACU discharge.

Univariate analysis showed that the delayed group had significantly higher rates of male sex, ASA class Ⅲ-Ⅳ, preoperative respiratory disease, intraoperative use of vasoactive drugs and colloids, total intraoperative fluid intake and output, intraoperative blood loss, postoperative use of intravenous and nerve block analgesia, surgery and anesthesia duration, and body temperature upon PACU admission compared to the non-delayed group (P<0.05). Conversely, the delayed group had a significantly lower rate of using the neuromuscular reversal agent neostigmine and lower postoperative hemoglobin levels (P<0.05). Regarding circadian rhythm, significant differences were found between the 2 groups in the distribution of surgery start time and PACU admission time (P<0.001). Multivariate analysis revealed that preoperative respiratory disease (β=0.616, P<0.001), ASA class Ⅲ-Ⅳ(β=0.501, P=0.002), intraoperative colloid use (β=0.626, P<0.001), increased total intraoperative fluid intake (β=0.001, P<0.001), surgery initiation during the Si period (9:00-11:00) (β=0.353, P=0.005), and PACU admission during the Shen period (15:00-17:00) (β=0.660, P<0.001) were independent risk factors for delayed discharge. In contrast, the use of the neuromuscular reversal agent neostigmine (β=-0.327, P=0.007) and PACU admission during the Xu period (19:00-21:00) (β=-0.468, P=0.042) were independent protective factors.

Delayed discharge from the PACU after general anesthesia in elderly patients is jointly influenced by multiple factors, including preoperative patient status, intraoperative management, recovery-phase interventions, and surgical timing rhythm. Implementing individualized anesthesia and fluid management for high-risk elderly patients, using neuromuscular reversal agents, and considering the time rhythm effects in surgical scheduling and PACU resource allocation may reduce the incidence of delayed PACU discharge after general anesthesia.

To analyze the incidence and related risk factors of postoperative pneumonia(POP) in patients with acute type A aortic dissection(ATAAD) after surgery.

A multi-hospital retrospective cohort study was conducted, consecutively enrolling 493 ATAAD patients who underwent surgical treatment at the Second Affiliated Hospital of Army Medical University, Affiliated Hospital of Southwest Medical University, and Chongqing Emergency Medical Center between January 2018 and December 2022. Clinical data were collected, including general characteristics, preoperative comorbidities, surgical indicators, and postoperative monitoring parameters. The participants were divided into a POP group (n=138) and a control group (n=355) based on POP occurrence. Univariate analysis was used to screen the risk variables related to the occurrence of POP(P<0.15), followed by multivariate logistic regression using forward, backward, and enter methods to identify the independent risk factors. Receiver operating characteristic(ROC) curve analysis was used to assess the predictive efficacy of continuous variables and determine optimal cut-off values.

Among the 493 patients, the incidence of POP was 28.0%(138/493). The POP group exhibited significantly prolonged postoperative mechanical ventilation time(92.6±68.5 vs 45.3±32.8 h, P<0.001), length of intensive care unit(ICU) stay(156.8±88.3 vs 102.5±65.7 h, P<0.001), and length of total hospitalization stay(27.3±14.6 vs 19.8±10.2 d, P<0.001), along with significantly higher in-hospital mortality(18.8% vs 7.9%, P<0.001) when compared with the control group. Multivariate logistic regression analysis identified preoperative chronic obstructive pulmonary disease(COPD)(OR=2.447, 95%CI: 1.191 to 5.026, P=0.015), history of aspiration pneumonia(OR=2.282, 95%CI: 0.992 to 5.246, P=0.052), mechanical ventilation duration ≥68 h(OR=3.619, 95%CI: 1.963 to 6.672, P<0.001), red blood cell transfusion volume≥10 U(OR=1.984, 95%CI: 1.113 to 3.536, P=0.020), intraoperative peak blood glucose ≥11 mmol/L(OR=2.134, 95%CI: 1.190 to 3.826, P=0.011), and postoperative 24 h total drainage ≥1 100 mL(OR=1.808, 95%CI: 1.032 to 3.169, P=0.039) as independent risk factors for POP in ATAAD patients. ROC curve analysis further validated the predictive efficacy of these continuous variables, with mechanical ventilation duration demonstrating an AUC value of 0.762(95%CI: 0.718 to 0.806), red blood cell transfusion a value of 0.682(95%CI: 0.632 to 0.732), intraoperative peak blood glucose a value of 0.658(95%CI: 0.606 to 0.710), and postoperative 24 h drainage a value of 0.642(95%CI: 0.589 to 0.695).

The incidence of POP in ATAAD patients is as high as 28.0%, significantly increasing the mortality and hospital stay. Individualized preventive strategies targeting preoperative COPD, aspiration pneumonia history, prolonged mechanical ventilation, massive red blood cell transfusion, intraoperative hyperglycemia, and early postoperative high-volume drainage may reduce the incidence of POP and improve the prognosis of patients.

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.

To analyze long-term trends in the burden of major depressive disorder(MDD) in China and globally from 1990 to 2023 based on the Global Burden of Disease 2023(GBD 2023), characterize pre- and post-pandemic patterns and demographic drivers, and project future burden trends.

Data were extracted from the GBD 2023 database covering 204 countries/territories. Age-standardized incidence rate(ASIR), age-standardized prevalence rate(ASPR), age-standardized disability-adjusted life year rate(ASDR), and their 95% uncertainty intervals(UI) were calculated. Joinpoint regression analysis was used to estimate average annual percent change(AAPC) with 95% confidence intervals(CI), along with correlations with sociodemographic index(SDI), inequality, and frontier gaps. Das Gupta decomposition was applied to assess demographic contributions. Autoregressive integrated moving average(ARIMA) models were developed based on 1990 to 2018 time-series to forecast trends from 2024 to 2040. Attributable burdens of major modifiable social risk factors were also analyzed.

In 2023, China’s ASIR, ASPR, and ASDR were 3 002.50/100 000, 2 107.50/100 000, and 429.44/100 000, respectively, all lower than the global estimates of 3 464.17/100 000, 2 815.75/100 000, and 567.77/100 000, correspondingly. From 1990 to 2023, all 3 age-standardized rates showed upward trends. In China, AAPC was 1.214%(P<0.05) for ASIR, 0.920%(P<0.05) for ASPR, and 0.947%(P<0.05) for ASDR; globally, corresponding AAPCs were 1.222%(P<0.05), 1.385%(P<0.05), and 1.380%(P<0.05), respectively. Post-pandemic ASPR and ASDR maintained high plateau levels: in 2023, China’s rate increased by 7.5% and 7.4% relative to 2019, while global rates increased by 24.5% and 24.1%, respectively. Age distribution patterns showed that in 2023, China’s crude incidence rate peaked at 3 909.88/100 000(95%UI: 3 009.15 to 4 874.13) in the 15 to 19 years age group, and crude DALY rate also peaked at 584.29/100 000(95%UI: 361.23 to 887.27) in the same age group. Whereas the crude prevalence rate increased with age and peaked at age of ≥95 years at 3 084.41/100 000(2 410.08 to 4 107.62). In 2023, correlations between ASIR/ASPR/ASDR and SDI were weak and not statistically significant(P>0.05). ARIMA projections suggested that by 2040, China’s ASIR, ASPR, and ASDR would reach 3 648.92/100 000, 2 576.16/100 000, and 536.31/100 000, respectively. In 2023, attributable proportions of DALYs(China/global) were 8.70%/8.32% for intimate partner violence, 8.24%/6.82% for bullying victimization, and 7.48%/8.20% for childhood sexual abuse. Sex-stratified analyses consistently showed higher burdens in females than in males.

From 1990 to 2023, the burden of MDD in China and globally continued to rise. The COVID-19 pandemic produced an additional surge, with accumulated burden maintaining high levels post-pandemic. Age patterns indicate coexistence of “high incidence and high health loss in adolescence” and “accumulation of absolute burden in middle-aged and older adults.” Projections based on pre-pandemic trends suggest that China’s future burden may continue to increase. Countermeasures While improving service accessibility, we recommend advancing screening and stratified interventions to priority populations, especially adolescents and females, and integrating social risk governance measures, such as anti-domestic violence, anti-bullying, and child protection, into a comprehensive MDD prevention and control system.

To explore the dynamic developmental trajectory of depressive symptoms among middle-aged and older adults in China, and to analyze the influences of childhood trauma and cognitive function on the trajectory.

Based on data from the China Health and Retirement Longitudinal Study from 2011 to 2020, a prospective cohort study was conducted on 7 916 middle-aged and older adults across 5 waves of surveys (T1=2011, T2=2013, T3=2015, T4=2018, T5=2020). Childhood trauma questionnaire, cognitive function questionnaire, and Center for Epidemiologic Studies Depression Scale were used to measure the experience of childhood trauma, cognitive function level, and depression level respectively. Pearson correlation analysis was employed to explore the correlations among variables. A latent growth curve model was constructed, and the fit of the model was evaluated based on indicators such as comparative fit index (CFI), Tucker-Lewis index (TLI), standardized root mean square residual (SRMR), and root mean square error of approximation (RMSEA). The nonlinear characteristics of the developmental trajectory of depression were depicted through intercept (I), slope (S), and quadratic slope (Q) parameters. The regression coefficient (β) and its 95% confidence interval (CI) were estimated using the Bootstrap method to explore the influencing factors of the developmental trajectory of depression in middle-aged and older adults.

① Childhood trauma was significantly positively correlated with cognitive function at each time point (r=0.044 to 0.077, P<0.001), and with depression at each time point (r=0.057 to 0.095, P<0.001). Cognitive function was significantly negatively correlated with depression at each time point (r=-0.257 to -0.133, P<0.001). ② Quadratic growth model demonstrated good fit (CFI=0.997, TFI=0.995, SRMR=0.017, RMSEA=0.029). Depressive symptoms exhibited a quadratic growth trend of “decreasing first, then increasing” over time (I=8.067, S=-0.158, Q=0.033, P<0.001). ③ After incorporating the variable of childhood trauma, childhood trauma significantly positively predicted the initial level of depression (β=0.294, 95%CI: 0.208 to 0.381, P<0.001), but had no significant predictive effect on the linear slope or quadratic slope. ④After further incorporating the cognitive function variable, the cognitive function at each of the 5 time points could significantly negatively predict the depression at the same time period (TI: β=-0.194, 95%CI: -0.233 to -0.155; T2: β=-0.135, 95%CI: -0.161 to -0.109; T3: β=-0.131, 95%CI:-0.161 to -0.100; T4: β=-0.134, 95%CI: -0.163 to -0.106; T5: β=-0.177, 95%CI:-0.220 to -0.134; all P<0.001).

The development trajectory of depression among middle-aged and older adults displays a nonlinear trend of quadratic growth. Childhood trauma is a risk factor for the initial level of depression in them, while cognitive function serves as a protective factor for the developmental trajectory of depression.

To revise and validate the Obedience Attitude Questionnaire for College Students (OAQ-CS), explore the sociological characteristics of obedience attitude, and preliminarily investigate the impact of obedience attitude on creativity.

Based on WANG Yuchao’s 8-item obedience questionnaire, the revision was made according to the characteristics of college students. A cross-sectional observation was conducted on 4 200 college students subjected with stratified cluster sampling from 3 institutions in Chongqing (Army Medical University, Chongqing University of Education, and Chongqing University). The participants were surveyed with the OAQ-CS and the College Students’ Creativity Assessment Inventory (CSCAI). The obtained data were analyzed with item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability testing. Mann-Whitney U nonparametric test was used to observe the demographic differences of college students’ obedience attitudes, Spearman correlation analysis was explored to analyze the correlation between variables, and stratified linear regression analysis was performed to explore the predictive factors of obedience attitude and creativity.

① Item analysis revealed no items requiring deletion. EFA extracted 2 factors: self-interested obedience and harm-avoidance obedience. CFA demonstrated good model fit (χ²/df=2.90, RMSEA=0.03, CFI=0.99, IFI=0.99, TLI=0.99). The scale exhibited strong internal consistency reliability (α=0.87 to 0.91). ② College students had high overall propensity for obedience (42.51±9.85, M=46), with harm-avoidance obedience score (21.34±5.48) higher than self-interested obedience score (21.17±5.34). Total obedience attitude and its dimensions showed significant positive correlations with creativity (r_s=0.28 to 0.87, P<0.001). Males and the individuals aged ≤22 years scored higher than their counterparts in females and those aged >22 years individuals in both obedience attitude and its dimensions(all P<0.05). Age (β=-0.21, P<0.001) was a negative predictor of obedience attitude, while male (β=0.06, P<0.001), married (β=0.11, P<0.001), and graduate students (β=0.13, all P<0.001) were positive predictors. Male (β=0.04, P<0.01), graduate students (β=0.05, P<0.05), obedience attitude (β=0.44, P<0.001), and the interaction term between obedience attitude and age (β=0.05, P<0.05) positively predicted creativity, whereas the interaction term between obedience attitude and marital status (β=-0.04, P<0.05) was a negative predictor of creativity.

Our revised OAQ-CS has good reliability and validity. College students display a high obedience tendency. Older individuals exhibit lower obedience and males higher than females. Moderate obedience, encompassing both self-interested and harm-avoidance dimensions, is conducive to creativity enhancement.

To characterize the myocardial proteomic and metabolomic alterations induced by high-altitude exposure and hemorrhagic shock (HS) under hypobaric hypoxic conditions, and to evaluate the regulatory effects of early lactated Ringer’s (LR) resuscitation on related molecular abnormalities, providing evidence for elucidating the mechanisms of myocardial injury in high-altitude HS and optimizing resuscitation strategies in such conditions.

Forty SPF-grade male SD rats (10 to 12 weeks old, weighing 180 to 220 g) were randomly divided into a normoxic control group (NC), a high-altitude sham group (Sham), a high-altitude uncontrolled HS (UHS) and a high-altitude HS with LR resuscitation group (LR1h), with 10 animals in each group. Hypobaric hypoxic condition was induced by rats placed in a hypobaric chamber to simulate an altitude of 5 000 m for 48 h. After chamber exit, the rats received an injection of oleic acid via the tail vein for 0.5 h, followed by splenic artery transection to induce uncontrolled hemorrhage until the mean arterial pressure (MAP) decreased to 40 mmHg. Thus, a high-altitude HS model was established. After successful modeling, the UHS group received no resuscitation with continuous monitoring only, while the LR1h group received an infusion of LR solution via the femoral vein for 1 h resuscitation under hypobaric condition. At designated time points, heart tissues were collected for 4D-FastDIA quantitative proteomics (n=4) and untargeted metabolomics analysis (n=6). Principal component analysis (PCA), differential protein/metabolite screening, and gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to characterize myocardial molecular expression profiles under different treatment conditions.

High-altitude exposure effect (Sham vs NC): totally 229 differentially expressed proteins (DEPs) were identified (154 up-regulated and 75 down-regulated, P<0.05). Enrichment analyses showed up-regulation of immune and inflammatory response-related processes, and downregulation of cardiac contraction, mitochondrial gene expression, and protein synthesis. There were 633 differential metabolites identified (509 up-regulated and 124 down-regulated, VIP≥1, P<0.05), primarily enriched in fundamental metabolic pathways, such as lipid, terpenoid/polyketide, and amino acid metabolic pathways. HS shock effect (UHS vs Sham): A total of 193 DEPs were identified (42 up-regulated and 151 down-regulated, P<0.05), characterized by enhanced cholesterol and lipid metabolism, whereas global down-regulation of complement-coagulation cascades, lysosomal function, immune and inflammatory regulation, and multiple infection-related pathways. Among the 1 100 identified differential metabolites, there were 267 up-regulated and 833 down-regulated (VIP≥1, P<0.05). The types of enriched pathways were generally consistent, but the overall number of enriched compounds was decreased, with more pronounced reductions in key metabolic axes, including lipid metabolism (from 31 to 20), terpenoid/polyketide metabolism (from 20 to 14), and amino acid metabolism (from 11 to 6). LR resuscitation effect (LR1h vs UHS): A total of 108 DEPs were identified (39 up-regulated and 69 down-regulated, P<0.05). Vesicular transport, autophagy, and renin-angiotensin system pathways were up-regulated, but complement-coagulation cascade, humoral immunity, inflammatory response, and multiple infection- and metabolism-related pathways remained down-regulated, along with suppression of oxygen transport processes. Totally 494 differential metabolites were identified (456 up-regulated and 38 down-regulated, VIP≥1, P<0.05). Enriched pathways remained concentrated in the above main metabolic routes, but the number of enriched compounds in these pathways further decreased compared with the shock state, including lipid metabolism (from 20 to 10), terpenoid/polyketide metabolism (from 14 to 12), and amino acid metabolism (from 6 to 0).

Under high-altitude hypobaric hypoxia, HS induces myocardial immune/coagulation suppression and metabolic disorder. Early resuscitation with LR solution fails to reverse these molecular alterations, indicating that simple crystalloid volume resuscitation is insufficient to protect the myocardium in high-altitude hemorrhagic shock.