Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Alcoholic liver fibrosis is a critical step in the progression of alcoholic liver disease toward liver cirrhosis， yet there is currently still a lack of effective and specific anti-fibrotic therapeutic strategies. Recent studies have shown that as an iron-dependent， lipid peroxidation-driven form of regulated cell death， ferroptosis plays an important role in alcohol-related hepatocellular injury and fibrogenesis. Reactive oxygen species generated during alcohol metabolism can damage hepatocytes， impair their antioxidant defense ability， and lead to disruption of iron homeostasis and accumulation of lipid peroxides， ultimately triggering ferroptosis. Hepatocyte ferroptosis can promote fibrosis by amplifying inflammatory responses and activating hepatic stellate cells， whereas selective induction of ferroptosis in activated hepatic stellate cells may attenuate fibrosis， highlighting the “double-edged sword” effect of ferroptosis. Current interventions against ferroptosis mainly focus on applying antioxidant approaches， reducing iron burden， or blocking the amplification of lipid peroxidation， which have shown preliminary efficacy and a potential clinical value， but there are still limitations such as single-target actions and insufficient cell selectivity. In the future， nanotechnology-based delivery and other targeting strategies may help to realize multi-pathway coordination and cell-specific modulation， thereby improving the anti-fibrotic efficacy of ferroptosis-oriented therapies.

Objective:To evaluate the accuracy and safety profile of a novel cuboid orientation-guided frontal horn ventriculostomy technique in patients with large hemispheric infarction (LHI).Methods:It was conducted a retrospective cohort study of 48 consecutive LHI patients who underwent the innovative ventriculostomy procedure between time period. Primary outcomes included procedural accuracy (success rates, catheter positioning) and safety indicators (complication rates).Results:All the punctured ventricles were small or of normal size. The success rate of puncture was 100%, the success rate of one-time puncture was 87% (42/48), and the average number of puncture was 1.13 times per case. The ratio of well-positioned tube heads was 87.5% (42/48). The actual angle of the inward deviation of the puncture ranged from -2o to 5o, with an average of 0o±0.3o. The depth of puncture was 7.0-8.0 cm ( 7.3±0.3) cm. The incidence of bleeding around the puncture path was 1.3% (2/48 ) and no massive bleeding occurred. At the 6-month follow-up, one case (2.94%) among the 34 survivors had epilepsy.Conclusions:The cuboid orientation-guided frontal horn ventriculostomy technique demonstrates exceptional procedural accuracy and an excellent safety profile in LHI patients, with high first-pass success rates (87.5%) and minimal complications (4.2% minor hemorrhage). These findings support its clinical adoption for this patient population.

Objective:To explore the impact of adolescent mental health status on smartphone addiction, and construct a predictive model for smartphone addiction based on the eXtreme Gradient Boosting(XGBoost) algorithm and multivariate Logistic regression.Methods:In April 2023, a cross-sectional survey was conducted among 14 666 adolescents.All participants were systematically evaluated using a self-developed general information questionnaire, the middle school student mental health scale(MSSMHS), the adolescents self-harm scale(ASHS), the interaction anxiousness scale(IAS), the mobile phone addiction index(MPAI), the middle school students shame scale(MSSS), the UCLA loneliness scale(UCLA-LS), the multidimensional peer victimization scale(MPVS), and the basic psychological needs scale(BPNS).R software version 4.3.2 was used for data analysis. Participants were randomly divided into training set and validation set at the ratio of 7∶3.The XGBoost model and multivariate logistic regression model were constructed to predict the risk of smartphone addiction, and a nomogram was plotted.Model performance was evaluated using the Hosmer-Lemeshow test, area under the curve(AUC), and accuracy(ACC).Results:(1) A total of 14 036 high school students were included in the study, with 5 069(36.1%) exhibited smartphone addiction.The training set comprised 9 826 students, with 3 549(36.1%) being smartphone addicts.The validation set included 4 210 students, with 1 520(36.1%) being smartphone addicts.(2) The XGBoost model identified shame-proneness and social anxiety as the two main predictors of smartphone addiction.(3) Multivariate Logistic regression analysis revealed that anxiety( B=0.328, OR(95% CI)=1.39(1.07-1.81), P=0.015), interpersonal sensitivity( B=0.311, OR(95% CI)=1.36(1.05-1.77), P=0.018), learning pressure( B=0.606, OR(95% CI)=1.83(1.46-2.31), P<0.001), mood swings( B=0.775, OR(95% CI)=2.17(1.70-2.78), P<0.001), social anxiety( B=0.024, OR(95% CI)=1.02(1.01-1.04), P<0.001), shame-proneness( B=0.049, OR(95% CI)=1.05(1.04-1.06), P<0.001), and peer victimization( B=0.037, OR(95% CI)=1.04(1.02-1.06), P<0.001) were significant predictors of smartphone addiction.(4) The ACC and AUC values of the XGBoost model were 0.890 and 0.929 in the training set, and 0.865 and 0.864 in the validation set, respectively.The multivariate Logistic regression model achieved ACC and AUC values of 0.870 and 0.854 in the training set, and 0.867 and 0.859 in the validation set, respectively. Conclusion:Anxiety, interpersonal sensitivity, learning pressure, mood swings, social anxiety, shame-proneness, and peer victimization are identified risk predictors of smartphone addiction in high school adolescents.

OBJECTIVE To investigate the effects of the split formulas of Biyuan Heji(BYHJ)on paranasal sinus mucosal in-flammation in rats with acute rhinosinusitis(ARS)based on the pathogenesis of"wind-cold transforming into lung-heat".METHODS Unilateral nasal cavity occlusion combined with nasal dripping of Staphylococcus aureus were performed to establish a rat model of ARS.SD rats were randomly divided into blank,model,BYHJ(wind-cold removal+lung-heat removal),lung-heat removal,wind-cold removal,and positive drug groups,with 6 rats in each group.The rats were treated with the corresponding drugs for 7 d and then the samples were collected.HE staining was used to observe the pathological changes of rat paranasal sinus mucosa tissues,ELISA was employed to determine the levels of interleukin-1β(IL-1β),IL-6,IL-8,IL-9,IL-10,and IL-12 in serum,immunohistochemis-try(IHC)was adopted to measure the protein expression of tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule(ICAM-1)in paranasal sinus mucosa tissues,and Western blot was used to detect the protein expression of phosphorylated p38 mito-gen-activated protein kinase(p38 MAPK),nuclear transcription factor-κB p50(NF-κB p50),and NF-κB p65 in paranasal sinus mucosa tissues.RESULTS The acute sinusitis rat inflammation model was successfully established.Compared with the model group,the water drinking,diet eating,and body weight of rats in the BYHJ group,wind-cold removal,lung-heat removal,and positive drug groups were significantly improved,the aggregation of inflammatory cells in the paranasal sinus mucosal tissue was reduced,and the levels of IL-1β,IL-6,IL-8,IL-9,and IL-12 in the serum were significantly reduced(P<0.01),IL-10 content significantly in-creased(P<0.01),the protein expression of TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 in the paranasal sinus mucosa was significantly decreased(P<0.01).The comparison between various traditional Chinese medicine groups showed that the decrease of IL-1β,IL-6,IL-8,IL-9,IL-12,TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 and the increase of IL-10 in the BYHJ group were better than those in the split formula groups(P<0.01),and the lung-heat removal group was better than the wind-cold removal group(P<0.01).CONCLUSION BYHJ and its split formulas can effectively inhibit the inflammatory response in rats with ARS.

OBJECTIVE To investigate the effect of dopamine receptor 3(D3R)on fear memory induced by intense electric shocks and the possible neurobiological mechanism.METHODS ① To prevent pain threshold differences from influencing the effect of intense electric shocks,wild-type(WT)and D3R knockout mice(D3R-/-)were used in the Hargreaves test to evaluate their basal pain threshold,with the paw withdrawal latency(PWL)as the observation index.② WT and D3R-/-mice were divided into control groups and model groups,respectively.On the training day(the first day,D 1),the model groups received inescapable electric shocks(1.5 mA,10 s,10 s interval,15 cycle)while the control groups did not.Contextual fear tests were conducted on D2,D7,D10,D14,and D16 after training,with the percentage of freezing time(FT)as the observation index to evaluate fear memory acquisition induced by contextual cues.On D17,after the model groups showed no more fear responses to contex-tual cues,they were re-stimulated with low-intensity current(0.5 mA,10 s,10 s interval,15 cycle)to evoke fear memory.The two control groups did not receive any shocks.Contextual fear tests were conducted on day 18,and the FT%of each group was observed to evaluate fear memory retrieval induced by contextual cues.③ Another cohort of WT and D3R-/-mice was used to further investigate the underlying neural mechanism,with the same grouping and treatment as in ②.Real-time dynamic changes in calcium signals of dopamine(DA)neurons in the ventral tegmental area(VTA)of WT and D3R-/-mice were detected using fiber photometry during electric shocks.The fluorescence area under the curve(AUC)was used as the indicator to quantify the excitability of DA neurons.RESULTS ① In the Hargreaves test,there was no significant difference in PWL between D3R-/-mice and WT mice,indi-cating the two genotype mice had no significant differences in the basal pain threshold.② Compared with the WT control group,the percentage of FT of the WT model group significantly increased on D2,D7,D10,and D14(P<0.05).Compared with the D3R-/-control group,the percentage of FT of the D3R-/-model group significantly increased only on D2 and D7(P<0.01).Meanwhile,the percentage of the FT of D3R-/-model group was significantly lower than in the WT control group on D2,D7,D10,and D14(P<0.05,P<0.01).During memory recall(D18),the percentage of FT of the WT model and D3R-/-model groups significantly increased compared to their respective control groups(P<0.01,P<0.05),while the percentage of FT of D3R-/-model mice was significantly lower than that of WT model mice(P<0.01).③ In the fiber photometry test,during the shock period,the calcium signals of DA neurons in the VTA of WT model and D3R-/-model mice rapidly increased within the first 2 s,and then gradually decreased between 2 to 10 s.The AUC within the 2 to 10 s interval was significantly lower in D3R-/-model mice compared to WT model mice(P<0.05),indicating that the excitability of DA neurons in the VTA of D3R-/-model mice was significantly lower than that of WT-model mice.CONCLUSION D3R knockout inhibits the acquisition and recall of long-term fear memory in mice,and its neurobiological mechanism may be related to the decreased excitability of DA neurons during electric shock.

Objective:To explore the impact of adolescent mental health status on smartphone addiction, and construct a predictive model for smartphone addiction based on the eXtreme Gradient Boosting(XGBoost) algorithm and multivariate Logistic regression.Methods:In April 2023, a cross-sectional survey was conducted among 14 666 adolescents.All participants were systematically evaluated using a self-developed general information questionnaire, the middle school student mental health scale(MSSMHS), the adolescents self-harm scale(ASHS), the interaction anxiousness scale(IAS), the mobile phone addiction index(MPAI), the middle school students shame scale(MSSS), the UCLA loneliness scale(UCLA-LS), the multidimensional peer victimization scale(MPVS), and the basic psychological needs scale(BPNS).R software version 4.3.2 was used for data analysis. Participants were randomly divided into training set and validation set at the ratio of 7∶3.The XGBoost model and multivariate logistic regression model were constructed to predict the risk of smartphone addiction, and a nomogram was plotted.Model performance was evaluated using the Hosmer-Lemeshow test, area under the curve(AUC), and accuracy(ACC).Results:(1) A total of 14 036 high school students were included in the study, with 5 069(36.1%) exhibited smartphone addiction.The training set comprised 9 826 students, with 3 549(36.1%) being smartphone addicts.The validation set included 4 210 students, with 1 520(36.1%) being smartphone addicts.(2) The XGBoost model identified shame-proneness and social anxiety as the two main predictors of smartphone addiction.(3) Multivariate Logistic regression analysis revealed that anxiety( B=0.328, OR(95% CI)=1.39(1.07-1.81), P=0.015), interpersonal sensitivity( B=0.311, OR(95% CI)=1.36(1.05-1.77), P=0.018), learning pressure( B=0.606, OR(95% CI)=1.83(1.46-2.31), P<0.001), mood swings( B=0.775, OR(95% CI)=2.17(1.70-2.78), P<0.001), social anxiety( B=0.024, OR(95% CI)=1.02(1.01-1.04), P<0.001), shame-proneness( B=0.049, OR(95% CI)=1.05(1.04-1.06), P<0.001), and peer victimization( B=0.037, OR(95% CI)=1.04(1.02-1.06), P<0.001) were significant predictors of smartphone addiction.(4) The ACC and AUC values of the XGBoost model were 0.890 and 0.929 in the training set, and 0.865 and 0.864 in the validation set, respectively.The multivariate Logistic regression model achieved ACC and AUC values of 0.870 and 0.854 in the training set, and 0.867 and 0.859 in the validation set, respectively. Conclusion:Anxiety, interpersonal sensitivity, learning pressure, mood swings, social anxiety, shame-proneness, and peer victimization are identified risk predictors of smartphone addiction in high school adolescents.

Objective:To establish the predictive model for major adverse cardiovascular events(MACE) following endovascular repair in elderly patients with abdominal aortic aneurysm(AAA).Methods:The clinical data and postoperative MACE were retrospectively collected from elderly patients with AAA who underwent their first endovascular aneurysm repair(EVAR)in Beijing Hospital and Tibet Autonomous Region People's Hospital between January 2016 and December 2023.Patients were randomly divided into training and validation cohorts at a ratio of 7∶3.Predictive models were using logistic regression, LASSO regression, random forest, linear discriminant analysis, na?ve Bayes, k-nearest neighbor algorithm, support vector machine, decision tree, and AdaBoost.Models were evaluated using receiver operating characteristic(ROC)curves.Results:A total of 171 elderly AAA patients were enrolled, aged 60 to 94 years(mean 73.0 ± 7.5 years), of whom 145 were male.MACE occurred after EVAR in 30 patients(17.5%). LASSO regression identified monocyte count, history of coronary artery disease, the ratio of maximum AAA diameter to body mass index(DBR), neutrophil-lymphocyte count ratio(NLR), and age as significant predictors, yielding an area under the ROC curve(AUC)of 0.816.Logistic regression achieved an AUC of 0.813 in the training cohort and 0.772 in the validation cohort.Among all models, AdaBoost demonstrated the best performance, with an AUC of 0.92 in the validation cohort.Conclusions:Age, monocyte count, DBR, NLR and creatinine could predict the occurrence of MACE after EVAR in AAA patients.The AdaBoost model provides the most accurate prediction of postoperative MACE.