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.

3D printing technology customized medical devices can accurately adapt to the complex anatomical structure of the human body, and have become a new meaning to promote the development of precision medicine. In order to ensure the safety and effectiveness of the clinical use of 3D printed customized medical devices and standardize the management process of such products, a tertiary hospital had started the file-record management of 3D printed customized medical devices since March 2021, covering access approval management, production verification, surgical process management and postoperative traceability management. This practice had achieved standardized management of 3D printed customized medical devices and achieved good results. The 3D printed bone fixation fusion used by the hospital was officially approved as a medical device product registration certificate in March 2023; 109 orthopedic patients recorded the use of 3D printed custom medical devices in 2023, with a significant increase compared to 54 patients in 2022. This practice could provide references for other hospitals to carry out standardized management of the use of customized medical devices. In the future, hospital should further balance regulation and innovation, promote multi-party collaboration, strengthen data integration, ensure data security, and enhance the level of refined management of medical devices.

Objective:To explore the clinical value of multi-parameter combined monitoring in guiding low-molecular-weight heparin (LMWH) therapy for intensive care unit (ICU) patients.Methods:A retrospective case-control study was conducted. A total of 381 patients who received LMWH therapy with anti-Ⅹa activity monitoring in the ICU of West China Hospital, Sichuan University between January 31st, 2022, and November 30th, 2023, were enrolled in this study. The cohort comprised 264 males and 117 females, with the age of 58 (48, 71) years old. Clinical data and relevant laboratory parameters were collected, including anti-Ⅹa activity, antithrombin activity (AT), thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PIC), conventional coagulation parameters such as activated partial thromboplastin time (APTT), and indicators of hepatic/renal impairment such as alanine aminotransferase (ALT) and creatinine( CREA). Patients were stratified into three groups based on thrombotic event: thrombosis-controlled, progressive thrombosis, and bleeding group. Single-factor and adjusted multifactorial Logistic regression analysis were used to identify independent predictors of anti-xa activity levels.Results:Among 381 patients, thrombosis was controlled in 213 (55.9%) patients, progressed in 81 (21.3%) patients , and bleeding events occurred in 87 (22.8%) patients. The patients whose anti-Ⅹa activity levels lay entirely within the target range(0.2-0.4 IU/ml): Only 35 (16.4%) cases in the thrombosis-controlled group, 16 (19.7%) cases in the progressive thrombosis group, and 16 (18.4%) in the bleeding group. No significant differences in anti-Ⅹ a levels activity among the three groups ( H=1.678, P=0.432). Both single-factor and adjusted multifactorial Logistic regression identified low AT activity as an independent risk factor for failure to achieve target anti-Ⅹ a activity levels (AT nadir, OR=1.031,95% CI 1.016-1.046, P<0.05). Compared with the progressive thrombosis and bleedinggroup, the thrombosis-controlled group exhibited significantly higher proportion of TAT values below the cut-off value ( H=8.519, P=0.014), and a higher proportion of TAT/PIC ratios below the cut-off ( H=15.56, P<0.001). Patients with bleeding demonstrated significantly lower AT activity ( H=14.968, P=0.001), prolonged APTT ( H=6.815, P=0.033), higher ALT ( H=13.774, P=0.001), and higher CREA ( H=14.068, P=0.001) compared with the thrombosis-controlled or progressive thrombosis group. Conclusion:Laboratory monitoring is required for low-molecular-weight heparin (LMWH) therapy in ICU patients. While anti-Ⅹa activity reflects the anticoagulant effect of LMWH, the utility of anti-Ⅹ a activity for predicting thrombotic or hemorrhagic risks in LMWH treated ICU patients is limited. Reductions in TAT levels and TAT/PIC ratios are associated with a lower risk of thrombotic progression. Furthermore, abnormalities in conventional coagulation tests and standard hepatic/renal function parameters occur more frequently in patients experiencing hemorrhagic events.

Objective:To analyze the application of antitoxin therapy in severe infant botulism.Methods:A retrospective analysis was conducted on 14 cases of severe infant botulism treated at 3 pediatric medical centers from July 2020 to August 2024. This study investigated antitoxin dosage, treatment duration, discontinuation criteria and adverse reactions.Results:A total of 14 cases (12 males and 2 females) were included, with an age of 5.0 (3.8, 7.0) months. Botulinum toxin typing revealed 10 cases of Type B, 2 cases of Type A and 2 untyped cases. The interval from symptom onset to antitoxin administration was 9.0 (6.0, 11.5) d. The initial dosage of type A antitoxin was 12 500 (10 000, 22 500) U, while type B was 5 000 (5 000, 5 000) U. The dosage was tapered in some cases after symptom improvement, the duration of treatment was 16.5 (9.8, 25.3) d. In total, 11 infants discontinued medications after improvement in muscle strength, while 3 infants discontinued treatment after obtaining negative results from fecal mouse bioassays. Adverse events were reported in 2 cases, both of which resulted in rash, and 1 case was complicated with anaphylactic shock. All the patients survived upon discharge with a follow-up period of 11 d to 3 years and 8 months. Totally 12 infants had fully recovered, while 2 infants were still recovering after discharge.Conclusion:Antitoxin therapy is a feasible and safe approach which showed favorable prognosis in severe infant botulism.

Recent rapid developments in molecular biological techniques have allowed the use of gene editing,as a means of genome modification,for the establishment of experimental animal models,with high efficiency,accuracy,and flexibility.This article mainly summarizes the construction and application of the latest gene-editing techniques in animal models,including pigs,non-human primates and dogs.It provides a theoretical reference for the application and in-depth study of gene-editing techniques in large experimental animals,which may better simulate human diseases,and for further studies of the potential pathogenesis of biomedical and human complex diseases.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Recent rapid developments in molecular biological techniques have allowed the use of gene editing,as a means of genome modification,for the establishment of experimental animal models,with high efficiency,accuracy,and flexibility.This article mainly summarizes the construction and application of the latest gene-editing techniques in animal models,including pigs,non-human primates and dogs.It provides a theoretical reference for the application and in-depth study of gene-editing techniques in large experimental animals,which may better simulate human diseases,and for further studies of the potential pathogenesis of biomedical and human complex diseases.

Objective:To analyze the application of antitoxin therapy in severe infant botulism.Methods:A retrospective analysis was conducted on 14 cases of severe infant botulism treated at 3 pediatric medical centers from July 2020 to August 2024. This study investigated antitoxin dosage, treatment duration, discontinuation criteria and adverse reactions.Results:A total of 14 cases (12 males and 2 females) were included, with an age of 5.0 (3.8, 7.0) months. Botulinum toxin typing revealed 10 cases of Type B, 2 cases of Type A and 2 untyped cases. The interval from symptom onset to antitoxin administration was 9.0 (6.0, 11.5) d. The initial dosage of type A antitoxin was 12 500 (10 000, 22 500) U, while type B was 5 000 (5 000, 5 000) U. The dosage was tapered in some cases after symptom improvement, the duration of treatment was 16.5 (9.8, 25.3) d. In total, 11 infants discontinued medications after improvement in muscle strength, while 3 infants discontinued treatment after obtaining negative results from fecal mouse bioassays. Adverse events were reported in 2 cases, both of which resulted in rash, and 1 case was complicated with anaphylactic shock. All the patients survived upon discharge with a follow-up period of 11 d to 3 years and 8 months. Totally 12 infants had fully recovered, while 2 infants were still recovering after discharge.Conclusion:Antitoxin therapy is a feasible and safe approach which showed favorable prognosis in severe infant botulism.

3D printing technology customized medical devices can accurately adapt to the complex anatomical structure of the human body, and have become a new meaning to promote the development of precision medicine. In order to ensure the safety and effectiveness of the clinical use of 3D printed customized medical devices and standardize the management process of such products, a tertiary hospital had started the file-record management of 3D printed customized medical devices since March 2021, covering access approval management, production verification, surgical process management and postoperative traceability management. This practice had achieved standardized management of 3D printed customized medical devices and achieved good results. The 3D printed bone fixation fusion used by the hospital was officially approved as a medical device product registration certificate in March 2023; 109 orthopedic patients recorded the use of 3D printed custom medical devices in 2023, with a significant increase compared to 54 patients in 2022. This practice could provide references for other hospitals to carry out standardized management of the use of customized medical devices. In the future, hospital should further balance regulation and innovation, promote multi-party collaboration, strengthen data integration, ensure data security, and enhance the level of refined management of medical devices.

Objective:To explore the clinical value of multi-parameter combined monitoring in guiding low-molecular-weight heparin (LMWH) therapy for intensive care unit (ICU) patients.Methods:A retrospective case-control study was conducted. A total of 381 patients who received LMWH therapy with anti-Ⅹa activity monitoring in the ICU of West China Hospital, Sichuan University between January 31st, 2022, and November 30th, 2023, were enrolled in this study. The cohort comprised 264 males and 117 females, with the age of 58 (48, 71) years old. Clinical data and relevant laboratory parameters were collected, including anti-Ⅹa activity, antithrombin activity (AT), thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PIC), conventional coagulation parameters such as activated partial thromboplastin time (APTT), and indicators of hepatic/renal impairment such as alanine aminotransferase (ALT) and creatinine( CREA). Patients were stratified into three groups based on thrombotic event: thrombosis-controlled, progressive thrombosis, and bleeding group. Single-factor and adjusted multifactorial Logistic regression analysis were used to identify independent predictors of anti-xa activity levels.Results:Among 381 patients, thrombosis was controlled in 213 (55.9%) patients, progressed in 81 (21.3%) patients , and bleeding events occurred in 87 (22.8%) patients. The patients whose anti-Ⅹa activity levels lay entirely within the target range(0.2-0.4 IU/ml): Only 35 (16.4%) cases in the thrombosis-controlled group, 16 (19.7%) cases in the progressive thrombosis group, and 16 (18.4%) in the bleeding group. No significant differences in anti-Ⅹ a levels activity among the three groups ( H=1.678, P=0.432). Both single-factor and adjusted multifactorial Logistic regression identified low AT activity as an independent risk factor for failure to achieve target anti-Ⅹ a activity levels (AT nadir, OR=1.031,95% CI 1.016-1.046, P<0.05). Compared with the progressive thrombosis and bleedinggroup, the thrombosis-controlled group exhibited significantly higher proportion of TAT values below the cut-off value ( H=8.519, P=0.014), and a higher proportion of TAT/PIC ratios below the cut-off ( H=15.56, P<0.001). Patients with bleeding demonstrated significantly lower AT activity ( H=14.968, P=0.001), prolonged APTT ( H=6.815, P=0.033), higher ALT ( H=13.774, P=0.001), and higher CREA ( H=14.068, P=0.001) compared with the thrombosis-controlled or progressive thrombosis group. Conclusion:Laboratory monitoring is required for low-molecular-weight heparin (LMWH) therapy in ICU patients. While anti-Ⅹa activity reflects the anticoagulant effect of LMWH, the utility of anti-Ⅹ a activity for predicting thrombotic or hemorrhagic risks in LMWH treated ICU patients is limited. Reductions in TAT levels and TAT/PIC ratios are associated with a lower risk of thrombotic progression. Furthermore, abnormalities in conventional coagulation tests and standard hepatic/renal function parameters occur more frequently in patients experiencing hemorrhagic events.