Objective: To develop and validate a clinically actionable prediction model for postoperative pulmonary complications (PPCs) in cardiac surgery patients, focusing on modifiable preoperative risk factors amenable to targeted optimization. Methods: In this prospective observational cohort study, 492 adults undergoing open-chest cardiac surgery between August 15, 2023 and December 31, 2023 were analyzed. Prespecified predictors included gas exchange variables, pulmonary function, inspiratory muscle strength, and physical performance. Univariable and multivariable logistic regression analyses were used to develop the prediction model. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Results: A total of 90 patients (14.1%) developed PPCs after surgery. Five independent predictors were identified: elevated arterial PaCO2 (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.26), oxygen desaturation (SpO2<93%) (OR 12.47, 95% CI 3.51–48.13), reduced gait speed (OR 0.17, 95% CI 0.04–0.71), lower FEV1/FVC ratio (OR 0.96, 95% CI 0.92–1.00), and diminished inspiratory muscle strength (MIP % predicted) (OR 0.96, 95% CI 0.92–0.99). The model demonstrated good discriminative ability with an AUC of 0.86 (95% CI 0.80–0.93) in the training cohort and 0.87 (95% CI 0.74–0.93) in the validation cohort. Conclusion This parsimonious model achieved high predictive accuracy using five modifiable physiological variables. By targeting abnormalities in gas exchange, pulmonary mechanics, muscle strength, and functional reserve, the model offers a practical tool to guide individualized prehabilitation strategies for reducing PPC risk in cardiac surgery patients.

Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objectives:To explore the correlation between preoperative frailty and postoperative pulmonary complications in elderly patients undergoing cardiac surgery,and to provide a scientific basis for the comprehensive perioperative management of these patients.Methods:In this prospective cohort study,elderly patients(≥60 years old)who were scheduled to undergo coronary artery bypass grafting(CABG)and/or heart valve surgery at Fuwai Hospital,Chinese Academy of Medical Sciences from December 2022 to December 2023 were consecutively enrolled.Patients were divided into the postoperative pulmonary complication group and the non-postoperative pulmonary complication group based on whether they developed postoperative pulmonary complications.Demographic data,preoperative frailty status,physical function indicators(6-meter walking speed,pulmonary function),laboratory test indicators,and surgical data of the two groups were collected and compared.Multivariate logistic regression analysis was used to evaluate the correlation between preoperative frailty and postoperative pulmonary complications in these patients.Results:A total of 522 patients were included in the study,66(12.6%)had preoperative frailty.There were 159 cases(30.5%)in the postoperative pulmonary complication group and 363 cases(69.5%)in the non-postoperative pulmonary complication group.Compared with the non-postoperative pulmonary complication group,the postoperative pulmonary complication group had a higher prevalence of preoperative frailty,cerebral infarction,and pulmonary hypertension,lower maximal inspiratory pressure,slower 6-meter walking speed,a higher proportion of patients undergoing heart valve surgery and CABG+heart valve surgery,and significantly longer mechanical ventilation time,intensive care unit stay,and postoperative hospital stay(all P<0.05).Multivariate logistic regression analysis showed that preoperative frailty(OR=1.998,95%CI:1.005-3.973,P=0.048),maximal inspiratory pressure(OR=0.987,95%CI:0.977-0.997,P=0.011),6-meter walking speed(OR=0.003,95%CI:0.001-0.017,P<0.001),mechanical ventilation time(OR=2.295,95%CI:1.601-3.290,P<0.001),and CABG+heart valve surgery(OR=1.772,95%CI:1.294-2.428,P<0.001)were independent risk factors of postoperative pulmonary complications in elderly patients undergoing cardiac surgery.Conclusions:Preoperative frailty increases the risk of postoperative pulmonary complications in elderly patients undergoing cardiac surgery.

Objectives:To analyze and compare the clinical efficacy of traditional titanium mesh and three-dimensional(3D)printed artificial vertebral bodies in anterior cervical corpectomy and fusion(ACCF).Methods:A retrospective analysis was conducted on 42 patients with cervical spondylotic myelopathy who underwent single segment ACCF at our hospital from January 2015 to January 2024.The patients were divid-ed into a traditional titanium mesh group(n=22,9 males and 13 females,aged 60.6±10.0 years)and a 3D printed artificial vertebral body group(n=20,10 males and 10 females,aged 55.5±8.3 years)based on the type of implant.There was no statistical difference between the two groups in age,gender,body mass index(BMI),as well as affected segments(P＞0.05).The operative time,intraoperative blood loss,and length of hos-pital stay,as well as imaging parameters(C2-7 Cobb angle),neurological function[Japanese Orthopaedic Associ-ation(JOA)score and Nurick grading],neck pain visual analogue scale(VAS)score,and neck disability index(NDI)before operation,at postoperative 3d and 1 year were recoreded and compared between the two groups,meanwhile,the postoperative cage deposition and other complications were also analyzed and compared.Re-sults:There was no significant difference in the operative time between the two groups of cases(P＞0.05).The intraoperative blood loss and postoperative length of hospital stay of the 3D printed artificial vertebral body group were significantly lower than those in the traditional titanium mesh group(P＜0.05).At each postoperative time point,both groups showed significant improvement in JOA scores,Nurick grading,VAS scores,and NDI scores compared to preoperative levels.However,there were no significant differences in JOA scores,Nurick grading,VAS scores,and NDI scores between the two groups of patients at preoperation,postoperative 3d,and postoperative 1 year.According to radiological measurement analysis,both groups of patients showed great improvement in the C2-7 Cobb angle after surgery,and 3D printed artificial vertebral body group was better than traditional titanium mesh group in C2-7 Cobb angle on postoperative 3d(20.2°±10.1° vs 13.8°±9.8°,P＜0.05)and at 1 year follow-up(19.7°±10.2° vs 13.0°±9.7°,P＜0.05).There was one case of cage settlement in the traditional titanium mesh group,while no cage settlement was found in the 3D printed artificial vertebral body group during follow-up.Conclusions:Both traditional titanium mesh and 3D printed artificial vertebral body in ACCF can effectively treat cervical spondylotic myelopathy and significantly improve patients' symptoms.However,the application of 3D printed artificial vertebral bodies can significantly reduce intraoperative bleeding and postoperative hospitalization days for patients.Moreover,3D printed artificial vertebral bodies have more advantages in maintaining the physiological structure of the cervical spine.

Objectives:To analyze and compare the clinical efficacy of traditional titanium mesh and three-dimensional(3D)printed artificial vertebral bodies in anterior cervical corpectomy and fusion(ACCF).Methods:A retrospective analysis was conducted on 42 patients with cervical spondylotic myelopathy who underwent single segment ACCF at our hospital from January 2015 to January 2024.The patients were divid-ed into a traditional titanium mesh group(n=22,9 males and 13 females,aged 60.6±10.0 years)and a 3D printed artificial vertebral body group(n=20,10 males and 10 females,aged 55.5±8.3 years)based on the type of implant.There was no statistical difference between the two groups in age,gender,body mass index(BMI),as well as affected segments(P＞0.05).The operative time,intraoperative blood loss,and length of hos-pital stay,as well as imaging parameters(C2-7 Cobb angle),neurological function[Japanese Orthopaedic Associ-ation(JOA)score and Nurick grading],neck pain visual analogue scale(VAS)score,and neck disability index(NDI)before operation,at postoperative 3d and 1 year were recoreded and compared between the two groups,meanwhile,the postoperative cage deposition and other complications were also analyzed and compared.Re-sults:There was no significant difference in the operative time between the two groups of cases(P＞0.05).The intraoperative blood loss and postoperative length of hospital stay of the 3D printed artificial vertebral body group were significantly lower than those in the traditional titanium mesh group(P＜0.05).At each postoperative time point,both groups showed significant improvement in JOA scores,Nurick grading,VAS scores,and NDI scores compared to preoperative levels.However,there were no significant differences in JOA scores,Nurick grading,VAS scores,and NDI scores between the two groups of patients at preoperation,postoperative 3d,and postoperative 1 year.According to radiological measurement analysis,both groups of patients showed great improvement in the C2-7 Cobb angle after surgery,and 3D printed artificial vertebral body group was better than traditional titanium mesh group in C2-7 Cobb angle on postoperative 3d(20.2°±10.1° vs 13.8°±9.8°,P＜0.05)and at 1 year follow-up(19.7°±10.2° vs 13.0°±9.7°,P＜0.05).There was one case of cage settlement in the traditional titanium mesh group,while no cage settlement was found in the 3D printed artificial vertebral body group during follow-up.Conclusions:Both traditional titanium mesh and 3D printed artificial vertebral body in ACCF can effectively treat cervical spondylotic myelopathy and significantly improve patients' symptoms.However,the application of 3D printed artificial vertebral bodies can significantly reduce intraoperative bleeding and postoperative hospitalization days for patients.Moreover,3D printed artificial vertebral bodies have more advantages in maintaining the physiological structure of the cervical spine.

Objectives:To explore the correlation between preoperative frailty and postoperative pulmonary complications in elderly patients undergoing cardiac surgery,and to provide a scientific basis for the comprehensive perioperative management of these patients.Methods:In this prospective cohort study,elderly patients(≥60 years old)who were scheduled to undergo coronary artery bypass grafting(CABG)and/or heart valve surgery at Fuwai Hospital,Chinese Academy of Medical Sciences from December 2022 to December 2023 were consecutively enrolled.Patients were divided into the postoperative pulmonary complication group and the non-postoperative pulmonary complication group based on whether they developed postoperative pulmonary complications.Demographic data,preoperative frailty status,physical function indicators(6-meter walking speed,pulmonary function),laboratory test indicators,and surgical data of the two groups were collected and compared.Multivariate logistic regression analysis was used to evaluate the correlation between preoperative frailty and postoperative pulmonary complications in these patients.Results:A total of 522 patients were included in the study,66(12.6%)had preoperative frailty.There were 159 cases(30.5%)in the postoperative pulmonary complication group and 363 cases(69.5%)in the non-postoperative pulmonary complication group.Compared with the non-postoperative pulmonary complication group,the postoperative pulmonary complication group had a higher prevalence of preoperative frailty,cerebral infarction,and pulmonary hypertension,lower maximal inspiratory pressure,slower 6-meter walking speed,a higher proportion of patients undergoing heart valve surgery and CABG+heart valve surgery,and significantly longer mechanical ventilation time,intensive care unit stay,and postoperative hospital stay(all P<0.05).Multivariate logistic regression analysis showed that preoperative frailty(OR=1.998,95%CI:1.005-3.973,P=0.048),maximal inspiratory pressure(OR=0.987,95%CI:0.977-0.997,P=0.011),6-meter walking speed(OR=0.003,95%CI:0.001-0.017,P<0.001),mechanical ventilation time(OR=2.295,95%CI:1.601-3.290,P<0.001),and CABG+heart valve surgery(OR=1.772,95%CI:1.294-2.428,P<0.001)were independent risk factors of postoperative pulmonary complications in elderly patients undergoing cardiac surgery.Conclusions:Preoperative frailty increases the risk of postoperative pulmonary complications in elderly patients undergoing cardiac surgery.

Objective: To analyze the correlation and gender differences between adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) and depression and anxiety symptoms among middle school students, so as to provide a reference for promoting the mental health of middle school students. Methods: With a stratified random cluster sampling method, a total of 6 656 middle school students in 4 cities, including Nanchang, Shenyang, Taiyuan, and Zhengzhou, were selected as research subjects from October 2021 to October 2022. The Adverse Childhood Experiences International Questionnaire (ACEs-IQ), Benevolent Childhood Experiences Scale (BCEs), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorders-7 (GAD-7) scale were used to conduct questionnaire surveys.The Chi square test was used to compare the reporting rates of depression and anxiety symptoms among middle school students in different groups, and a Logistic regression model was established to analyze the effects of ACEs and PCEs on depression and anxiety symptoms among middle school students and their gender differences. Results: The reporting rate of depressive symptoms among middle school students was 20.1%, and the reporting rate of anxiety symptoms was 13.9% . ACEs were positively correlated with depression and anxiety symptoms among middle school students (depression symptoms: OR =1.20, 95% CI =1.18-1.22, anxiety symptoms: OR =1.18, 95% CI =1.16-1.20), while PCEs were negatively correlated with depression and anxiety symptoms among middle school students(depression symptoms: OR =0.84, 95% CI = 0.83 -0.86, anxiety symptoms: OR =0.85, 95% CI =0.83-0.87) ( P <0.05). In the general population (depression symptoms ： OR =0.99, 95% CI = 0.98- 0.99, anxiety symptoms: OR =0.99, 95% CI =0.99-1.00) and among girls (depression symptoms: OR = 0.98 , 95% CI = 0.97- 0.99 , anxiety symptoms ： OR =0.99, 95% CI =0.98-1.00), the interaction term between ACEs and PCEs were negatively correlated with depression and anxiety symptoms ( P <0.05). Conclusions ACEs significantly affect the depression and anxiety symptoms of middle school students, while PCEs can help reduce the impact of ACEs on the depression and anxiety symptoms of middle school students, girls are more susceptible to the impact of early experiences than boys. It should focus on gender differences, formulate comprehensive mental health protection strategies, to promote the mental health development of middle school students.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.
Humans ; Male ; Child ; Female ; Acoustic Stimulation ; Autistic Disorder/physiopathology* ; Arousal/physiology* ; Pupil/physiology* ; Habituation, Psychophysiologic/physiology* ; Auditory Perception ; Child, Preschool