PURPOSE: Early mortality in major trauma has decreased, but MODS remains a leading cause of poor outcomes, driven by trauma-induced cytokine storms that exacerbate injuries and organ damage. METHODS: This prospective cohort study included 79 major trauma patients (ISS >15) treated in the National Center for Trauma Medicine, Peking University People's Hospital, from September 1, 2021, to July 31, 2023. Patients (1) with ISS >15 (according to AIS 2015), (2) aged 15-80 years, (3) admitted within 6 h of injury, (4) having no prior treatment before admission, were included. Exclusion criteria were (1) GCS score <9 or AIS score ≥3 for TBI, (2) confirmed infection, infectious disease, or high infection risk, (3) pregnancy, (4) severe primary diseases affecting survival, (5) recent use of immunosuppressive or cytotoxic drugs within the past 6 months, (6) psychiatric patients, (7) participation in other clinical trials within the past 30 days, (8) patients with incomplete data or missing blood samples. Admission serum inflammatory cytokines and pathophysiological data were analyzed to develop machine learning models predicting MODS within 7 days. LR, DR, RF, SVM, NB, and XGBoost were evaluated based on the area under the AUROC. The SHAP method was used to interpret results. RESULTS: This study enrolled 79 patients with major trauma, and the median (Q₁, Q₃) age was 51 (35, 59) years (52 males, 65.8%). The inflammatory cytokine data were collected for all participants. Among these patients, 35 (44.3%) developed MODS, and 44 (55.7%) did not. Additionally, 2 patients (2.5%) from the MODS group succumbed. The logistic regression model showed strong performance in predicting MODS. Ten key cytokines, IL-18, Eotaxin, MCP-4, IP-10, CXCL12, MIP-3α, MCP-1, IL-1RA, Cystatin C, and MRP8/14 were identified as critical to the trauma-induced cytokine storm and MODS development. Early elevation of these cytokines achieved high predictive accuracy, with an AUROC of 0.887 (95% CI 0.813-0.976). CONCLUSION Trauma-induced cytokine storms are strongly associated with MODS. Early identification of inflammatory cytokine changes enables better prediction and timely interventions to improve outcomes.
Humans ; Prospective Studies ; Middle Aged ; Male ; Female ; Adult ; Aged ; Cytokine Release Syndrome/etiology* ; Adolescent ; Young Adult ; Aged, 80 and over ; Wounds and Injuries/complications* ; Cytokines/blood* ; Multiple Organ Failure/diagnosis* ; Machine Learning

A middle-aged patient presented with persistent purulent discharge from a scalp incision five years after undergoing craniotomy with artificial dura mater implantation. The wound showed no significant improvement despite a month of systemic antibiotic therapy and local debridement. Subsequent superficial ultrasonography revealed complete separation of the artificial dura mater implant area from the surrounding flap tissue, with a loss of local blood supply. Based on these findings, the artificial dura mater was surgically removed, and a free skin flap transplantation was performed to successfully cover the wound. The wound was well-healed at the 10-month postoperative follow-up.
Humans ; Scalp/diagnostic imaging* ; Middle Aged ; Male ; Epidural Abscess/etiology* ; Ultrasonography ; Surgical Flaps ; Surgical Wound Infection/surgery* ; Dura Mater/surgery*

OBJECTIVES: To explore whether the antioxidant axis Nrf2/HO-1 is involved in the regulation of hippocampus injury induced by cypermethrin and its underlying mechanism. METHODS: Ten-week-old C57BL/6 mice were randomly divided into control group and cypermethrin exposure groups with low, medium, and high exposure levels. After 21 days of oral gavage of corn oil (control) or cypermethrin, the levels of MDA, T-SOD, GSH-Px and CAT in the hippocampus of the mice were examined to evaluate the oxidative stress levels. HE staining was used to observe morphological changes of the hippocampal neurons. Western blotting, immunofluorescence staining and RT-qPCR were employed to detect the protein expressions and mRNA expression of Nrf2 and HO-1 and HO-1. RESULTS: Subacute oral exposure to cypermethrin significantly increased MDA level, decreased the activities of antioxidant enzymes T-SOD, GSH-Px and CAT, and induced neuronal damage in the CA1 and CA3 regions in the hippocampus of C57BL/6 mice. Cypermethrin exposure also caused Nrf2 protein translocation from the cytoplasm to the nucleus, accompanied by upregulated expression levels of the key antioxidant factor Nrf2 and its downstream target kinase HO-1. CONCLUSIONS Cypermethrin exposure dose-dependently causes oxidative damage in the hippocampus of C57BL/6 mice, which is regulated by the Nrf2/HO-1 antioxidant pathway.
Animals ; Pyrethrins/toxicity* ; NF-E2-Related Factor 2/metabolism* ; Hippocampus/cytology* ; Mice, Inbred C57BL ; Mice ; Oxidative Stress/drug effects* ; Neurons/pathology* ; Heme Oxygenase-1/metabolism* ; Signal Transduction ; Membrane Proteins

OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels. METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient. The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology. The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software （V11.1.2.4）. RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL； a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL. The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL， while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL. Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation， the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate （eGFR） 0-30 mL/min was 5 mg once daily； for patients with eGFR＞30-60 mL/min， the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily； for patients with eGFR＞60-90 mL/min， the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily； for patients with eGFR＞90-120 mL/min， the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily. For patients with venous thrombosis， it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min； the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min， 25- 30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min， 10-15 mg twice daily for patients with eGFR＞ 90-120 mL/min. CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment. Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability. The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method， taking into account patients’ renal function.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Objective To explore the effects of image registration using various regions of interest(ROI)on the setup error for nasopharyngeal carcinoma(NPC)patients who were immobilized individually.Methods Forty-three NPC patients who required radiotherapy were enrolled.The patients were immobilized with customized plastic foam and thermoplastic mask,and CBCT verification was performed once a week.In CBCT images,ROI was divided into the whole ROI(ROIPTV)and 7 local ROI containing different cervical structures(ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,ROIneck4,ROIneck5,ROIneck6,and ROIneck7),which were then used for registrations with localized CT image.The setup errors in superior-inferior(SI),left-right(LR),anterior-posterior(AP),Pitch,Roll,and Yaw directions were recorded.Results In SI direction,the setup errors within 0.3 cm accounted for 89.74%for ROIneck7,and more than 90%for the other ROI.The proportion of setup errors within 0.3 cm gradually increased with the neck upward in LR direction,and they were 76.78%,81.70%,85.26%,and above 90%for ROIneck7,ROIneck6,ROIneck5,and the other ROI,respectively.In AP direction,the proportions of setup errors within 0.3 cm were less than 90%,except for ROIatlantoaxial and ROIneck3.The setup errors of ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,and ROIneck4 were significantly positively correlated with ROIPTV in SI direction,and the correlation coefficients(R)were 0.94,0.95,0.90,and 0.83,respectively.In LR direction,there were positive correlations between the setup errors of ROIatlantoaxial and ROIsphenoid sinus(R=0.95),ROIneck3 and ROIsphenoid sinus(R=0.91),ROIPTV and ROIneck3(R=0.91).The setup errors of ROIPTV in AP direction were positively correlated with ROIatlantoaxial vertebrae and ROIneck3(R=0.88,0.90).The margins of all ROIs ranged from 0.38 cm to 1.01 cm.The extension of ROIneck6 and ROIneck7 in AP direction exceeded 0.9 cm,and the extension of ROIneck7 reached 0.95 cm in SI direction.Conclusion ROIPTV and ROIsphenoid sinus,ROIatlantoaxial,ROIneck3 are significantly correlated in SI,LR,and AP directions.The setup error of nasopharyngeal carcinoma patients gradually increases with the neck down.The nasopharyngeal and cervical regions need to be expanded in segments when patients are immobilized individually.

As the continuation of the left ventricle,the left atrium and left ventricle interact and play an important role in the function of the whole heart.At present,there are many techniques to evaluate the atrial structure and function,but the left atrial structure is complex and the myocardium is thin,which brings some challenges to the relevant evaluation.This paper introduces the parameters,precautions and relevant clinical applications in the process of left atrial evaluation from the aspects of myocardial strain and delayed enhancement.

Objective To investigate the effect of resveratrol(RES)on ovarian function in mice and elucidate the potential mechanism involving miR-23a.Methods Thirty mice were randomly divided into control,premature ovarian failure(POF)model,and treatment(RES)groups,with n=10 per group.The body weight and ovarian mass of the mice were measured,and the ovarian index was calculated.Hematoxylin and eosin staining was performed to observe pathological changes in mouse ovarian tissue.Real-time quantitative PCR and Western blotting were performed to measure the mRNA and protein levels of miR-23a,X-linked inhibitor of apoptosis protein(XIAP),and caspase-3 in the ovarian tissue.Results Compared with the control group,the POF group exhibited significant decreases in ovarian mass(P＜0.05),ovarian index(P＜0.05),number of primary follicles,and XIAP mRNA expression(P＜0.05),alongside significant increases in miR-23a and caspase-3 mRNA expression(P＜0.05).Compared with the POF group,the RES group exhibited significant increases in the ovarian mass(P＜0.05),ovarian index(P＜0.05),number of primary follicles,and XIAP mRNA expression(P＜0.05),as well as significant decreases in miR-23a and caspase-3 mRNA expression(P＜0.05).XIAP protein expression was significantly lower and caspase-3 protein expression was significantly higher in the POF group than in the control group(P＜0.05).Conversely,XIAP protein expression was significantly higher and caspase-3 protein expression was significantly lower in the RES group than in the POF group(P＜0.05).Conclusion RES exerts a protective effect on weakened ovarian function in mice,potentially mediated through its effect on miR-23a targeting the XIAP-caspase-3 signaling pathway.

The gene encoding regulatory subunit 15 A of protein phosphatase 1 produces a protein that is a universally present protein phosphatase in eukaryotic cells.In this study,genomic DNAs were extracted from the blood of 89 Chinese Holstein cows and were used as templates for PCR amplification of the target fragment of the PPP1R15A gene.The product was tested and a polymor-phic site,E3-250T＞A was found.The polymorphism of this side and its correlation with milk pro-duction traits in Chinese Holstein cattle were statistically analyzed using SPSS 23.0 software.The findings revealed three genotypes at this site:AA,AT and TT.Cows possessing the AT and TT genotypes exhibited significant differences(P＜0.01)in milk fat and solid non-fat content com-pared to those with the AA genotype.While no significant differences were noted for other milk production traits,including milk yield,protein,lactose,somatic cell count,blood urea nitrogen,and corrected milk.The identification of functional SNPs in the PPP1R15A gene provides a theoretical basis for further research and identification of causal variations in the cow PPP1R15A gene.

Objective To explore the role and mechanism of glycogen synthase kinase 3β(GSK3 β)/fission protein 1(Fis1)signa-ling pathway in the apoptosis of osteoblast induced by methylglyoxal.Methods LiCl was used as GSK3β inhibitor,and the cells were randomly divided into 4groups:control group,MG group,LiCl group,LiCl+MG group.The cell proliferation activity was detected by MTT assays.The cell apoptosis was analyzed by Tunel assays.The protein expression levels of GSK3β and Fis1 were detected by Western blot.Mitochondrial morphology was analyzed by MitoTracker Deep Red.Results MTT assay showed that MG inhibited the proliferation activity of osteoblast.Tunel staining showed that MG induced osteoblast apoptosis.Western blot assay showed that the phosphorylation lev-el of GSK3β decreased and the expression level of Fis1 protein increased after MG treatment.MitoTracker Deep Red staining showed that mitochondrion were fragmented after MG treatment.After the addition of GSK3β inhibitor LiCl,compared with the MG group,the MG-inhibited cell proliferation activity and apoptosis were significantly restored.Meanwhile,the phosphorylation level of GSK3β protein was increased,the expression level of Fis1 protein was decreased,and the mitochondrial morphology was restored.Conclusion MG may pro-mote the increase of mitochondrial division and induce osteoblast apoptosis by regulating GSK3 β/Fis1 signaling pathway.