Objective:To preliminarily explore whether sirtuin1 (SIRT1) activation can inhibit neuronal ferroptosis in rats after traumatic brain injury (TBI) by regulating hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis.Methods:(1) Six SD rats were randomly divided into sham-operated group and TBI group, with 3 rats in each group; TBI model in the TBI group was established by hydraulic impact method, and rats in the sham-operated group underwent same surgery without impact. Cortical tissues of the two groups were sent for tandem mass tag (TMT) labeled quantitative proteomics detection to analyze the differential expression proteome; Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to detect pathway enrichment of the screened differential proteins. (2) Twelve SD rats were randomly divided into sham-operated group and 1-day, 3-day and 7-day post-TBI groups, with 3 rats in each group. Treatment methods were the same as above; Western blotting was used to detect SIRT1 protein expression. (3) Forty-eight rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+SIRT1 agonist group, with 12 rats in each group; rats in the sham-operated group and TBI group accepted treatment as above; rats in the TBI+SIRT1 agonist group were intraperitoneally injected with SRT1720 (dissolved in ≤ 5% dimethyl sulfoxide, at a dose of 20 mg/kg) within 30 minutes after modeling, twice a day (with an interval of 12 hours); and rats in the TBI+vehicle group were injected with same dose of dimethyl sulfoxide at the same time. One d after modeling, neurological deficit was assessed using modified Neurological severity score (mNSS), brain water content was measured by dry-wet weight method, histopathological changes in the cortical lesions were observed by HE staining, mitochondrial ultrastructure was examined by transmission electron microscopy, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the brain tissues were detected by colorimetry, and protein expressions of SIRT1, HIF-1α (key protein in the glycolytic pathway), glutathione peroxidase 4 (GPX4, key protein in the ferroptosis pathway), and acyl-CoA synthetase long-chain family member 4 (ACSL4, key protein in the ferroptosis pathway) were evaluated by Western blotting.Results:(1) KEGG analysis revealed that the glycolysis pathway and HIF-1 signaling pathway were obviously enriched in the cortical tissues of rats in the TBI group compared with the sham-operated group; GSEA showed that the HIF-1 signaling pathway (mmu04066) and ferroptosis pathway (mmu04216) gene sets in the cortical tissues of rats in the TBI group exhibited enrichment trends compared with those in the sham-operated group. (2) Compared with the sham-operated group, the 1-day, 3-day, and 7-day post-TBI groups had significantly decreased SIRT1 protein expression ( P<0.05), with the most prominent decline in 1-day post-TBI group. (3) Compared with the TBI+vehicle group, rats in the TBI+SIRT1 agonist group showed significantly reduced mNSS score and brain tissue water content (9.83±1.17 vs. 7.66±1.21; [83.62±0.91]% vs. [80.09±0.68]%, P<0.05). HE staining indicated clearer structure of the cortical area at the injury sites, and improved neuron morphology in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group; and transmission electron microscopy showed reduced mitochondrial shrinkage and partial restoration of cristae structures in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group. Compared with the TBI+vehicle group, the TBI+SIRT1 agonist group exhibited significantly decreased MDA content ([62.72±9.20] nmol/g vs. [39.34±3.48] nmol/g), increased SOD activity ([1.95±0.23] U/mg vs. [2.48±0.14] U/mg), elevated GPX4 protein expression (0.37±0.04 vs. 0.46±0.03), and decreased HIF-1α and ACSL4 protein expressions (1.16±0.15 vs. 0.81±0.12; 1.14±0.06 vs. 1.29±0.04), with significant differences ( P<0.05). Conclusion:SIRT1 activation can exert neuroprotective effect by inhibiting HIF-1α-mediated glycolysis and reducing neuronal ferroptosis after TBI.

Objective:Explore the protective effect and mechanism of methyl badosolone (CDDO-Me) on rats with traumatic brain injury (TBI).Methods:A total of 72 SPF-grade SD rats aged 8 weeks were randomly (random number) divided into 4 groups ( n=18) using the random number table method: Sham, TBI, TBI+Vehicle, and TBI+CDDO-Me. The rat TBI model was established using the hydraulic impact head injury method. The TBI+CDDO-Me group was administered CDDO-Me (dissolved in 1% DMSO, at a dose of 10 mg/kg) via intraperitoneal injection 30 minutes after modeling, twice a day for a total of 3 days. On the third day after modeling, brain tissue was collected for pathological and water content detection after mNSS scoring. Immunofluorescence double staining was used to detect the expression of nuclear factor erythroid2 related factor 2 (Nrf2); immunohistochemical staining was used to detect the expression of ionized calcium binding adapter molecule-1(Iba-1); ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1β, and IL-18 in serum; kits were used to detect the levels of malondialdehyde (MDA) and reactive oxygen species (ROS); Western blot was used to detect the expression of the Nrf2 pathway, B-cell lymphoma-2 (BCL-2), and BCL-2 associated X protein (BAX). Results:(1) Compared with the Sham group, the mNSS scores and water content in the injured cortex of the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05). (2) Compared with the Sham group, the proportion of Nissl-stained injured neurons and apoptotic positive cells in the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05), accompanied by a decrease in BAX protein expression and upregulation of BCL-2 protein expression (both P<0.05). (3) Immunofluorescence and Western blot results showed that compared with the Sham group, the expression of total Nrf2, nuclear Nrf2, HO-1, and NQO1 proteins in the TBI group were all increased (all P<0.05), and the increase was more significant after CDDO-Me intervention (all P<0.05). (4) Immunohistochemistry and ELISA results showed that compared with the Sham group, the levels of MDA, ROS, Iba-1 in brain tissue and the levels of TNF-α, IL-1β, and IL-18 in serum in the TBI group rats were all significantly increased (all P<0.05), and all significantly decreased after CDDO-Me intervention (all P<0.05). Conclusion:CDDO-Me helps to reduce oxidative stress and inflammatory responses in TBI rats, and the mechanism may be related to the activation of the Nrf2/HO-1 antioxidant stress pathway.

Objective To explore the feasibility and safety of non-anticoagulation veno-venous extracorporeal membrane oxygenation(VV-ECMO)in patients with severe chest trauma.Methods A retrospective cohort study method was used.A total of 19 patients with severe chest trauma who received VV-ECMO with a delayed anticoagulation strategy at Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to October 2021 were included in the delayed anticoagulation group,and 20 patients with severe chest trauma who received VV-ECMO with a non-anticoagulation strategy from November 2021 to October 2024 were included in the non-anticoagulation group.The overall clinical characteristics of the patients were statistically analyzed,including gender,age,injury severity score(ISS),acute physiology and chronic health evaluationⅡ(APACHEⅡ),reason for VV-ECMO,use of vasoactive drugs,oxygenation index(PaO2/FiO2),and interval from injury to VV-ECMO.The primary outcomes were hemorrhagic and thrombotic complications.The secondary outcomes were blood transfusion during VV-ECMO,VV-ECMO time,mechanical ventilation time,intensive care unit(ICU)length of stay,and 28-day mortality.Results There was no significant difference in gender,age,ISS score,APACHEⅡscore,reason for VV-ECMO,use of vasoactive drugs,PaO2/FiO2,and interval from injury to VV-ECMO between the non-anticoagulation group and the delayed anticoagulation group.There was no significant difference in overall incidence of hemorrhagic and thrombotic between the two groups[incidence of hemorrhagic complications:15.0%(3/20)vs.31.6%(6/19),incidence of thrombotic:15.0%(3/20)vs.5.3%(1/19),both P>0.05].The infusion rate of 4 or more paked red blood cell(PRBC)within 24 hours during VV-ECMO in the non-anticoagulation group was significantly lower than that in the delayed anticoagulation group[5.0%(1/20)vs.31.6%(6/19),P<0.05].The amount of PRBC and platelet transfusion and the time on VV-ECMO in the non-anticoagulation group during VV-ECMO were significantly lower than those in the delayed anticoagulation group[PRBC(U):5.8±3.8 vs.8.1±3.1,platelets(U):1(0,1)vs.2(1,3),time on VV-ECMO(hours):71.55±24.37 vs.114.21±34.08,all P<0.05].There were no statistically significant differences in the amount of plasma and cryoprecipitate transfusion during VV-ECMO,mechanical ventilation time,ICU hospitalization time,and 28-day mortality between the two groups.Conclusion For patients with severe chest trauma receiving VV-ECMO withholding routine systemic anticoagulation did not result in thrombotic complications or higher mortality and required less PRBC and platelet transfusions.Non-anticoagulant VV-ECMO is safe and feasible for patients with severe chest trauma with high risk of bleeding.

Objective To explore the feasibility and safety of non-anticoagulation veno-venous extracorporeal membrane oxygenation(VV-ECMO)in patients with severe chest trauma.Methods A retrospective cohort study method was used.A total of 19 patients with severe chest trauma who received VV-ECMO with a delayed anticoagulation strategy at Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to October 2021 were included in the delayed anticoagulation group,and 20 patients with severe chest trauma who received VV-ECMO with a non-anticoagulation strategy from November 2021 to October 2024 were included in the non-anticoagulation group.The overall clinical characteristics of the patients were statistically analyzed,including gender,age,injury severity score(ISS),acute physiology and chronic health evaluationⅡ(APACHEⅡ),reason for VV-ECMO,use of vasoactive drugs,oxygenation index(PaO2/FiO2),and interval from injury to VV-ECMO.The primary outcomes were hemorrhagic and thrombotic complications.The secondary outcomes were blood transfusion during VV-ECMO,VV-ECMO time,mechanical ventilation time,intensive care unit(ICU)length of stay,and 28-day mortality.Results There was no significant difference in gender,age,ISS score,APACHEⅡscore,reason for VV-ECMO,use of vasoactive drugs,PaO2/FiO2,and interval from injury to VV-ECMO between the non-anticoagulation group and the delayed anticoagulation group.There was no significant difference in overall incidence of hemorrhagic and thrombotic between the two groups[incidence of hemorrhagic complications:15.0%(3/20)vs.31.6%(6/19),incidence of thrombotic:15.0%(3/20)vs.5.3%(1/19),both P>0.05].The infusion rate of 4 or more paked red blood cell(PRBC)within 24 hours during VV-ECMO in the non-anticoagulation group was significantly lower than that in the delayed anticoagulation group[5.0%(1/20)vs.31.6%(6/19),P<0.05].The amount of PRBC and platelet transfusion and the time on VV-ECMO in the non-anticoagulation group during VV-ECMO were significantly lower than those in the delayed anticoagulation group[PRBC(U):5.8±3.8 vs.8.1±3.1,platelets(U):1(0,1)vs.2(1,3),time on VV-ECMO(hours):71.55±24.37 vs.114.21±34.08,all P<0.05].There were no statistically significant differences in the amount of plasma and cryoprecipitate transfusion during VV-ECMO,mechanical ventilation time,ICU hospitalization time,and 28-day mortality between the two groups.Conclusion For patients with severe chest trauma receiving VV-ECMO withholding routine systemic anticoagulation did not result in thrombotic complications or higher mortality and required less PRBC and platelet transfusions.Non-anticoagulant VV-ECMO is safe and feasible for patients with severe chest trauma with high risk of bleeding.

Objective:To preliminarily explore whether sirtuin1 (SIRT1) activation can inhibit neuronal ferroptosis in rats after traumatic brain injury (TBI) by regulating hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis.Methods:(1) Six SD rats were randomly divided into sham-operated group and TBI group, with 3 rats in each group; TBI model in the TBI group was established by hydraulic impact method, and rats in the sham-operated group underwent same surgery without impact. Cortical tissues of the two groups were sent for tandem mass tag (TMT) labeled quantitative proteomics detection to analyze the differential expression proteome; Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to detect pathway enrichment of the screened differential proteins. (2) Twelve SD rats were randomly divided into sham-operated group and 1-day, 3-day and 7-day post-TBI groups, with 3 rats in each group. Treatment methods were the same as above; Western blotting was used to detect SIRT1 protein expression. (3) Forty-eight rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+SIRT1 agonist group, with 12 rats in each group; rats in the sham-operated group and TBI group accepted treatment as above; rats in the TBI+SIRT1 agonist group were intraperitoneally injected with SRT1720 (dissolved in ≤ 5% dimethyl sulfoxide, at a dose of 20 mg/kg) within 30 minutes after modeling, twice a day (with an interval of 12 hours); and rats in the TBI+vehicle group were injected with same dose of dimethyl sulfoxide at the same time. One d after modeling, neurological deficit was assessed using modified Neurological severity score (mNSS), brain water content was measured by dry-wet weight method, histopathological changes in the cortical lesions were observed by HE staining, mitochondrial ultrastructure was examined by transmission electron microscopy, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the brain tissues were detected by colorimetry, and protein expressions of SIRT1, HIF-1α (key protein in the glycolytic pathway), glutathione peroxidase 4 (GPX4, key protein in the ferroptosis pathway), and acyl-CoA synthetase long-chain family member 4 (ACSL4, key protein in the ferroptosis pathway) were evaluated by Western blotting.Results:(1) KEGG analysis revealed that the glycolysis pathway and HIF-1 signaling pathway were obviously enriched in the cortical tissues of rats in the TBI group compared with the sham-operated group; GSEA showed that the HIF-1 signaling pathway (mmu04066) and ferroptosis pathway (mmu04216) gene sets in the cortical tissues of rats in the TBI group exhibited enrichment trends compared with those in the sham-operated group. (2) Compared with the sham-operated group, the 1-day, 3-day, and 7-day post-TBI groups had significantly decreased SIRT1 protein expression ( P<0.05), with the most prominent decline in 1-day post-TBI group. (3) Compared with the TBI+vehicle group, rats in the TBI+SIRT1 agonist group showed significantly reduced mNSS score and brain tissue water content (9.83±1.17 vs. 7.66±1.21; [83.62±0.91]% vs. [80.09±0.68]%, P<0.05). HE staining indicated clearer structure of the cortical area at the injury sites, and improved neuron morphology in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group; and transmission electron microscopy showed reduced mitochondrial shrinkage and partial restoration of cristae structures in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group. Compared with the TBI+vehicle group, the TBI+SIRT1 agonist group exhibited significantly decreased MDA content ([62.72±9.20] nmol/g vs. [39.34±3.48] nmol/g), increased SOD activity ([1.95±0.23] U/mg vs. [2.48±0.14] U/mg), elevated GPX4 protein expression (0.37±0.04 vs. 0.46±0.03), and decreased HIF-1α and ACSL4 protein expressions (1.16±0.15 vs. 0.81±0.12; 1.14±0.06 vs. 1.29±0.04), with significant differences ( P<0.05). Conclusion:SIRT1 activation can exert neuroprotective effect by inhibiting HIF-1α-mediated glycolysis and reducing neuronal ferroptosis after TBI.

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.
Humans ; Electroacupuncture ; Ischemic Stroke ; Learning ; Signal Transduction/physiology*

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Aim To establish three kinds of DNA damage models of mouse testicular spermatogonia cell line GC-1 cells and analyze their similarities and differences. Methods GC-1 cells were treated with UVB irradiation, D-galactose(D-Gal) or bleomycin (BLM), respectively. Then the expression and localization of 'Y-H2AX were detected by Western blot and immunofluorescence, the expression and localization of 8-OHdG were measured by immunofluorescence, and the expression levels of p-p53 and p21 were measured by Western blot. Results The expression of -y-H2AX in GC-1 cell reached to the peak 4 h after UVB irradiation and 6 h after D-Gal stimulation, whereas -y-H2AX expression gradually increased after BLM stimulation, and the higher the concentration of BLM,the shorter the time to reach the peak. The results of immunofluorescence showed that 8-OHdG expression was observed in the nucleus and cytoplasm of GC-1 cells after UVB irradiation and BLM stimulation, and the longer the culture time, the more the expression in the nucleus. In contrast, the expression of 8-OHdG was observed in the cytoplasm and reached the peak at 6 h in the D-Gal stimulated GC-1 cells. After UVB irradiation, the protein expression levels of p-p53 gradually increased, while p21 protein expression appeared later than that of p-p53; in the D-Gal stimulated GC-1 cells, the protein expression levels of p-p53 reached the peak at 6 h, and p21 protein expression reached the peak at 12 h; after low concentration BLM stimulation, the protein expression levels of p-p53 and p21 continuously increased, and after high concentration BLM stimulation, the protein expression levels of p-p53 and p21 reached its peak at 2 h, then decreased at 4 h. Conclusions Three kinds of DNA damage models of GC-1 cells are successfully established, and the DNA damage in GC-1 cells treated with D-Gal is mild, while the DNA damage in GC-1 cells treated by UVB irradiation and BLM stimulation is more severe.