ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×10¹¹ particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe²⁺), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe²⁺ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.

Objective To understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

Objective:To analyze risk factors for early trauma-induced coagulopathy (TIC) in pediatric patients with moderate-to-severe traumatic brain injury (msTBI), develop a predictive model and evaluate its predictive performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 290 pediatric patients with msTBI who were admitted to Children′s Hospital of Soochow University between January 2016 and December 2024, including 188 boys and 102 girls, aged 0.2-15.7 years [5.2(2.8, 9.3)years]. Based on the coagulation test results at admission, the patients were divided into TIC group ( n=162) and non-TIC group ( n=128). The patients were randomly allocated into training set ( n=203) and validation set ( n=87) at a ratio of 7∶3. Demographic characteristics, clinical data, vital signs, imaging findings, arterial blood gas analysis results, and coagulation profiles of the patients were collected. Univariate analysis and Lasso regression analysis were used to identify risk factors associated with early TIC in children with msTBI and multivariate Logistic regression analysis was performed to determine independent risk factors and construct a predictive model. The model′s discrimination and calibration were evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), Hosmer-Lemeshow (H-L) test, and calibration curve. Its clinical utility was assessed through decision curve analysis (DCA). Results:Significant differences were observed between the TIC group and non-TIC group in terms of age, weight, time from injury to admission, child′s Glasgow coma scale (CGCS) score, pediatric trauma score (PTS), shock index, heart rate, respiratory rate, systolic blood pressure, Rotterdam CT score, intraventricular hemorrhage, cerebral contusion, brain herniation, long bone fracture, pelvic fracture, hemopneumothorax, pulmonary contusion, intra-abdominal organ injury, actual bicarbonate, base excess, base excess in the extracellular fluid, blood glucose, hemoglobin (Hb), osmolarity, blood calcium, anion gap, blood lactate, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelet count ( P<0.05). With coagulation-related variables excluded, the following features were identified with Lasso regression including CGCS score, PTS, heart rate, systolic blood pressure, long bone fracture, blood glucose, and Hb. Multivariate Logistic regression analysis revealed that CGCS score≤8 points ( OR=3.05, 95% CI 1.65, 5.63), PTS>5 points ( OR=0.45, 95% CI 0.23, 0.89), systolic blood pressure ( OR=0.98, 95% CI 0.97, 0.99), blood glucose ( OR=1.09, 95% CI 1.01, 1.17), and long bone fracture ( OR=2.47, 95% CI 1.13, 5.42) were influencing factors for early TIC in children with msTBI ( P<0.05). The regression equation of the predictive model was established as follows: Logit[ P/(1- P)]=1.01×"CGCS score≤8 points"-0.69×"PTS>5 points"- 0.02×"systolic blood pressure"+0.89×"long bone fracture"+0.08×"blood glucose"+1.32. The ROC curve analysis showed that the training set had an AUC of 0.86 (95% CI 0.78, 0.94), with sensitivity and specificity of 76.6% and 92.5%, while the AUC was 0.80 (95% CI 0.74, 0.86), with sensitivity and specificity of 75.7% and 79.6% in the validation set. H-L test results showed a χ2 value of 8.18 ( P=0.416) in the training set and 5.30 ( P=0.216) in the validation set. The calibration curves for both sets demonstrated good agreement with the actual curves, indicating that the predicted probabilities closely matched the observed probabilities. The DCA results indicated that both the training set and validation set demonstrated positive net benefits within threshold probabilities ranges of 10%-100% and 15%-96%. Conclusions:Independent risk factors for early TIC in pediatric msTBI patients include CGCS score≤ 8 points, PTS≤5 points, low systolic blood pressure, long bone fracture, and high blood glucose. The predictive model constructed based on these factors demonstrates favorable predictive performance and clinical application value.

BACKGROUND:Bone morphogenetic protein 2 is vital in embryonic development,bone formation,and regeneration,but its high-dose application is linked to cancer.Bone morphogenetic protein 2 osteogenic peptide L20 reduces adverse effects like cancer and boosts bone tissue regeneration.OBJECTIVE:To graft bone morphogenetic protein 2 active peptide segments onto mesopores and surfaces through a peptide mimicry strategy inspired by oysters,and explore its impact on osteogenic properties of tissue-engineered bone.METHODS:(1)Mesoporous bioactive glass was synthesized using a template method.Bone morphogenetic protein 2 osteogenic peptide L20 was loaded onto mesoporous bioactive glass using a one-step synthesis method to characterize the morphology and in vitro sustained release properties of mesoporous active glass nanoparticles loaded with bone morphogenetic protein 2 osteogenic active peptide L20.(2)Bone marrow mesenchymal stem cells were isolated and extracted from SD rats.After two generations,they were co-cultured with PBS(blank group),mesoporous bioactive glass nanoparticles(control group),and mesoporous bioactive glass nanoparticles loaded with bone morphogenetic protein 2 osteogenic active peptide L20(experimental group).Cell live/dead fluorescence staining and CCK-8 assay were used to detect cytotoxicity and cell proliferation.Scanning electron microscopy was used to observe cell adhesion.After osteogenic induction and differentiation,alkaline phosphatase staining,Alizarin red S staining,and osteogenesis-related gene expression were detected.(3)Fifteen SD rats were selected to establish bilateral femoral condyle defect models and divided into three groups using a random number table method:the blank group(n=5)was not implanted with any material;the control group(n=5)was implanted with mesoporous bioactive glass nanoparticles,and the experimental group(n=5)was implanted with mesoporous bioactive glass nanoparticles loaded with bone morphogenetic protein 2 osteogenic active peptide L20.Eight weeks after surgery,femoral Micro-CT scanning and tissue morphology observation were performed.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the mesoporous bioactive glass nanoparticles loaded with bone morphogenetic protein 2 osteogenic active peptide L20 were spherical and monodisperse particles.Transmission electron microscopy showed their porous structure with an average particle size of(268.10±0.58)nm,which could release L20 in vitro.(2)Mesoporous bioglass nanoparticles loaded with bone morphogenetic protein 2 osteogenic active peptide L20 were non-cytotoxic and could promote the proliferation and adhesion of bone marrow mesenchymal stem cells.Compared with the blank group and the control group,the alkaline phosphatase activity and extracellular matrix mineralization capacity of the experimental group were increased(P<0.05),and the mRNA expression levels of alkaline phosphatase,Runx2,and osteocalcin were increased(P<0.05).(3)The results of femoral Micro-CT scanning showed that compared with the blank group and the control group,the new bone mass and bone density of the experimental group were increased(P<0.05).The results of hematoxylin-eosin and Masson staining showed that compared with the blank group and the control group,the new bone formation and collagen fibers of the experimental group were increased.(4)These findings indicate that mesoporous bioactive glass loaded with bone morphogenetic protein 2 active peptide L20 exhibits excellent biocompatibility and in vitro and in vivo osteogenic properties,promoting regeneration and repair of SD rat femoral condyle defects.

Objective To systematically explore the prescription source,prescription composition,drug origin and processing,functional indications and clinical application of the classic Tibetan medicine Sanwei Qiangwei Powder,so as to provide scientific basis for its in-depth development,rational utilization and follow-up research.Methods By using methods of literature review,the ancient and modern Tibetan medical classics and modern literature such as'Ocha Jinmai' sporadic secret collection 'Zhigong Yi Suan Ji' were retrieved,and the prescription origin,medicinal material origin,processing technology,prescription solution,usage and dosage were studied and analyzed.Results The Sanwei Qiangwei Powder originated from the 'Ocha Jinmai'(《()》)written by Qiangba Minimatongwatundan in the 15th century.The book was written much earlier than the literature included in the 'Catalogue of Ancient Classic Prescriptions(Second Batch)'-the 'Selection of Tibetan Medicine Prescriptions·Longevity Baoru' in the 19th century.The prescription consists of 15 copies of Rosa rugosa,7 copies of Herpetospermum caudigerum,and 3 copies of Terminalia chebula Retz.It plays a significant effect on hepatobiliary diseases such as biliary fever,liver fever,primary headache,and headache after drinking in clinical practice.It is the core prescription for the treatment of Chiba-type diseases and has high development value.There are differences in the use site,dosage ratio,usage and dosage of medicinal materials in different literatures,and the dosage has been clarified by textual research and expert consultation.Conclusion This study sorted out and clarified the key information of Sanwei Qiangwei Powder,which laid a theoretical foundation for the inheritance and development,innovative application and modernization research of the prescription.

AIM:To investigate the antitumor activity and targets of baicalein(Bai)in pancreatic cancer using network pharmacology combined with in vitro and in vivo experiments.METHODS:The targets of Bai and pancreatic can-cer were analyzed via multi-data screening.A protein-protein interaction network was constructed using STRING,and core targets were identified via Cytoscape.Functional enrichment was analyzed by Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG).Antitumor effects of Bai were assessed in pancreatic cancer cells Aspc-1 and Bxpc-3 using MTT and colony formation assays for proliferation,flow cytometry for apoptosis and cell cycle analysis,and Transwell assays for migration and invasion.A xenograft tumor model was established to evaluate tumor proliferation,im-munohistochemistry was performed to detect the protein expression of AKT in tumor tissues,and Western blot was used to analyze the expression levels of AKT,β-catenin,N-cadherin and Slug.RESULTS:A total of 108 overlapping targets were identified between Bai and pancreatic cancer.Among these,7 core targets were recognized,including proto-onco-gene tyrosine-protein kinase Src,heat shock protein 90 alpha family class A member 1(HSP90AA1),estrogen receptor 1(ESR1),tumor protein p53(TP53),epidermal growth factor receptor(EGFR),AKT1,and mitogen-activated protein ki-nase 3(MAPK3).The GO analysis revealed significant enrichment in oxidative stress response,protein phosphorylation,and serine/threonine kinase activity.The KEGG analysis primarily enriched the PI3K/AKT,MAPK and Ras signaling pathways.The MTT and colony formation assays showed that Bai inhibited the viability of Aspc-1 and Bxpc-3 cells in a dose-dependent manner(72 h IC50 values were 73.6 μmol/L and 83.4 μmol/L,respectively)and reduced cell colony for-mation(P<0.05 or P<0.01).Flow cytometry confirmed that Bai induced apoptosis of Aspc-1 and Bxpc-3 cells(P<0.01)and blocked the cell cycle at the G0/G1 phase(P<0.05 or P<0.01).Transwell experiments indicated that Bai inhibited the migration and invasion of Aspc-1 and Bxpc-3 cells(P<0.05 or P<0.01).In vivo,Bai significantly inhibited the growth of Aspc-1 cell xenograft tumors(P<0.01).Immunohistochemistry revealed a significant reduction in AKT expression in tu-mor tissues(P<0.01),and Western blot showed decreased expression of AKT,β-catenin,N-cadherin and Slug in both Aspc-1 and Bxpc-3 cells(P<0.01).CONCLUSION:Baicalein inhibits pancreatic cancer cell proliferation,migration,and invasion,potentially through down-regulation of AKT,β-catenin,N-cadherin,and Slug expression.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To analyze risk factors for early trauma-induced coagulopathy (TIC) in pediatric patients with moderate-to-severe traumatic brain injury (msTBI), develop a predictive model and evaluate its predictive performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 290 pediatric patients with msTBI who were admitted to Children′s Hospital of Soochow University between January 2016 and December 2024, including 188 boys and 102 girls, aged 0.2-15.7 years [5.2(2.8, 9.3)years]. Based on the coagulation test results at admission, the patients were divided into TIC group ( n=162) and non-TIC group ( n=128). The patients were randomly allocated into training set ( n=203) and validation set ( n=87) at a ratio of 7∶3. Demographic characteristics, clinical data, vital signs, imaging findings, arterial blood gas analysis results, and coagulation profiles of the patients were collected. Univariate analysis and Lasso regression analysis were used to identify risk factors associated with early TIC in children with msTBI and multivariate Logistic regression analysis was performed to determine independent risk factors and construct a predictive model. The model′s discrimination and calibration were evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), Hosmer-Lemeshow (H-L) test, and calibration curve. Its clinical utility was assessed through decision curve analysis (DCA). Results:Significant differences were observed between the TIC group and non-TIC group in terms of age, weight, time from injury to admission, child′s Glasgow coma scale (CGCS) score, pediatric trauma score (PTS), shock index, heart rate, respiratory rate, systolic blood pressure, Rotterdam CT score, intraventricular hemorrhage, cerebral contusion, brain herniation, long bone fracture, pelvic fracture, hemopneumothorax, pulmonary contusion, intra-abdominal organ injury, actual bicarbonate, base excess, base excess in the extracellular fluid, blood glucose, hemoglobin (Hb), osmolarity, blood calcium, anion gap, blood lactate, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelet count ( P<0.05). With coagulation-related variables excluded, the following features were identified with Lasso regression including CGCS score, PTS, heart rate, systolic blood pressure, long bone fracture, blood glucose, and Hb. Multivariate Logistic regression analysis revealed that CGCS score≤8 points ( OR=3.05, 95% CI 1.65, 5.63), PTS>5 points ( OR=0.45, 95% CI 0.23, 0.89), systolic blood pressure ( OR=0.98, 95% CI 0.97, 0.99), blood glucose ( OR=1.09, 95% CI 1.01, 1.17), and long bone fracture ( OR=2.47, 95% CI 1.13, 5.42) were influencing factors for early TIC in children with msTBI ( P<0.05). The regression equation of the predictive model was established as follows: Logit[ P/(1- P)]=1.01×"CGCS score≤8 points"-0.69×"PTS>5 points"- 0.02×"systolic blood pressure"+0.89×"long bone fracture"+0.08×"blood glucose"+1.32. The ROC curve analysis showed that the training set had an AUC of 0.86 (95% CI 0.78, 0.94), with sensitivity and specificity of 76.6% and 92.5%, while the AUC was 0.80 (95% CI 0.74, 0.86), with sensitivity and specificity of 75.7% and 79.6% in the validation set. H-L test results showed a χ2 value of 8.18 ( P=0.416) in the training set and 5.30 ( P=0.216) in the validation set. The calibration curves for both sets demonstrated good agreement with the actual curves, indicating that the predicted probabilities closely matched the observed probabilities. The DCA results indicated that both the training set and validation set demonstrated positive net benefits within threshold probabilities ranges of 10%-100% and 15%-96%. Conclusions:Independent risk factors for early TIC in pediatric msTBI patients include CGCS score≤ 8 points, PTS≤5 points, low systolic blood pressure, long bone fracture, and high blood glucose. The predictive model constructed based on these factors demonstrates favorable predictive performance and clinical application value.