Objective To construct a targeted drug delivery system, Ang-BEVs@Dox, based on Angiopep-2 peptide-modified bacterial extracellular vesicles （BEVs） loaded with doxorubicin （Dox）, overcome the challenges of blood-brain barrier （BBB） penetration and systemic toxicity in chemotherapy for glioblastoma （GBM）, enhance drug targeting to brain tumors and reduce its toxic side effects. Methods BEVs derived from Escherichia coli were isolated using ultracentrifugation. The targeting ligand Angiopep-2, specific for the LRP-1 receptor, was conjugated onto the surface of BEVs to construct the targeted carrier （Ang-BEVs）. Dox was loaded into Ang-BEVs using low-frequency sonication to form Ang-BEVs@Dox. The physicochemical properties （morphology and size） of the carriers were characterized by transmission electron microscopy （TEM） and dynamic light scattering （DLS）. The BBB-penetrating capability, in vitro/in vivo anti-tumor efficacy, and biosafety of the system were evaluated using cellular uptake assays, 3D tumor spheroid models, and orthotopic tumor-bearing mouse models. Results ① Carrier characterization and in vitro efficacy: Ang-BEVs@Dox exhibited a particle size of approximately 100 nm and maintained structural stability after Dox loading. It significantly enhanced cellular uptake efficiency in U87MG cells and achieved deep penetration within 3D tumor spheroids. Cytotoxicity assays demonstrated synergistic anti-tumor effects between the BEVs and Dox in the Ang-BEVs@Dox system. ② In vivo targeting and anti-tumor efficacy: In orthotopic tumor-bearing mouse models, Ang-BEVs@Dox effectively penetrated the BBB and significantly inhibited tumor growth, extending the median survival time of tumor-bearing mice to 33.5 days （compared to 23.5 days in the blank control group, P<0.001）. Immunohistochemical analysis revealed significant suppression of the tumor cell proliferation marker Ki-67 and enhancement of the apoptosis marker TUNEL staining signals. ③ Biosafety: Major organs from mice in the Ang-BEVs@Dox treatment group showed no observable pathological damage, indicating good biosafety. Conclusion This study successfully constructed an Angiopep-2 peptide-modified engineered BEVs delivery system （Ang-BEVs@Dox）. Through Angiopep-2-mediated BBB penetration and tumor targeting, it significantly enhanced the accumulation and therapeutic efficacy of BEVs at the GBM site. This method combined efficient delivery, low systemic toxicity, and clinical translation potential, which provided an innovative solution to overcome the therapeutic bottleneck in GBM treatment.

Objective     To explore the efficacy of prone positioning ventilation in patients with acute respiratory distress syndrome (ARDS) after acute Stanford type A aortic dissection (STAAD) surgery. Methods     From November 2019 to September 2021, patients with ARDS who was placed prone position after STAAD surgery in the Xiamen Cardiovascular Hospital of Xiamen University were collected. Data such as the changes of blood gas, respiratory mechanics and hemodynamic indexes before and after prone positioning, complications and prognosis were collected for statistical analysis. Results    A total of 264 STAAD patients had surgical treatment, of whom 40 patients with postoperative ARDS were placed prone position. There were 37 males and 3 females with an average age of 49.88±11.46 years. The oxygen partial pressure, oxygenation index and peripheral blood oxygen saturation 4 hours and 12 hours after the prone positioning, and 2 hours and 6 hours after the end of the prone positioning were significantly improved compared with those before prone positioning ventilation (P<0.05). The oxygenation index 2 hours after the end of prone positioning which was less than 131.42 mm Hg, indicated that the patient might need ventilation two or more times of prone position. Conclusion     Prone position ventilation for patients with moderate to severe ARDS after STAAD surgery is a safe and effective way to improve the oxygenation.

Objective To exploring the correlation between serum miR-195 and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients.Methods A total of 79 patients with T2DM who were treated in the Endocrinology Department of Gansu Provincial People's Hospital were enrolled in this study from October 2022 to August 2023.They were divided into simple T2DM(n=37)and MAFLD group(MAFLD,n=42)according to whether they were complicated with MAFLD.Meanwhile,34 healthy individuals who underwent physical examinations were selected as the normal control(NC)group.Results Compared with the NC group,FPG,HbA1c and HOMA-IR increased,while HDL-C decreased in T2DM and MAFLD group(P<0.05).The TG and hs-CRP levels were higher in MAFLD group than in NC and T2DM group(P<0.05).The serum miR-195 expression decreased sequentially(P<0.05),while FAS increased sequentially in NC,T2DM,and MAFLD group(P<0.05).Spearman correlation analysis showed that miR-195 was negatively correlated with FPG,HOMA-IR,hs-CRP,and FAS(P<0.05).Multiple linear regression analysis showed that HOMA-IR and FAS were the influencing factors for serum miR-195.Conclusions Down-regulation of serum miR-195 expression in patients with T2DM combined with MAFLD may be by glucose and lipid metabolism,IR and inflammatory response.

To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.
Animals ; Mice ; Brain Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Feedback ; Gene Expression Regulation, Neoplastic ; Glioblastoma/metabolism* ; MicroRNAs/metabolism* ; Temozolomide/therapeutic use* ; Humans ; Forkhead Box Protein O1/metabolism*

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Traumatic intracranial hematoma progresses rapidly and may cause quick increase of intracranial pressure and even brain hernia, ultimately leading to coma or death. Therefore, traumatic intracranial hematoma needs prompt treatment, but the prerequisite of treatment is early examination and diagnosis. Due to the limited transportation and other reasons, the existing large-scale detection devices such as CT and MRI cannot be deployed on the rescue site or during patient transportation. Instead, the portable diagnosis devices have the characteristics of miniaturization and high flexibility, which is conducive to promoting early detection, assisting diagnosis and further guiding the formulation of treatment plans. At present, more and more attention has been paid to the portable diagnosis devices in the diagnosis of intracranial hematoma. The authors summarized the conventional diagnosis methods and application of portable diagnosis devices for traumatic intracranial hematoma, aiming to provide a reference for the diagnosis of traumatic intracranial hematoma.

Objective:To investigate the changes of plasma prothrombin fragment 1+ 2 (F 1+2), tissue factor positive microparticle (TF+ MP) and thrombin antithrombin complex (TAT) level before and after the treatment of low molecular weight heparin combined with reteplase in patients with malignant tumor and lower extremity venous thrombosis. Methods:From July 2016 to October 2019, 64 patients with malignant tumors and lower extremity venous thrombosis in the Third Hospital of Changsha were selected, they were divided into observation group ( n=32) and control group ( n=32) by simple randomization. The control group was treated with low molecular heparin, and the observation group was treated with low molecular heparin combined with reteplase. The efficacy, clinical symptom improvement time, incidence of adverse reactions, difference in lower limb circumference, blood flow velocity, activated partial thromboplastin time (APTT), prothrombin time (PT), plasma F 1+2, TF+ MP, TAT level before and after treatment were compared between the two groups; the correlations of plasma F 1+2, TF+ MP, and TAT level with clinical symptom improvement time, peripheral diameter difference of lower extremity, blood flow velocity, APTT, and PT were analyzed. Results:The total effective rate of the observation group (87.50%) was higher than that of the control group (65.63%) ( P<0.05); The improvement time of clinical symptoms in the observation group was shorter than that in the control group ( P<0.05); After treatment, the peripheral limb diameter difference of the observation group was lower than that of the control group, and the blood flow velocity was higher than that of the control group ( P<0.05); The APTT and PT in the observation group were higher than those in the control group after treatment ( P<0.05); The plasma F 1+2, TF+ MP, and TAT level in the observation group were lower than those in the control group after treatment ( P<0.05); The levels of plasma F 1+2, TF+ MP, and TAT were positively correlated with symptom improvement time and lower limb circumference difference, and negatively correlated with blood flow velocity, APTT, and PT ( P<0.05); There was no significant difference in the incidence of adverse reactions (18.75%) between the observation group and the control group (12.50%) during the treatment period ( P>0.05). Conclusions:Plasma F 1+2, TF+ MP, and TAT expression in patients with malignant tumors and venous thrombosis of the lower extremity can be used as biological indicators to evaluate the patient's condition and treatment effect. Low molecular weight heparin combined with reteplase can significantly reduce the plasma F 1+2, TF+ MP and TAT level, promote the improvement of symptoms, effectively reduce the peripheral diameter difference of lower extremity, improve blood flow velocity and coagulation function, and has a significant effect.

OBJECTIVE: To explore the relationship between shift work and type 2 diabetes in oil workers. METHODS: A total of 2 666 oil workers in an oil group were selected as the study subjects using the typical sampling method. Questionnaire survey was conducted by a self-designed Questionnaire of Health Assessment for Oil Workers, and blood glucose level was measure. RESULTS: The prevalence of type 2 diabetes in the study subjects was 10.1%(268/2 666). The prevalence of type 2 diabetes in shift workers was higher than that in non-shift workers(13.1% vs 6.0%, P<0.01). After adjusting for the influence of confounding factors such as gender, body mass index, family history of diabetes, history of hypertension, history of hyperlipidemia, and physical exercise, multivariate logistic regression analysis results show that the longer the shift work length, the higher the risk of developing type 2 diabetes(P<0.01), workers with shift work(3 shifts in a day, 2 shifts operating) had a higher risk of type 2 diabetes than that in non-shift workers(P<0.05). CONCLUSION: The shift work length and shift workers with 3 shifts in a day, 2 shifts operating can increase the risk of type 2 diabetes in oil workers.

OBJECTIVE: To explore the effect of occupational high temperature exposure on type 2 diabetes( T2 DM) in male steel workers. METHODS: A cluster random sampling method was used to select 684 male steel workers,who exposed to occupational high temperature in a steel enterprise in Tangshan City,as the high temperature group,and 1 153 male steel workers without occupational high temperature exposure as the control group. The high temperature level of workers in these two groups was measured. The cumulative exposure( CE) of high temperature was calculated,and occupational health exam was performed. The multivariate logistic regression analysis and restricted cubic splines were used to analyze the relationship between high temperature CE and T2 DM. RESULTS: The prevalence of T2 DM in high-temperature group was higher than that in the control group( 13. 0% vs 7. 9%,P < 0. 05). The multivariate logistic regression analysis results showed that the risk of T2 DM in the high temperature group was higher than that in the control group after adjusting for age,body mass index,smoking,drinking,physical exercise and parents with diabetes( P < 0. 05). The 95% confidence interval was 1. 65( 1. 17-2. 33). Restricted cubic spline analysis showed that the high temperature CE was correlated with the prevalence of T2 DM in workers( P < 0. 01) and showed a linear correlation( nonlinearity test,P > 0. 05). CONCLUSION: Occupational high temperature exposure is associated with the occurrence of T2 DM in male steel workers. The male steel workers with high temperature CE show high prevalence of T2 DM risk.

Objective: To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF. Methods: We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis. Results: (1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation. Conclusions The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.