Objective:To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock,and to clarify its mechanism.Methods:A total of 54 healthy adult SD rats were randomly divided into normal group,blast injury complicated with hemorrhagic shock(model)group,and the fluid resuscitation(treatment)group,and there were 18 rats in each group.Among them,10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes.The average survival time(ST),24 h and 72 h survival rates of the rats in various groups were observed;the blood pressure(BP),heart rate(HR),and respiratory rate(RR)of the rats in various groups were observed;the levels of serum creatinine(Scr),blood urea nitrogen(BUN),lactate(LAC),glucose(GLU),iron ions,glutathione(GSH),and malondialdehyde(MDA)and the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in serum of the rats in various groups were detected;Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and heme oxygenase 1(HO-1)proteins in superior mesenteric artery tissue of the rats in various groups;the pathomorphology of the superior mesenteric artery of the rats in various groups was observed.Results:All the rats in normal group survived for 72 h,while the longest ST of the rats in model group did not exceed 9 h.Compared with model group,the ST and 24 h survival rate(SR)of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the BP,HR,and RR of the rats in model group were significantly decreased(P＜0.01).Compared with model group,the BP,HR,and RR of the rats in treatment group were significantly increased after fluid resuscitation(P＜0.05).Compared with normal group,the activities of AST and ALT,and the levels of Scr and BUN in serum of the rats in model group were significantly increased(P＜0.01).Compared with model group,the serum levels of LAC and GLU of the rats in treatment group were significantly decreased(P＜0.01).Compared with normal group,the concentration of iron ion,GSH level,MDA level,LDH activity in serum of the rats in model group were significantly increased(P＜0.05);compared with model group,the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased(P＜0.01).Compared with normal group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased(P＜0.05);compared with model group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased(P＜0.01);compared with model group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased(P＜0.01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered,the swelling was significant and the thickness was increased;the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated.The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact,and there was no swelling in the subendothelial matrix;the vascular endothelial cell membrane of the rats in model group was damaged,there were cytoplasmic dissolution and fragmentation,and the swelling of the subendothelial matrix was significant;the swelling of the vascular endothelial cells in treatment group was alleviated.Conclusion:Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock,and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Objective:To analyze the hotspots and trends of the researches on artificial intelligence (AI) in the diagnosis and treatment of traumatic brain injury (TBI).Methods:Based on the core database of Web of Science, the studies over AI in the diagnosis and treatment of TBI published from January 2000 to June 2024 were obtained by searching with the subject headings. VOSviewer software was used to analyze the publication year trend, country publication volume, country cooperation network, author publication volume, author citation frequency and author cooperation network. CiteSpace software was also used to identify key words with a significant rise in frequency over a short period of time to obtain the research trends.Results:A total of 2 662 relevant studies were retrieved, from which 677 related with AI in the diagnosis and treatment of TBI were finally enrolled. The number of published studies per year generally showed a rapid growth from 2018 to 2023. The United States had the highest number of publications as a country (362 studies). The author Camarillo had the most publications (9 studies). Rehabilitation was the keyword with the highest frequency (133 times) and the clustering topics containing the three largest number of keywords were virtual reality (VR), mild TBI, and deep learning. The keywords of mobile application, mobile health and intracranial pressure showed a significant increase in frequency from January 2022 to June 2024.Conclusions:VR technology, mild TBI and deep learning technology are the research hotspots of AI in TBI diagnosis and treatment. Mobile apps, mobile health, and intracranial pressure may be new research trends for AI in the diagnosis and treatment of TBI.

A female patient, years of age 56, having no distinct inducement before 5 d but developed fever, coughing, and shortness of breath, presented in People′s Hospital of Zhongshan with community-acquired pneumonia on March 3rd, 2023. Influenza A virus infection was confirmed on March 11th after performing macro transcriptome sequencing with alveolar lavage fluid, and H3N8 was confirmed with influenza typing afterward, having declared dead on March 16th. This case is a patient with refractory multiple myeloma autologous stem cell transplantation and continuous chemotherapy with immune dysfunction. She has a history of chronic upper respiratory tract infection. Imaging showed a widespread distribution of plaques, solid lesions, and other pneumonia manifestations in both lungs, a severe decrease in the counts of white blood cells, platelets, neutrophils, and lymphocytes, and a significant increase in laboratory inflammation indicators. After the clinical consideration was an acute aggravation of chronic respiratory tract infection and poor effect of anti-bacterial treatment, fungal infection was considered, and antibiotic treatment was changed several times according to the condition. Still, the outcome was poor, and the disease progressed rapidly. Medical workers initiated Oseltamivir antiviral therapy immediately after the alveolar lavage fluid etiology confirmed A-H3N8 influenza. However, due to complex and varied systemic symptoms, including inflammatory storm, sepsis, acute respiratory failure, tachycardia, coagulopathy, and other extrapulmonary organ injuries, she died 19 days after signs due to severe respiratory failure and multiple organ failure.

In the treatment of Hodgkin lymphoma (HL), it is important to avoid delayed side effects while improving efficacy, the immunotherapy provides an excellent option. The programmed death receptor 1 (PD-1) inhibitors are effective drugs for the treatment of relapsed/refractory HL. Meanwhile, the high effectiveness and tolerance of PD-1 inhibitors also provide the possibility for combination therapy. This article reviews the research progress of PD-1 inhibitors in the treatment of relapsed/refractory HL.

Helicobacter pylori (Hp) infection is closely related to the occurrence and development of chronic gastritis, peptic ulcer, and gastric cancer. At present, the treatment of Hp is mainly the bismuth-containing quadruple therapy as the first-line treatment to eradicate Hp infection. However, the eradication treatment still faces the challenges related to the rising antibiotic resistance, the decrease in eradication rate year by year, the adverse events, the poor patient's compliance and the dysregulation of gastrointestinal microbiome. Therefore, more and more researches are focusing on finding an effective treatment with the use of natural therapy. This article reviewed the research progress of pathogenic mechanism and treatment of Hp infection.

Objective:To evaluate the efficacy and safety of modified FC/ATG pretreatment in the treatment of severe aplastic anemia(SAA).Methods:From June 2012 to June 2020, clinical data of 64 patients with severe aplastic anemia undergoing allogeneic hematopoietic stem cell transplantation with modified FC/ATG(Flu 30 mg·m -2·d -l, -5~-2 d、CTX 50 mg·kg -1·d -1~-2 d、ATG: 2.5 mg·kg -1·d -1, -5~-2 d) pretreatment were retrospectively analyzed.There were MSD-HSCT ( n=29) and Haplo-HSCT ( n=35). Results:One patient died of intracerebral hemorrhage before transplantation and the remainders were completely implanted.During a median follow-up period of 14.5(1-95) months, overall survival (OS) rate of 92.2%.It was significantly higher than OS rate of 67.2% in the treatment of SAA by foreign pretreatment regimens containing low-dose TBI.And pretreatment scheme containing FC+ BU/TBI had an OS of slightly >91.3% in the treatment of SAA.The 3-year OS rates were 85.7% and 93.5% in Haplo-HSCT and MSD-HSCT groups ( P=0.058). The OS rate of SAA Haplo-HSCT/MSD-HSCT group was similar to that of " Beijing Protocol" (BU/CY+ ATG) (89%, 91%). The viral infection rates of EB and CMV were significantly higher in haplo-HSCT group than those in MSD-HSCT group and inter-group difference was statistically significant ( P<0.05). However, univariate analysis showed that two groups had no effect on survival time ( P=0.403, P=0.132). Univariate analysis showed that survival time was significantly associated with the presence of Ⅲ-Ⅳ° aGVHD and the presence of severe complications ( P=0.007, P=0.001). Further multivariate analysis revealed that severe complication was an independent risk factor for survival ( P=0.003). Conclusions:The efficacy of improved FC/ATG pretreatment in the treatment of SAA in MSD-HSCT or Haplo-HSCT is higher than other domestic and international pretreatment schemes in OS rate, safety and effectiveness.Onset of severe complication and association with Ⅲ ~ Ⅳ ° aGVHD are the influencing factors for patient survival.The efficacy of Haplo-HSCT group is similar to that of MSD-HSCT group.It may be employed as an alternative donor for SAA patients without fully congruent donors.

Objective:To compare the effects of two pretreatment schemes on the efficacy, gonad and reproductive function of haploid hematopoietic stem cell transplantation recipients with severe aplastic anemia(SAA).Methods:The data of 73 patients with SAA who underwent haploid hematopoietic stem cell transplantation were analyzed retrospectively.The pretreatment scheme was divided into Fludarabine+ Cyclophosphamide+ Antithymocyte globulin group(FC lowATG group, 45 cases)and Busulfan+ Cyclophosphamide+ Antithymocyte globulin group(Bucy/ATG group, 28 cases). The changes of blood cell implantation time, follicle stimulating hormone(FSH), luteinizing hormone (LH), estradiol and testosterone were compared between the two groups. Results:there was no significant difference in blood cell implantation time between the two groups( P=0.096; P=0.133). The levels of FSH and LH in female recipients in Bucy/ATG group were higher than those in FC lowATG group, and the level of estradiol was lower than that in FC lowATG group.There were significant differences between the groups(all P<0.05). The pregnancy or fertility rate of female recipients in Bucy/ATG group was lower than that in FC lowATG group(all P<0.05). There was no significant difference in FSH, LH, testosterone and fertility between the two groups(all P>0.05). There was no significant difference in 2-year overall survival rate and failure free survival rate between the two groups( P=0.091; P=0.084). Conclusions:FC lowATG may be an effective pretreatment scheme for haploid hematopoietic stem cell transplantation in SAA with less damage to gonad and reproductive function.

Objective:To investigate the effects of histone deacetylase inhibitor Chidamide (CS055) and DNA methyltransferase inhibitor decitabine (DAC) on proliferation and apoptosis of acute myeloid leukemia cell line U937 and its possible mechanism.Methods:U937 cells were cultured in vitro and treated with CS055 (CS055 single drug group), DAC (DAC single drug group), combination (combined drug group)and a negative control group. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the proliferation inhibition rate. The apoptosis rate was detected by flow cytometry.The mRNA expression of DNA methyltransferase 1 (DNMT1) was analyzed by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Western blot was used to analyze the expression of acetylated histone H3 and DNMT1. Results:The proliferation inhibition rate of U937 cells treated with CS055 and DAC increased significantly in a time-dose-dependent manner. The inhibitory effect of the combination group was more obvious than that of the single drug group. Flow cytometry showed that the 72 h apoptotic rates in the control group, 0.25 μ mol/L CS055 group and 2.5 μ mol/L DAC group were (0.67±0.12)%, (23.43±0.50)%, (8.47±0.32)%, (32.73±0.42)%. The apoptotic rate was significantly increased in the combination group compared with the single drug group. qRT-PCR showed that the expression of DNMT1 mRNA was down-regulated after CS055 and DAC treat alone; the down-regulating effect of the combination group was more significant. Western blot showed that the up-regulation of Ac-H3 and the decrease of DNMT1 in the combination group were significantly higher than those in the single drug group.Conclusions:The application of CS055 and DAC alone could inhibit the proliferation and induce apoptosis of U937 cells. The combination of the two drugs has obvious synergistic effect. The mechanism is that histone deacetylase inhibitors have demethylation effects, and demethylation drugs also have the effect of histone deacetylase inhibitors, which in combination increases demethylation and increases histone deacetylation.

Objective To study the suppressive mechanism of the bromo structural domain inhibitor JQ1 on the acute myeloid leukemia cell line U937 and its regulation of the STAT-5 signaling pathway. Methods U937 cells in the logarithmic growth phase were tested. Each experimental group was fed with 0.2, 1.0 and 4.0μmol/L of JQ1, and a blank control group without JQ1 was set up. U937 cells were cultured for 48 h, and the cell proliferation inhibitory rate was measured by MTT assay. Flow cytometry (FCM) was used to detect the apoptotic rate. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of focal adhesion kinase (FAK) and P21 activated kinase (PAK1). The expression of STAT-5 protein was analyzed by Western blot. Results Different concentration of JQ1 could inhibit the proliferation of U937 cells in a time and dose-dependent manner, and different concentration of JQ1 could induce the apoptosis of U937 cells in a dose-dependent manner. Treatment of U937 cells with different concentrations of JQ1 (0.2, 1.0 and 4.0 μmol/L) reduced the expression of FKA mRNA and PAK1 mRNA after 48 h, the expression of FAK mRNA was 0.417±0.066, 0.140±0.026, and 0.027±0.006 (F=454.651, P=0.000), and the expression of PAK1 mRNA was 0.533±0.045, 0.080±0.010, and 0.010±0.001 (F=2434.610, P= 0.000), and STAT-5 protein expression was also significantly inhibited. The expression of STAT-5 protein in U937 cells after treated with different concentrations of JQ1 (0.2, 1.0 and 4.0 μmol/L) for 48 h were 0.71± 0.19, 0.62±0.16, 0.53±0.14, and 1.00±0.21 in the control group (F= 263.135, P= 0.000). Conclusion JQ1 can effectively inhibit the proliferation of the acute myeloid leukemia cell line U937 cells and induce their apoptosis, and the possible mechanism of action is regulated via STAT-5 signaling pathway.