PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Intermittent hypoxia (IH) has preventive and therapeutic effects on hypertension, myocardial infarction, cerebral ischemia and depression, but its effect on post-traumatic stress disorder (PTSD) has not been known. In this study, we used inescapable electric foot shock combined with context recapture to build PTSD mouse model. The levels of fear and anxiety were valued by the open field, the elevated plus maze (EPM) and the fear conditioning tests; the level of spatial memory was valued by Y maze test; the number of Fos positive neurons in hippocampus, amygdala and medial prefrontal cortex was valued by immunohistochemical staining; and the protein expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) in these brain area were valued by Western blot. The results showed that IH and model (foot shock) had an interaction on percentage of entering open arms (OE%) in EPM and freezing time and the number of fecal pellets in fear conditioning test. IH increased OE% in EPM and reduced the freezing time and the number of fecal pellets in fear conditioning test in PTSD model mice. At the same time, IH reduced the number of Fos positive neurons in the hippocampus, amygdala and medial prefrontal cortex of PTSD model mice, and increased the protein expression levels of HIF-1α, VEGF and BDNF in these brain tissues. In conclusion, IH pretreatment can relieve fear and anxiety behavior in post-traumatic stress model mice, suggesting that IH may be an effective means of preventing PTSD.
Animals ; Anxiety ; therapy ; Brain-Derived Neurotrophic Factor ; metabolism ; Fear ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Mice ; Stress Disorders, Post-Traumatic ; therapy ; Vascular Endothelial Growth Factor A ; metabolism

Background: Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS. Methods: We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality. Results: Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ± 6.3 in the ECMO group and 24.8 ± 8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ± 3.4 in the ECMO group and 13.7 ± 3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001–1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264–8.609; P = 0.034). Conclusions This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.

Glutamate decarboxylase, a unique pyridoxal 5'-phosphate-dependent enzyme, catalyzes α-decarboxylation of L-glutamate to γ-aminobutyrate. However, glutamate decarboxylase from different sources has the common problem of poor thermostability that affects its application in industry. In this study, proline was introduced at 13 different positions in glutamate decarboxylase by using the design strategy of homologous sequence alignment between Thermococcus kodakarensis and Lactobacillus brevis CGMCC No.1306. A mutant enzyme G364P with higher thermostability was obtained. Compared to the wild type, thermostability of the mutant G364P was significantly improved, the half-life time (t1/2) at 55 °C and the semi-inactivation temperature (T₅₀ ¹⁵) of the mutant G364P increased 19.4 min and 5.3 °C, respectively, while kcat/Km of the mutant enzyme remained nearly unchanged. Further analysis of their thermostability by molecular dynamics simulations were performed. The root mean square deviation of G364P and root mean square fluctuation in the loop region including G364 were lower than the wild type at 313 K for 10 ns, and G364P increased one hydrophobic interaction in the loop region. It proves that mutation of flexible 364-Gly to rigid proline endows glutamate decarboxylase with enhanced thermostability.
Glutamate Decarboxylase ; Glutamic Acid ; Lactobacillus brevis ; Molecular Dynamics Simulation ; Proline

Objective This study aimed to explore the potential effects of terahertz (THz) waves on primary cultured neurons from 4 rat brain regions (hippocampus,cerebral cortex,cerebellum,and brainstem)and 3 kinds of neuron-like cells (MN9D,PC12,and HT22 cells) under nonthermal conditions.Methods THz waves with an output power of 50 (0.16 THz) and 10 (0.17 THz) mW with exposure times of 6 and 60 min were used in this study.Analysis of temperature change,neurite growth,cell membrane roughness,micromorphology,neurotransmitters and synaptic-related proteins (SYN and PSD95) was used to evaluate the potential effects.Results Temperature increase caused by the THz wave was negligible.THz waves induced significant neurotransmitter changes in primary hippocampal,cerebellar,and brainstem neurons and in MN9D and PC12 cells.THz wave downregulated SYN expression in primary hippocampal neurons and downregulated PSD95 expression in primary cortical neurons.Conclusion Different types of cells responded differently after THz wave exposure,and primary hippocampal and cortical neurons and MN9D cells were relatively sensitive to the THz waves.The biological effects were positively correlated with the exposure time of the THz waves.

Objective: To investigate the serum expression and influencing factors of hepcidinin patients with classical paroxysmal nocturnal hemoglobinuria (PNH) . Methods: Retrospective analysis of 36 classical PNH patients from 2016.3 to 2017.3. Serum hepcidin concentration was measured by ELISA method. The relationship between serum hepcidin concentration and erythropoiesis and iron homeostasis parameters was evaluated. Results: The median serum hepcidin level of 36 classical PNH patients was 32.03 (23.11, 118.48) μg/L, it was significantly lower than of 181.42 (106.80, 250.53) μg/L in 292 normal control subjects (z=-5.107, P<0.001) . The median serum hepcidin of 56.41 (44.60, 95.06) μg/L in PNH patients with normal ferritin was significantly lower than that in normal controls. The median serum hepcidin concentration 23.75 (21.77, 30.35) μg/L in iron deficiency PNH patients was lower than that in the normal ferritin PNH patients. However, the median serum hepcidin level of classical PNH with elevated ferritin patients 336.19 (304.19, 375.08) μg/L was significantly higher not only than that of normal ferritin and iron deficiency PNH ones, but also than that of normal control subjects. Regression analysis showed that serum ferritin, transferrin saturation and serum albumin level were independent influencing factors of serum hepcidin level in patients with classical PNH. Conclusion: The decreased serum hepcidin level in patients with classical PNH was mainly influenced by iron metabolism factors.
Enzyme-Linked Immunosorbent Assay ; Ferritins ; Hemoglobinuria, Paroxysmal ; Hepcidins ; Humans ; Retrospective Studies

OBJECTIVETo investigate the application and effect of minimally invasive percutaneous anterior pelvic pubic ramus screw fixation in Tile B fractures.

METHODSA retrospective review was conducted on 56 patients with posterior pelvic ring injury combined with fractures of anterior pubic and ischiadic ramus treated between May 2010 and August 2015, including 31 males and 25 females with an average age of 36.8 years old ranging from 35 to 65 years old. Based on the Tile classification, there were 13 cases of Tile B1 type, 28 cases of Tile B2 type and 15 cases of Tile B3 type. Among them, 26 patients were treated with sacroiliac screws combined with external fixation (external fixator group) and the other 30 patients underwent sacroiliac screw fixation combined with anterior screw fixation (pubic ramus screw group). Postoperative complications, postoperative ambulation time, fracture healing, blood loss, Majeed pelvic function score and visual analogue scale(VAS) were compared between two groups.

RESULTSFifty-four patients were followed up from 3 to 24 months with a mean of 12 months. There were no significant difference in the peri-operative bleeding and operation time between two groups(>0.05). The postoperative activity time and fracture healing time of pubic ramus screw group were shorter than those of the external fixator group, the differences were statistically significant(<0.05). The Majeed score, VAS score of pubic ramus screw group were higher than those of the external fixator group, the differences were statistically significant(<0.05). The incidence of postoperative complications of pubic ramus screw was lower than that of the external fixator group, the difference was statistically significant (<0.05).

CONCLUSIONSPercutaneous iliosacral screws fixation combined with the pubic ramus screw is an effective and safty treatment method to the Tile B pelvic fracture. It has advantages of early ambulation, relief of the pain and few complications.

BACKGROUND: Alloying can improve the corrosion resistance and slow the degradation of pure magnesium. In addition, increasing studies have shown that zinc has good antitumor effect. OBJECTIVE: To evaluate the effect of zinc-containing magnesium alloy on the proliferation and apoptosis of human osteosarcoma U2OS cells in vitro.METHODS: The corrosion resistance of pure magnesium and different zinc-containing (2%, 4%, 6%) magnesium alloys were observed and compared by the hydrogen release assay in the Hank's solution. MTT assay was used to examine the effects of different zinc-containing magnesium alloy extractions on the proliferation of U2OS cells (or MC3T3-E1 cells) after co-culture of 1, 3, 5 days. After 24-hour co-culture with pure magnesium, different zinc-containing magnesium alloys and titanium alloy extractions, the apoptotic rates of U2OS cells were analyzed by flow cytometry, and the expression of apoptosis-related proteins were detected by western blot assay.RESULTS AND CONCLUSION: The corrosion resistance of pure magnesium was improved after addition of Zn within the initial 100 hours, and the magnesium alloy containing 4% zinc exhibited the optimal corrosion resistance. Different zinc-containing magnesium alloy extractions obviously inhibited the U2OS proliferation in a zinc level-depended manner, and the cytotoxicity of different zinc-containing magnesium alloy extractions to MC3T3-E1 was graded 0-1. Different zinc-containing magnesium alloy extractions could also induce obvious apoptosis in U2OS cells in a zinc level-depended manner. Different zinc-containing magnesium alloy extractions, especially the magnesium alloy containing 4% zinc, up-regulated the expression of p53 and Bax proteins and down-regulated the expression of Bcl-2 protein in U2OS cells, leading to the disorder of Bcl-2/Bax. These findings suggest that different zinc-containing magnesium alloy extractions can inhibit the proliferation and induce apoptosis of U2OS cells in vitro.

Objective To evaluate the usefulness of diffusion-weighted imaging(DWI) in the diagnosis and differential diagnosis of gallbladder wall thickening diseases.Methods 42 patients with gallbladder wall thickening (16 patients with carcinoma and 26 patients with benign lesion) were included in this study.All patients performed conventional MRI and DWI.The diagnostic performances of three methods (conventional MRI,visual assessment of color fusion image from DWI and T2WI,and ADC measurement) were evaluated by two radiologists.Results The area under the receiver operating characteristic curve were 0.570,0.849,0.901 for conventional MRI,visual assessment and ADC measurement respectively.The accuracy,sensitivity and specificity were 59.5%,62.5%,57.7% for conventional MRI,85.7%,81.2%,88.5% for visual assessment of color fusion image,and 83.3%,80.0%,85.2% for ADC measurement,respectivily.The mean ADC value of gallbladder cacinoma[(1.15±0.35)×10-3mm2/s]was significantly less than that of gallbladder benign lesion [(1.99±0.61)×10-3mm2/s](P<0.01).Conclusion The DWI(visual assessment of color fusion image and ADC measurement)might be a useful tool for diagnosis and differential diagnosis of the gallbladder wall thickening diseases.