Objective To explore the neurasthenia situation of the population attending the postgraduate exam in medical class and its influencing factors .Methods The random cluster sampling method was adopted .The influencing factors were per‐formed the χ2 test and Logistic regression analysis .Results According to the inclusion criteria and exclusion criteria ,36 positive ca‐ses were screened out ,accounting for 8 .89% of participants ,which was higher than the value of the general population ;the statisti‐cally significant differences were noted in the factors of the confidence of attending the postgraduate exam ,stress ,adjusting ability , interpersonal situation ,reading duration ,sleep ,nutrition and dietary (P<0 .05) .Conclusion Attending the postgraduate exam such highly intensitive mental activity is the important reason causing neurasthenia among the population attending the postgraduate ex‐am ,which mainly display in the aspects of stress size ,bearing ability facing stress and regulation .

Objective To investigate the effect of intrathecal nerve growth factor (NGF) on lidocaineinduced neurotoxicity to the spinal cord in rats.Methods Thirty healthy male Sprague-Dawley rats,aged 8-10 weeks,weighing 250-300 g,were randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),sham operation group (group S),lidocaine-induced neurotoxicity group (group L),normal saline group (group NS) and NGF group (group NGF).A catheter was inserted at L4.5 interspace into the epidural space in S,L,NS,and NGF groups.One day after surgery,20％ lidocaine 20 μl was injected intrathecally.At 24 h after lidocaine injection,normal saline 20 μl and NGF 10 μg (20 μd) were injected intrathecally in NS and NGF groups,respectively,once a day for 7 consecutive days.The tail flick latency (TFL) to a thermal nociceptive stimulus was measured on 1,3,5 and 7 days after lidocaine injection.The animals were sacrificed after the behavioral test was completed at 7 days after lidocaine injection,and the lumbar segments of the spinal cord were removed to detect the neuronal apoptosis (using flow cytometry) and caspase-3 mRNA expression (by RT-PCR).Results Compared with group C,the TFL was significantly prolonged at 1-7 days after lidocaine injection in L and NS groups and at 1-5 days after lidocaine injection in group NGF,the apoptosis rate was increased in L,NS and NGF groups,and caspase-3 mRNA expression was up-regulated in L and NS groups,and no significant change was found in the parameters mentioned above in group S.Compared with group L,the TFL was significantly shortened at 5 and 7 days after lidocaine injection,the apoptosis rate was decreased,and caspase3 mRNA expression was down-regulated in NGF group,and no significant change was found in the parameters mentioned above in group NS.Conclusion Intrathecal NGF can reduce lidocaine-induced neurotoxicity to the spinal cord in rats and inhibition of caspase-3 mRNA expression is involved in the mechanism.

Objective To analyze and summarize the risk factors of failed internal fixation for intertrochanteric fracture.Methods From April 2008 to April 2011,267 patients with intertrochanteric fractures in 4 hospitals were treated with internal fixation.The relationship between the failure of internal failure and possible factors as age,gender,hypertension,diabetes,the abuse of alcohol and tobacco,use of glucocorticoid,the degree of osteoporosis and fractures type were studied.According to the surgical risk assessment table,the patients were divided into low-risk,mid-risk,and high-risk group.The rate of internal fixation failure was compared in the 3 groups.Results We found 42 cases which showed radiographic failures.The internal fixation failure directly related with advanced age,diabetes,severe osteoporosis,unstable type fracture,but not gender,hypertension,the abuse of alcohol and tobacco,use of glucocorticoid.Risk factors of internal fixation failure included diabetes,osteoporosis degree,and fracture stability.Failed intertrochanteric fracture fixation mainly occurred in the mid-risk and high-risk groups.Conclusion Severe osteoporosis,unstable fracture,diabetes are risk factors of failure of intertrochanteric fracture fixation.These factors will affect the quality of surgery.For the patient with intertrochanteric fractures in the low-risk groups,internal fixation should be the first choice for treatment.For the patients in the mid-risk and high-risk group,internal fixation should be applied cautiously.For the aged patients in high-risk groups,hip arthroplasty is a wise option.

PURPOSE: To investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer’s disease (AD) rat model. MATERIALS AND METHODS: Rats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)₁₋₄₀ was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ₁₋₄₀ injection. Learning and memory capabilities were examined using the Morris water maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin-eosin staining and immunohistochemistry, respectively. Dendritic spine density was determined by Golgi-Cox staining. Tumor necrosis factor-α, interleukin-1β, and interleukin-10 production was assessed by enzyme-linked immunosorbent assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Protein expression was examined by western blotting. RESULTS: Learning and memory dysfunction was ameliorated in the HBO+AD group, as shown by significantly lower swimming distances and escape latency, compared to the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed in the HBO+AD than in the AD group. CONCLUSION: HBO pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD rats.
Alzheimer Disease/*therapy ; Amyloid beta-Peptides/*administration & dosage ; Animals ; Apoptosis ; *Cognition/drug effects ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Hippocampus/*enzymology ; *Hyperbaric Oxygenation ; In Situ Nick-End Labeling ; Interleukin-10/biosynthesis ; Interleukin-1beta/biosynthesis ; Learning/drug effects ; Male ; Memory/drug effects ; Neurons ; Peptide Fragments/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/administration & dosage ; Tumor Necrosis Factor-alpha/biosynthesis ; p38 Mitogen-Activated Protein Kinases/*metabolism

Objective:To investigate the impact of the deep learning reconstruction algorithm TrueFidelity TM for Gemstone Spectral Imaging (TF-GSI) and the adaptive statistical iterative reconstruction algorithm (ASiR-V, hereinafter referred to as ASiR-V) based on phantom and animal models on the image quality of dual-energy CT images. Methods:GE Revolution Apex CT was used to scan the ACR 464 phantom and a mouse model of gastric cancer with lymph node metastasis ( n=16). TF-GSI and ASiR-V were separately used to reconstruct middle and high-grade images (TF-GSI-M, TF-GSI-H, ASiR-V-50%, and ASiR-V-100%) on the phantom and mouse based on virtual monoenergetic images at 70 keV. The task transfer function (TTF) of bone and acrylic, image noise power spectrum (NPS), and detectability index (d′) of the phantom images were evaluated. One-way ANOVA analysis was used to compare the image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for brain and liver on images of mice. The consistency of the two reconstruction-algorithm images (TF-GSI-H and ASiR-V100%) in the detection of small lesions by two radiologists (A and B) was evaluated using kappa test. Results:In terms of the phantom, the TF-GSI-H group had the best performance in TTF, NPS, and d′. Compared to ASiR-V-100%, the TTF50% of bone and acrylic in the TF-GSI-H group increased by 2.4% and 8.9%, respectively; the NPS peak decreased by 54.1%, compared to ASiR-V-100%; the d′ of bone and acrylic in the TF-GSI-H group relative to ASiR-V-100% increased by 52.7% and 59.5%, respectively. The TF-GSI group had reduced image noise compared to the ASiR-V group, and both SNR and CNR of the two tissues increased, but the differences between the groups were not statistically significant (all P>0.05). The two reconstruction-algorithm images showed good consistency in image evaluation by the two radiologists (A, Kappa=0.875, P<0.001; B, Kappa=0.625, P=0.012). In terms of the detection of micro-metastases in mice, the TF-GSI group outperformed the ASiR-V group (average accuracy: 83.5% vs 71.9%; average sensitivity: 77.8% vs 61.2%; average specificity: 85.7% vs 85.7%). Conclusion:Compared with iterative reconstruction algorithm, the DLIR algorithm showed improved spatial resolution, reduced image noise, and enabled detectability of micro-lesion for images from dual-energy CT.

BACKGROUND: Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma. METHODS: The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry. RESULTS: Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion. CONCLUSIONS This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.
Humans ; Animals ; Mice ; Carcinoma, Hepatocellular/radiotherapy* ; Cell Cycle Proteins/metabolism* ; Protein-Tyrosine Kinases/genetics* ; Apoptosis ; Programmed Cell Death 1 Receptor ; Cell Line, Tumor ; G2 Phase Cell Cycle Checkpoints ; Liver Neoplasms/radiotherapy* ; Tumor Microenvironment ; Pyrazoles ; Pyrimidinones

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.
Cytoskeletal Proteins ; Endothelial Cells ; Extracellular Traps ; Integrins ; Intercellular Adhesion Molecule-1 ; Lipopolysaccharides/pharmacology* ; Macrophages ; Neutrophils

Extracellular traps released by neutrophils (neutrophil extracellular traps, NETs) are a double-edged sword, and understanding the mechanism of NET formation is of great significance for disease treatment. However, the short lifespan, the large individual differences, and the inability to perform gene editing render it difficult to decipher NET formation using neutrophils. It is necessary to find a model cell to replace neutrophils to study the mechanism of NET formation. In this study, we used different concentrations (0, 0.1, 1, and 10 μmol/L) of all-trans retinoic acid (ATRA) to differentiate HL-60 cells for different days (1, 3, 5, and 7 days). By detecting the cell viability and nuclear morphology of cells, we confirmed that HL-60 cells were differentiated to neutrophil-like cells (dHL-60) after treated with ATRA for at least 5 days. Using immunofluorescence staining to detect the formation of NETs, we demonstrated that dHL-60 cells differentiated for 5 days with 1 μmol/L ATRA could generate NETs comparable to those produced by neutrophils upon phorbol 12-myristate 13-acetate (PMA) stimulation, without histone H3 citrullination. Furthermore, the formation of NETs by dHL-60 cells were NADPH-dependent and PAD4-independent, consistent with neutrophils. Taken together, these observations suggest that dHL-60 cells differentiated with 1 μmol/L ATRA for 5 days can be used as a model cell for neutrophils to study the mechanism of NET formation.
Humans ; Extracellular Traps ; Tetradecanoylphorbol Acetate/pharmacology* ; Neutrophils ; HL-60 Cells ; Tretinoin/pharmacology*