Retrograde nerve growth factor signaling modulates tooth mechanical hyperalgesia induced by orthodontic toothmovement via acid-sensing ion channel 3

INTRODUCTION Orofacial pain, with a prevalence of 16％ among general population,1 is a constellation of painful conditions in the orofacial regions and comprises...     

Combined application of MRS and DWI can effectively predict cell proliferation and assess the grade of glioma: A prospective study

In order to assess combined application of MRS and DWI for prediction cell proliferation and grade diagnosis of glioma, We prospectively collected the Cho/Cr, Cho/NAA, Cr/NAA of MRS and tumor parenchyma ADC (ADC_T), contralateral mirror brain tissue ADC (ADC_H), rADC (rADC = ADC_T/ADC_H). According to postoperative pathology, the patients were divided into two groups: LGG group and HGG group, compared differences of age, gender, Ki67, MRS, DWI between two groups. Next, we analyzed the correlation between MRS, DWI and Ki67. On this basis, the sensitivity and specificity of MRS, DWI and MRS combined with DWI (MRS + DWI) in diagnosis of glioma grade were evaluated. The differences of Ki67, Cho/Cr, Cho/NAA, Cr/NAA, ADC_T, rADC between LGG group and HGG group were statistically significant (p = 0.000, 0.000, 0.000, 0.008, 0.000, and 0.000 respectively). From ROC curve, area under the curve (AUC), sensitivity and specificity of Cho/Cr, Cho/NAA, Cr/NAA, ADC_T, rADC, PRE (MRS + DWI) were (0.901, 86.7%, 85.7%), (0.876, 80.0%, 82.1%), (0.704, 63.3%, 71.4%), (0.862, 82.1%, 83.3%), (0.820, 75.0%, 76.7%), (0.920, 86.7%, 89.3%), respectively. Fisher's linear discriminant functions results suggest: Y₁ = -20.447 + 3.46•X₁ + 17.141•X₂ (LGG), Y₂ = -19.415 + 4.828•X₁ + 14.543•X₂ (HGG). Our study suggested that MRS and DWI can effectively predict cell proliferation preoperative. MRS combined with DWI can further improve sensitivity and specificity in assessing the grade of glioma.     

ABO blood groups do not predict progression of traumatic intracranial hemorrhage

ABO blood groups are associated with genetically predisposed variations in von Willebrand factor (VWF) resulting in higher risks of thrombotic events in non-O blood types and bleeding complications in blood type O. The role of ABO blood groups in progression of traumatic intracranial hemorrhage (TICH) is unknown. Given statistically lower VWF levels in blood type O in the general population, we hypothesized that blood type O patients have a higher risk of such progression. A retrospective review of adult trauma patients with isolated TICH admitted to a Level 1 trauma center over eight years was conducted. Patients were categorized with blood type O and non-O (types A, B, AB) delineation. The primary outcome was radiological progression of TICH during the first 24 h. Secondary outcomes included surgical intervention after follow-up computed tomography (CT), complications, days on mechanical ventilation (DMV), intensive care unit (ICU) length of stay (LOS), hospital LOS, and mortality. Of 949 patients, 432 (45.5%) had blood type O. When comparing O and non-O groups, no significant differences were found in gender, age, race, admission vital signs, Glasgow Coma Scale, coagulation profile, TICH type, or Injury Severity Score. No difference in TICH progression was found between O and non-O groups: 73 (17%) vs 80 (15%), respectively, p = 0.55. Blood type O mortality was 12 (3% vs. 23 (4%), p = 0.174). Rate of TICH surgical intervention after follow-up CT, DMV, complications, and ICU and hospital LOS did not differ. No association between ABO blood types and radiological progression of TICH was identified.     

The immunologic dominance of an epitope within a rationally designed poly-epitope vaccine is influenced by multiple factors

IntroductionCD4⁺ T cells are essential for inducing optimal CD8⁺ T cell and antibody-producing B cell responses and maintaining their long-term immunological memory. Therefore, CD4⁺ T cells are a critical component in HIV vaccine development. Due to enormous viral gene variation and significant human host genetic diversity, HIV vaccines may need to be custom-made for different countries.MethodsPreviously, we designed a CD4⁺ T cell vaccine based on Chinese HIV isolates and HLA-DR alleles using bioinformatics tools and predicted that 20 epitopes could cover 98.1% of the Chinese population. In vivo testing of the poly-epitope antigen in mice only activated specific T cells for some epitopes. To elucidate the mechanism of the observed differential immunogenicity, we examined poly-epitope antigen processing and presentation using in vitro and in vivo analytical methods.ResultsEnzymatic digestion indicated that all 20 epitopes comprising the poly-epitope antigen could be liberated, but MHC II binding assays showed that neither binding affinity nor dissociation rate was associated with the magnitude of T cell immune responses elicited by each peptide epitope in vaccinated mice. Mass spectrometry analysis of MHC II-bound peptides suggested that the abundance of endogenously processed peptides bound to MHC II molecules was significantly associated with the relative immunodominance of these epitopes.ConclusionThese results provide a new rationale for improving the design and testing of poly-epitope vaccines for HIV and other diseases.     

LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression

Large tumor suppressor 2 (LATS2) plays significant roles in tumorigenesis and cancer progression. This study was aimed to analyze the correlation between LATS2 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). LATS2 expression was examined in 73 NSCLC clinical specimens and 22 normal lung tissues using immunohistochemistry. Low levels of LATS2 protein were inversely associated with the T classification (P = 0.001), N classification (P = 0.005) and clinical stage (P = 0.001) in NSCLC patients. Patients with lower LATS2 expression had a significantly shorter overall survival than patients with high LATS2 expression. Multivariate analysis suggested that low expression of LATS2 was an independent prognostic indicator (P = 0.002) for the survival of patients with NSCLC. Furthermore, overexpression of LATS2 resulted in mobility inhibition in NSCLC cell lines A549 and H1299, and reduced protein level of matrix metalloproteinase-2 (MMP-2) and MMP-9. On the contrary, LATS2 siRNA treatment enhanced cell mobility and increased MMP-2 and MMP-9 protein expression level. In conclusion, low expression of LATS2 is a potential unfavorable prognostic factor and promoted cell invasion and migration in NSCLC.