Neumannanker6969

Likewise, in the HOS cell line, afatinib decreased phosphorylation of key components in the ErbB signaling pathway. CONCLUSIONS Afatinib shows relevant antitumor effect in several osteosarcoma cell lines, as it causes a significant impact on cell viability, motility, and migration with a significant decrease in the activation of ErbB pathway activity.PURPOSE Multiple lung lesions found in a single patient at the time of diagnosis often pose a diagnostic dilemma are these lesions independent primary tumors (IPT) or the result of intrapulmonary metastases (IPM)? While traditional pathological methods sometimes have difficulty distinguishing IPM from IPT, modern molecular profiling based on next-generation sequencing techniques may provide a new strategy. METHODS Sixteen patients with multiple tumors were enrolled in this study. We performed targeted deep sequencing (~ 2000 × coverage) on a total of 40 tumors and matched blood samples. We compared mutational profiles between tumors within each patient and across patients to evaluate if they were genetically related. Computed tomographic images and histological staining were also used to validate tumor relationships. RESULTS A total of 125 mutations were identified in 16 patients. Twelve out of fourteen patients whose histological diagnoses favored IPT did not have any shared mutations in their multiple tumors. The other two showed discrepancies Pt01 had a shared EGFR exon19 deletion in the two lung tumors found, and Pt16 had one common mutation (BRAFD594G) in two out of five lung tumors. Pt14 with lung metastasis from salivary gland adenoid cystic carcinoma had shared mutations; and Pt15 with suspected intrapulmonary metastasis (IPM) had identical mutations between the two tumors. Visualized data can be readily accessed through the website mlc.opengene.org. CONCLUSION Analysis of overlapping mutations among different tumors assists physicians in distinguishing IPM from IPT. Our findings demonstrate that DNA sequencing can provide additional evidence in clinical practice when pathology is inadequate to make a conclusive diagnosis.Within the evidence-based medicine (EBM) construct, clinical expertise is acknowledged to be both derived from primary experience and necessary for optimal medical practice. Primary experience in medical practice, however, remains undervalued. Clinicians' primary experience tends to be dismissed by EBM as unsystematic or anecdotal, a source of bias rather than knowledge, never serving as the "best" evidence to support a clinical decision. The position that clinical expertise is necessary but that primary experience is untrustworthy in clinical decision-making is epistemically incoherent. Here we argue for the value and utility of knowledge gained from primary experience for the practice of medicine. Primary experience provides knowledge necessary to diagnose, treat, and assess response in individual patients. Hierarchies of evidence, when advanced as guides for clinical decisions, mistake the relationship between propositional and experiential knowledge. We argue that primary experience represents a kind of medical knowledge distinct from the propositional knowledge produced by clinical research, both of which are crucial to determining the best diagnosis and course of action for particular patients.PURPOSE Nasal polyp formation is a common sequela of prolonged chronic rhinosinusitis, but the mechanism underlying this disease state is still controversial. We compared the expressions of Cl- channels/transporters in nasal polyps with those in inferior turbinates to explore whether a deficiency in Cl- transport may participate in the pathophysiology of nasal polyp formation as in patients with cystic fibrosis. METHODS Nasal polyps and inferior turbinates were collected from 12 chronic rhinosinusitis patients with hypertrophic rhinitis and/or nasal polyps. Expressions of cystic fibrosis transmembrane conductance regulator (CFTR), pendrin, Na+-K+-2Cl- cotransporter 1 (NKCC1), SLC26A3, TMEM16A and anion exchanger 2 (AE2) were examined by fluorescence immunohistochemistry using Alexa Fluor 488. RESULTS CFTR was weakly expressed on the epithelial surface of the turbinate mucosa whereas the nasal polyps showed almost no fluorescence. Pendrin was mainly expressed on the epithelial surface in both tissues. The fluorescence was moderate in the nasal polyps and strong in the turbinate mucosa. For NKCC1, moderate fluorescence was observed throughout the entire epithelial layer of the nasal polyps, but the turbinate mucosa exhibited almost no fluorescence. On the other hand, no fluorescence for SLC26A3, TMEM16A or AE2 was seen in either tissue. CONCLUSION These results suggest that CFTR, pendrin and NKCC1 may participate in the pathogenesis of nasal mucosal edema and play roles in the mechanism of nasal polyp formation.PURPOSE Oropharyngeal cancer (OPC) remains a significant health burden and about 15-30% of these have been attributed to the human papillomavirus (HPV). Human papillomavirus-related oropharyngeal cancer (HPV OPC) includes tumours which are detected to be p16INK4A positive or have the HPV DNA detected by in situ hybridisation or polymerase chain reaction. HPV OPC is generally believed to have a relatively good prognosis. More recently, there is a recognised pattern of atypical spread in a highly aggressive subset of HPV OPC. These are HPV OPCs which develop distant metastasis or recurrence. This review raises awareness of this subset of HPV OPC and factors associated with poor outcomes. METHODS A review of the literature available on HPV OPC was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. RESULTS Factors associated with highly aggressive HPV OPC include nodal stage and nodal morphology, alcohol and tobacco use, age and biological characteristics. Treatment options in cases of disease recurrence include salvage resection radiotherapy and/or chemotherapy and management options vary depending on the nature of recurrence and initial treatment. Recent updates in HPV OPC staging have made staging and treatment of tumours more accurate. CONCLUSION While HPV OPC overall carries a relatively good prognosis, it is important for clinicians to be aware of potentially highly aggressive cases of HPV OPC and to be aware of factors that should prompt close monitoring.OBJECTIVES To explore the rule of extended high-frequency (EHF) audiometry recovery in patients with acute otitis media. METHODS From January 2016 to July 2019, patients with acute otitis media in the outpatient department of otology were studied. The diagnosis was made according to the otoscopy and acoustic impedance tests, and antibiotics and other treatment programs were given. The patients were followed up to compare the effects of different recovery time on extended high-frequency audiometry in patients with acute otitis media. RESULTS 146 patients with acute otitis media (69 in the left ear and 77 in the right ear) were selected for observation and follow-up. The patients were divided into three groups according to the time from the onset to the disappearance of hyperacusis and earache symptoms ≤ 5 days group (26 patients, 17.8%), 6-10 days group (74 patients, 50.7%), and > 10 days group (46 patients, 31.5%). The threshold of EHF in the study group was significantly higher than that in the control group in the early stage. According to the study design for follow-up, we found that with the prolongation of the duration of acute otitis media, the extended high frequency of different groups had different changes. CONCLUSIONS Our results show that the recovery time of EHF in patients with acute otitis media was later than that of the standard audiogram and was closely related to the course of the disease. This is of great significance for discovering the hidden hearing loss of the patients and taking the treatment plan as soon as possible.BACKGROUND An initial study enabled us to achieve 60% healing of high transsphincteric fistula-in-ano with laser ablation of fistula tract (LAFT) The purpose of this new study was to investigate other predictors of the success of this technique in the treatment of complex anoperineal fistulas. METHODS All patients treated with LAFT in our department between May 2017 and October 2018 were included prospectively. LAFT was used for patients with complex anoperineal fistulas who were at high risk of anal incontinence after fistulotomy. The fistula was considered healed when the internal and external openings were closed and the patient experienced no pain or leakage. RESULTS A total of 100 consecutive patients (65 males) with a median age of 43 years (range 22-88 years) were included in the study. Eight patients were lost to follow-up. The fistulas were low (8%) or high (79%) transsphincteric, and suprasphincteric (13%). After a median follow-up of 13.6 months (range 6-23 months), fistula healing was observed in 41 patients (44.6%). On univariate analysis, an anterior location, a narrow internal orifice and administration of less than 400 J of energy were significantly associated with healing. On multivariate analysis, a narrow internal orifice and low energy administration remained significant predictive factors of success [OR 5.08 (1.03-25.03), p = 0.046; OR 2.59 (1.08-6.17), p = 0.032]. No new cases of anal incontinence or any worsening of pre-existing anal incontinence was observed during follow up. CONCLUSIONS This study indicates that complex anoperineal fistulas with a narrow internal orifice can be successfully treated with less than 400 J and are ideal for LAFT.RATIONALE Since the precise mechanisms of posttraumatic stress disorder (PTSD) remain unknown, effective treatment interventions have not yet been established. Numerous clinical studies have led to the hypothesis that elevated glucocorticoid levels in response to extreme stress might trigger a pathophysiological cascade which consequently leads to functional and morphological changes in the hippocampus. OBJECTIVES To elucidate the pathophysiology of PTSD, we examined the alteration of hippocampal gene expression through the glucocorticoid receptor (GR) in the single prolonged stress (SPS) paradigm, a rat model of PTSD. METHODS We measured nuclear GRs by western blot, and the binding of GR to the promoter of Bcl-2 and Bax genes by chromatin immunoprecipitation-qPCR as well as the expression of these 2 genes by RT-PCR in the hippocampus of SPS rats. In addition, we examined the preventive effects of a GR antagonist on SPS-induced molecular, morphological, and behavioral alterations (hippocampal gene expression of Bcl-2 and Bax, hippocampal apoptosis using TUNEL staining, impaired fear memory extinction (FME) using the contextual fear conditioning paradigm). RESULTS Exposure to SPS increased nuclear GR expression and GR binding to Bcl-2 gene, and decreased Bcl-2 mRNA expression. Administration of GR antagonist immediately after SPS prevented activation of the glucocorticoid cascade, hippocampal apoptosis, and impairment FME in SPS rats. CONCLUSION The activation of GRs in response to severe stress may trigger the pathophysiological cascade leading to impaired FME and hippocampal apoptosis. In contrast, administration of GR antagonist could be useful for preventing the development of PTSD.