[Pay attention to the futile recanalization management of patients with acute ischemic stroke].

Vascular recanalization therapy has been proven to be one of the most effective treatments for acute ischemic stroke (AIS) worldwide. Recently, the neurological functions have dramatically improved for AIS patients receiving endovascular thrombectomy, especially after the issue and promotion of evidence from different clinical studies. But nearly 50% of the patients had unfavorable clinical outcome even after successful recanalization [modified thrombolysis in cerebral infarction (mTICI)≥2b/3], which was termed as"futile recanalization". The mechanisms are complex, which may be related to poor collateral circulation, microthrombus and small artery reocclusion. The most significant pathophysiological change is brain tissue hypoperfusion although complete opening of the large artery, known as"no-reflow phenomenon". Therefore, it is urgent to manage the complications after vascular recanalization, such as hemorrhagic transformation, hyperperfusion syndrome, vascular re-occlusion, and even surgery-related complications (arterial dissection, contrast-induced encephalopathy), and future research is warranted to focus on the strategy of drugs with multi-target protection combined with vascular recanalization treatment. The current article covers the review, original research and case report focusing on this topic, aiming to raise clinical questions and call for more contribution to explore the mechanism and potential therapeutic strategy of futile recanalization, and thus provides more selections on the improvement of clinical outcome for AIS patients.

Plasma metabolome alteration in dairy cows with left displaced abomasum before and after surgical correction.

Left displaced abomasum (LDA) leads to substantial changes in the metabolism of dairy cows. Surgical correction of LDA can rapidly improve the health of cows; however, changes in metabolism following surgery are rarely described. To investigate the changes of plasma metabolome in cows with LDA before and after surgical correction, blood samples were collected from 10 healthy postpartum cows and 10 cows with LDA on the day of diagnosis, then again from the LDA cows 14 d after surgery. Serum nonesterified fatty acid, ß-hydroxybutyric acid, cortisol and histamine concentration, and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities were evaluated, and the metabolic profile in plasma was analyzed using ultra-high-performance liquid chromatography time-of-flight mass spectrometry. The results demonstrated that cows with LDA experienced severe negative energy balance and oxidative stress, which can be improved by surgical correction. The metabolic profile was analyzed using multidimensional and univariate statistical analyses, and different metabolites were identified. In total, 102 metabolites differed between cows with LDA and healthy cows. After surgical correction, 65 metabolites changed in cows with LDA, compared with these cows during the LDA event. Following surgical correction, AA levels tended to increase, and lipid levels tended to decrease in cows with LDA. Pathway analysis indicated marked changes in linoleic acid metabolism, Arg biosynthesis, and Gly, Ser, and Thr metabolism in cows at the onset of LDA and following surgical correction. Surgical treatment reversed the changes in AA and lipid metabolism in cows with LDA.

[Diagnosis and endoscopic treatment of blunt laryngeal trauma with arytenoid injury].

Objective: To investigate the clinical characteristics, diagnosis, endoscopic surgical procedures, and therapeutic effect of blunt laryngeal trauma with arytenoid injury. Methods: We retrospectively reviewed 12 patients who suffered blunt laryngeal trauma with laryngeal mucosa avulsion and arytenoid region injury at the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital from April 2007 to December 2018. Among the 12 patients, 10 were males, 2 were females, aged from 7 to 48 years old, with a median age of 21 years old. All patients were performed with transoral endoscopic laryngeal microsurgery under general anesthesia. Clinical characteristics, laryngoscopic signs, laryngeal CT, endoscopic surgical findings and procedures, and therapeutic effect were analyzed. The subjective and objective parameters of the voice quality of patients before and after surgery were compared using SPSS 22.0 statistical software by paired T test. Results: All patients had a history of obvious dysphonia immediately after trauma, accompanied by throat pain and hemoptysis without obvious dyspnea and dysphagia. Slight subcutaneous emphysema was found in 3 patients by physical examination. Laryngoscope revealed that 14 sides of vocal folds immobilized, arytenoid and/or ventricular region and posterior glottis mucosa were avulsed in 4 patients within 48 h of injury, and arytenoid cartilage was exposed in 4 sides. The arytenoid and ventricular regions were covered with thick pseudo-membrane or granulation, with abnormal structure in 8 patients with damage of more than 48 h. Intraoperative exploration revealed that there were 17 sides of arytenoid region (bilateral 5 cases, unilateral 7 cases) with varying degrees of injury. There was only limited laceration on three sides of the vocal folds. The lateral ventricular and vocal fold mucosae were avulsed vertically from the arytenoid region and arytenoid cartilage was exposed in 14 sides, among which 6 sides had abnormal arytenoid cartilage morphology and 8 sides had fracture displacement. Laryngeal CT showed irregular thickening of lateral glottis and/or supratroglottic structures in patients with vocal folds immobility, among which asymmetry of arytenoid cartilage structure on both sides in 3 cases and displacement in 2 cases were found. Restoration and microsuture of the fractured arytenoid, perichondrium and avulsion laryngeal mucosa under the direct laryngoscope were performed. The degree of dysphonia was significantly improved immediately after laryngeal microsurgery, the voice significantly improved in G, R, B, A, jitter, shimmer, NHR, and MPT three months after surgery(t=12.792, 12.792, 10.340, 3.276, 2.865, 3.781, 3.173, 3.090, respectively, P<0.05). Except for 1 patient with scar on vocal fold, all the other patients had normal laryngeal morphology and normal vocal fold movement. No laryngeal stenosis was found during the follow-up period. Conclusions: For patients with blunt laryngeal trauma, the injury of arytenoid region and arytenoid cartilage should be evaluated if there is obvious hoarseness, vocal fold immobility, avulsion of ventricular/vocal folds mucosa, or structural abnormality of arytenoid region under laryngoscopic examination. For highly suspected cases, microrphonosurgery under the direct laryngoscope should be performed as soon as possible, which can effectively reduce the occurrence of vocal fold movement disorders and laryngeal scar/stenosis, reconstruct the normal laryngeal structure, and restore the vocal function.

Validation of reference genes for the normalization of RT-qPCR expression studies on human laryngeal cancer and hypopharyngeal cancer.

OBJECTIVE: Selecting stably expressed reference genes is crucial for evaluating real-time quantitative polymerase chain reaction (RT-qPCR) data via the relative quantification method. In the present-day study, our aim was to select optimal reference genes (RGs) for the investigation of target gene (TG) expression profiling in cancerous human laryngeal and hypopharyngeal tissues. PATIENTS AND METHODS: 12 cancerous laryngeal tissues and 10 cancerous hypopharyngeal tissues were investigated. The expression characteristics of 11 reference genes (18S rRNA, GAPDH, B2M, ACTB, TBP, ALAS1, RPL29, HMBS, HPRT1, GUSB, and PUM1), which were commonly used in RT-qPCR for the analysis of gene expression, were investigated using the geNorm, NormFinder, and BestKeeper algorithm programs. RESULTS: HMBS, ALAS1, and B2M were suggested as optimal RGs for studying human laryngeal and hypopharyngeal cancerous tissues together, laryngeal cancerous tissue by itself, and hypopharyngeal cancerous tissue by itself, respectively. If 2 or more reference genes are needed to achieve better standardization, 3 reference genes can optimally be used in combination to improve the accuracy of relative quantitation normalization. The recommended combinations for studying human laryngeal and hypopharyngeal cancerous tissues together, laryngeal cancerous tissue by itself, and hypopharyngeal cancerous tissue by itself were HMBS + HPRT1 + GUSB, ALAS1 + GUSB + HMBS, and B2M + HPRT1 + TBP, respectively. CONCLUSIONS: The recommended reference genes could be used to improve the accuracy of gene expression studies on the molecular mechanisms of cancerous human laryngeal and hypopharyngeal tissues. The selected combination of reference genes can effectively improve the accuracy of the relative quantitative diagnosis of gene expression levels, such as messenger RNA, circular RNA, and long-noncoding RNA.

[The expression characteristics and clinical significance of candidate molecular markers in vocal cord leukoplakia].

Objective: To investigate the expression of marker proteins in vocal cord leukoplakia, and to find markers for the early stage of diagnosis and prognosis of precancerous lesions. Methods: The study included 119 cases, 68 cases of vocal cord leukoplakia (22 cases with epithelial simple hyperplasia, 46 cases with epithelial dysplasia), and 51 cases of vocal cords benign lesions(31 cases of vocal cord polyps, 20 cases of Reinke's edema). The expression of p53, Ki-67, p21, Survivin, p16, p27, PTEN, c-Myc and vascular endothelial growth factor (VEGF) in vocal cords leukoplakia were detected, vocal cord benign lesions (vocal cord polyps and Reinke's edema) acted as controls, comparing the expression differences of different pathological tissue. Data was analyzed by SPSS 22.0 software. Results: The expression of p53, p16, Ki-67, VEGF in vocal cord benign lesions and vocal cords leukoplakia with epithelial simple hyperplasia did not show significant differences. There was a grading increase in the positive expression of p53, Ki-67 in the vocal cord leukoplakia with epithelial dysplasia contrasting to those in vocal cord benign lesions and vocal cords leukoplakia with epithelial simple hyperplasia (p53: χ(2)=13.340, P=0.002, Ki-67: χ(2)=53.386, P=0.000). The expression of p27, PTEN, c-Myc in vocal cord benign lesions and vocal cords leukoplakia with epithelial dysplasia did not show significant differences. There was a grading increase in the positive expression of p21 Survivin in vocal cords leukoplakia with epithelial dysplasia contrasting to those in vocal cord benign lesions (P<0.05). Expression of Survivin in vocal cords leukoplakia with mild-moderate epithelial dysplasia showed a significant increase than those in vocal cord benign lesions (P<0.05). The positive expression grade of p21 showed a rising trend (P=0.073) between the different grades of dysplasia. Conclusion: The positive expression grade of p53, Ki-67, p21 Survivin showed an increase in vocal cords leukoplakia with epithelial dysplasia contrasting to those in vocal cord benign lesions, which might be an implication for evaluating the diagnosis and prognosis of precancerous lesions. Expression of p21 was correlated to the degrees of dysplasia and expression of Survivin showed a significant difference in early stage of epithelial dysplasia contrasting to benign lesions.

[A retrospective analysis of CO(2) laser and microdebrider for the treatment of severe juvenile on-set recurrent respiratory papillomatosis].

Objective: Juvenile on-set recurrent respiratory papillomatosis (JORRP) can be an aggressive and potentially life-threatening disease. To emphasize the importance of complication prevention in local excision surgery, the single-center experience of RRP treatment in a group of patients with relatively short recurrence-free-interval (>4 times/yrs) was reported. Methods: Data of 49 patients underwent papilloma resection during 2002-2013 were retrospectively analyzed. Combined techniques of laser microsurgery and microdebriders were used to remove papillomas, prevent the formation of scar tissue and improve respiratory distress. Forty-nine cases were followed up for 99.0[74.5; 121.0]months, ranging from 39 to 185 months. The age of disease onset was 2[1; 3] years old. Most of the patients had difficulty in breathing(42 of 49 cases). Seven patients had hoarseness.53.0% patients had subglottic or trachea papillomatosis spreading. The rate of complications, synechia formation, tracheal stenosis, needing for tracheostomy, mortality was recorded. Patients were followed up for at least three years. The characteristics of the patients, improvement in symptoms, recurrence-free interval, and the rate of tracheal extubation were evaluated. Wilcoxon signed ranks test and chi-square test were used for data comparation. Results: Long-term relieve in disease(≤2 surgeries were needed/year) were achieved in 29(59.1%) subjects, in which 8(16.3%) of the subjects did not need surgical treatment for at least 3 years. Long-term relieve had been achieved in 25 of subjects who did not accept tracheostomy. Seven subjects did not need surgical treatment for at least 3 years. The rate of successful tracheal extubation was 53.8% in 13 patients who had undergone tracheostomy. Three cases dead of intrapulmonary spread. Conclusions: Combined techniques of laser microsurgery and microdebriders are effective in improvement in both respiratory distress and voice quality. The combined technique are helpful to avoid inevitable long-term stenotic complications, ultimately affecting the quality of life.

[Laryngotracheal resection and reconstruction for the treatment of acquired laryngotracheal stenosis].

Objective: To analyze the efficacy of laryngotracheal resection and reconstruction for acquired laryngotracheal stenosis, and to discuss the prevention of complication. Methods: The clinical outcomes of seventy patients with acquired laryngotracheal stenosis, treated with laryngotracheal resection and reconstruction were retrospectively reviewed between January 2007 and December 2016. The degree of stenosis was classified according to Myer-Cotton classification as follows: grade Ⅱ(n=7), grade Ⅲ(n=38) and grade Ⅳ(n=27). The stenostic extension ranged from 0.5-4.0 cm (median 2.0 cm), the resection extension ranged from 1.0-5.0 cm (median 3.0 cm). Fifty-three stenosis originated from iatrogenic (endotracheal tubes and/or tracheostomy), 17 originated from cervical trauma. Results: Thirty patients were treated by the resection of tracheal and primary anastomosis. Twenty-nine patients were treated by resection and reconstruction and supported by T-tube. Eleven patients with subglottic stenosis were treated by complete resection of tracheal lesion and the arch of cricoid cartilage, together with trachea and thyroid cartilage anastomosis with tracheotomy. Six months after surgery, the outcome was good to satisfactory in 65 patients (92.9%). Five patients failed(3 were tracheotomized and 2 were supported by T-tube). Complications included granulation tissue formation(n=15), anastomoticseparation(n=9), restenosis of anastomosis(n=9), wound infection(n=5) and subcutaneous emphysema(n=7). In 15 patients with granulation tissue, 10 patients needed endoscopic resection, and 5 patients resulted in anastomotic stenosis. No injury to recurrent laryngeal nerve was found. Three patients with trachoesophageal fistula were repaired. Conclusion: Laryngotracheal resection and reconstruction is an effective surgical method for acquired laryngotracheal stenosis, which has a higher successful rate and shorter therapeutic period.

Evaluation of the stability of reference genes in bone mesenchymal stem cells from patients with avascular necrosis of the femoral head.

This study aimed to evaluate 12 genes (18S, GAPDH, B2M, ACTB, ALAS1, GUSB, HPRT1, PBGD, PPIA, PUM1, RPL29, and TBP) for their reliability and stability as reference sequences for real-time quantitative PCR (RT-qPCR) in bone marrow-derived mesenchymal stem cells (BMSCs) isolated from patients with avascular necrosis of the femoral head (ANFH). BMSCs were isolated from 20 ANFH patients divided into four groups according to etiology, and four donors with femoral neck fractures. Total RNA was isolated from BMSCs and reverse transcribed into complementary DNA, which served as a template for RT-qPCR. Three commonly used programs were then used to analyze the results. Reference gene expression varied within each group, between specific groups, and among all five groups. Based on comparisons of all five groups, two of the programs used suggested that HPRT1 was the most stable reference gene, while 18S and ACTB were the most variable. Among the 12 candidate reference genes, HPRT1 exhibited the greatest reliability, followed by PPIA. Thus, these sequences could be used as references for the normalization of RT-qPCR results.

[Clinical and pathological characteristics of vocal fold leukoplakia and influential factors of recurrence and malignancy].

Objective:To investigate the clinical and pathological characteristics of vocal fold leukoplakia and influential factors of recurrence and malignancy. Method:The study included 555 cases of vocal fold leukoplakia. All patients received surgical treatment. The relationship between the clinical and pathological features, and influential factors of recurrence and malignancy were analyzed. Result:The pathological types included squamous epithelial simple hyperplasia in 58.0%, mild hyperplasia in 15.5%, moderate hyperplasia in 10.1%, severe hyperplasia and carcinoma in situ in 8.1%, infiltrative carcinoma in 8.3%. The different pathological types varied among different ages significantly(P<0.01). The tobacco and alcohol abuse had no relationship with pathological types(P>0.05). The more severe the pathology were, the more decreasing of the mucosal waves would be(P<0.01). The pathologic severity had an apparent correlation with p53 positivity and the level of p53 and Ki67 positivity. The p53 positive proportion may increase with the increasing pathological severity(P<0.01), so were the p53 and Ki67 positive levels(P<0.01).Among 232 cases of postoperation follow-ups, 83 cases(35.8%) relapsed while 8 cases(3.4%) malignancy. Bilateral lesions had a higher rate of relapse and malignancy than unilateral lesions(95%CIOR 0.378 ［0.197-0.723］，P<0.01). The relapse and malignancy had a relationship with the pathologic severity. The incidence of disease recurrence and malignancy were positively correlated with pathological severity(P<0.05). p16 positive patients relapsed for more times(P<0.01) and with an uprising tendency of relapse and malignancy（P>0.05）. Conclusion:Pathological types of vocal fold leukoplakia are different. The older men, decreasing of mucosal wave of vocal folds and bilateral lesions were very important factors to predict disease severity. p53 and Ki67 positive rating and pathological severity were positively correlated. The bilateral lesions, pathological severity and p16 positivity had a tendency to increasing relapse and malignancy.

[Expression of EGFR in keratosis of laryngeal and the correlation with malignant phenotype].

OBJECTIVE: To evaluate the roles of EGFR expression in laryngeal keratosis. METHOD: The ABC immunohistochemical method was performed to investigate the expression of EGFR in 32 cases of laryngeal keratosis tissue. RESULT: The EGFR indices in light, moderate and serious non-typical hyperplasia were 12.5%, 22.5% and 47.8% respectively. There were significant differences between heavy with light and middle non-typical hyperplasia (P < 0.05). CONCLUSION: The EGFR might play some role in the process of carcinogenesis of laryngeal keratosis, and be as an useful marker for the assessment of the behavior and prognosis in the laryngeal premalignant lesions keratosis.