[Effects of preoperative quetiapine on postoperative delirium and sleep quality in elderly orthopaedic patients].

Objective: To investigate the effects of preoperative quetiapine on postoperative delirium (POD) and sleep quality in elderly orthopedic patients. Methods: Prospectively, 111 elderly patients, American Society of Anesthesiologists (ASA) grade Ⅱ-Ⅲ, scheduled to undergo knee or hip surgery in the Affiliated Huangyan Hospital of Wenzhou Medical University under continuous spinal anesthesia from August 2021 to March 2023, were selected and randomly divided into two groups by random number table: control group (group C, 1 h preoperative placebo) and quetiapine group (group Q, 1 h preoperative quetiapine 12.5 mg). In group C, 54 cases were enrolled, including 25 males and 29 females, with an average age of (73.5±4.9) years. In group Q, 57 cases were enrolled, including 26 males and 31 females, with an average age of (74.8±5.0) years. The primary outcome measures were the incidence of POD evaluated by using confusion assessment method (CAM) at 24, 48, and 72 hours after surgery, and the secondary outcome measures included Pittsburgh sleep quality index (PSQI) scores at 24 and 48 hours after surgery and satisfaction of pain management within 24 hours after surgery. Results: The incidence of POD at 24, 48, and 72 h after surgery in group Q was 5.4% (3/57), 12.5% (7/57), 14.3% (8/57), respectively, while that in group C was 18.2% (10/54), 21.8% (12/54), 21.8% (12/54), respectively. The incidence of POD at 24 h after surgery in group Q was lower than that in group C (P=0.036). There was no significant difference in the incidence of POD at 48 and 72 h after surgery between two groups (all P>0.05). The PSQI score of patients in group Q at 24 and 48 h after surgery were (3.8±1.2) and (6.9±1.1) scores, respectively, which in group C were (10.5±2.8) and (7.3±1.3) scores, respectively. Compared with group C, the PSQI score of patients in group Q at 24 h after surgery was significantly higher (P<0.001), but there was no significant difference at 48 h after surgery (P=0.068). The satisfaction scores of pain management at 24 h after surgery in group Q was (91±7) scores, which was higher than that in group C of (81±6) scores (P<0.001). Conclusion: Oral intake of low-dose quetiapine 1 h preoperatively can reduce the incidence of POD, improve postoperative sleep quality and enhance postoperative satisfaction of pain management at 24 hours after surgery in elderly orthopedic patients undergoing knee or hip surgery.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[Clinical characteristics of Danon disease].

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

[Hepatitis C elimination among drug users in China: challenges, strategies and experiences].

The prevalence of hepatitis C among drug users in China is high, and thus it is one of the populations that needs attention to achieve hepatitis C elimination. However, due to the complexities of this population's situation, hepatitis C elimination still faces many challenges, such as difficult screening, low cure rate, poor compliance, and high reinfection rates. Therefore, the existing diagnostic and therapeutic system cannot meet the needs of this population. China has pledged to establish a unified system for drug users that will integrate drug treatment programs, education, medical care, and rehabilitation, creating favorable conditions for integrating hepatitis C diagnosis and treatment and improving the accessibility of drug users. Starting with the current situation and challenges of eliminating hepatitis C among drug users in China, in combination with cases from other countries, this paper discusses the strategy for eliminating hepatitis C and introduces what Hainan Province did to eliminate hepatitis C among drug users.

[Measuring laryngotracheal stenosis by extracting centerline based on CT 3D reconstruction].

Objective: To compare the accuracy of the centerline extracted based on CT 3D reconstruction and conventional CT 3D reconstruction in measuring the length and degree of laryngotracheal stenosis. Methods: A retrospective analysis was performed on 35 patients with laryngotracheal stenosis (including 19 cases without tracheotomy and 16 cases with tracheotomy) treated in the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Guangxi Medical University from March 2006 to March 2016, including 20 males and 15 females, whose ages ranged from 1 to 73 years, with a median age of 40.5 years. And CT data of 20 normal subjects were included in the same period, including 10 males and 10 females, whose ages ranged from 20 to 63 years, with a median age of 37.0 years. The continuous cross-sectional area of the airway perpendicular to the centerline was obtained by Mimics software. The area was compared with the discontinuous cross-sectional areas reconstructed by conventional CT 3D reconstruction software advantage workstation, also the length of cervical trachea, the length of stenosis, and the minimum airway area were compared. Multi-factor linear stepwise regression method was used to analyze the factors influencing the measuring difference between the two methods. Three patients with laryngotracheal stenosis were selected, and the measured stenosis length was compared with the surgical specimens to evaluate the accuracy of the two methods. SPSS 26.0 software was used for statistical analysis. Results: In normal people, the areas of thyroid cartilage notch, glottis, inferio thyroid cartilage margin, inferio cricoid cartilage margin, and suprasternal notch planes measured by Mimics centerline method were smaller than those measured by conventional CT 3D reconstruction (t thyroid cartilage notch=4.685, tglottis=3.791, tlower thyroid cartilage margin=5.621, tlower cricoid cartilage margin=6.312, tsuprasternal notch plane=6.436, P<0.05). And the airway length measured by Mimics centerline method from the inferior thyroid cartilage to the superior sternal notch was longer (t=9.79, P<0.001). In laryngotracheal stenosis, in the non-tracheotomy group, the minimum airway area measured by Mimics centerline method was smaller and the stenosis length was longer than those measured by the conventional CT 3D reconstruction, and the difference was statistically significant (tminimum airway area=2.562, tstenosis length=5.240, P<0.05). In the tracheotomy group, the stenosis length measured by Mimics centerline method was longer than that measured by conventional CT 3D reconstruction, and the difference was statistically significant (tstenosis length=2.854, P<0.05). Multi-factor linear regression analysis showed that different CT thickness had a statistically significant effect on the difference in the length of stenosis measured by the two methods (b=-5.370, t=-3.306, P=0.004), and different tracheal forward angle had a statistically significant effect on the difference in the minimum airway area measured by the two methods (b=-0.419, t=-2.208, P=0.04). The difference between the measured length of the Mimics centerline method and the intraoperative specimens was less than 0.5 mm. Conclusion: The centerline extracted based on CT 3D reconstruction can precisely reflect the laryngotracheal morphology and measure laryngotracheal stenosis more accurately.

[Malignant solitary fibrous tumors: a clinicopathological and molecular genetic analysis].

Objective: To explore the clinicopathological features, immunophenotype and molecular genetic characteristics of malignant solitary fibrous tumor (MSFT). Methods: Seven cases of MSFT were collected from the First Affiliated Hospital of Zhengzhou University from July 2018 to December 2020. Immunohistochemistry, RNA-based NGS and DNA-based NGS were performed. Results Among the 7 patients, there were 5 males and 2 females with a median age of 53 years (37-69 years). Two tumors located at skull base, and one in the tentorium of cerebellum, parietal occipital region, occipital area, chest and buttock respectively. The maximum diameter of the tumor was 2.5-20.0 cm. Microscopically, typical hemangiopericomatoid structures were noted; the tumor was cellular, fusiform or oval, very pleomorphic, with necrosis and high mitotic figures (>4/10 HPF). In some cases, classical solitary fibrous tumor morphology and dedifferentiated region were observed. Immunohistochemically, the tumor was positive for CD34 (6/7), STAT6 (7/7), bcl-2 (7/7), but negative for S-100 (7/7); CKpan or EMA was positive to varying degrees; mutated p53 was noted (3/7); Ki-67 positive index was more than 10%. NAB2-STAT6 gene fusion was typically detected in all the 7 cases. In 4 cases, ZNF415-FGFR1, COPG1-MET, IPO11-LRRC70_ncRNA-PLAG1 and Clorf198-CD274 (PD-L1) gene fusions were also detected. NOTCH1 mutation was found in 7 cases and TP53 mutation in 4 cases. TERT promoter mutations were not detected in all the cases. Conclusions: MSFT is rare and needs to be differentiated from many other spindle cell tumors. Especially when tumors express epithelial markers, they are easily misdiagnosed as sarcomatoid carcinoma and synovial sarcoma, etc. Immunohistochemistry and molecular detection of NAB2-STAT6 gene fusion have important diagnostic values. NOTCH1 and TP53 mutations may be associated with the progression of MSFT. Some patients have FGFR1 gene fusion and MET gene fusion, which may be potential therapeutic targets.

[Impact and clinical value of the revised 2019 Chinese HER-2 testing guidelines on the detect result evaluation of invasive breast cancer cases with equivocal HER-2 immunostaining by using fluorescence in situ hybridization].

Objective: To investigate the impact and clinical significance of the revised 2019 Chinese HER-2 testing guidelines on the detecting result evaluation of invasive breast cancers with equivocal HER-2 immunostaining by using fluorescence in situ hybridization (FISH). Methods: A total of 569 cases of invasive breast cancers with HER-2 (+ + ) immunostaining evaluated according to the immunohistochemistry (IHC) guidelines of 2014 edition and 2019 edition from May to November 2019 were collected and further detected by FISH. The results of HER-2/CEPl7 double probe were respectively interpreted according to both the 2014 and 2019 Chinese HER-2 testing guidelines and the results were compared. Results: According to the 2014 guidelines, the number of HER-2 positive, equivocal and negative cases were 139 (24.43%), 67 (11.78%), and 363 (63.80%), respectively. Whereas according to the 2019 guidelines, 115 cases (20.21%) were the first group, 9 cases (1.58%) were the second group, 15 cases (2.64%) were the third group, 67 cases (11.78%) were the fourth group, and 363 cases were (63.80%) the fifth group, of which 130 cases (22.85%) were positive and 439 cases (77.15%) were negative by FISH detecting. Compared with the guideline of 2014 edition, the HER-2 positive rate of FISH detection reduced from 24.43% (139/569) to 22.85% (130/559) according to the application of the guideline of 2019 edition, but the difference was not statistically significant (P=0.567), while the negative rate increased from 63.80% (363/569) to 77.15% (439/569), with a statistically significant difference (P<0.05). Forty-three cases with incomplete weak to medium intensity of IHC membrane staining which were HER-2 (+ + ) according to 2014 guideline were changed to IHC (+ ) on the basis of the 2019 guideline. According to the FISH guideline of 2014 edition, 1 case (2.33%) was positive, 6 cases (13.95%) was equivocal and 36 cases (83.72%) was negative, while according to the 2019 FISH guideline, all of the 43 cases were negative. Conclusions: According to the guideline of 2019 edition, a proportion of cases changes from HER-2 (+ + ) to (+ ), and the HER-2 positive rate of FISH test decreases slightly, the negative rate increases, the equivocal result is eliminated, which provides a definite reference for screening patients who will be benefited from the targeted treatment of HER-2.

[Multicenter cross-sectional investigation on the cleaning status and influencing factors of skin cleaning outside the wound in adult trauma patients].

Objective: To investigate the status and influencing factors of skin cleaning outside wound (hereinafter referred to as skin) in adult trauma patients. Methods: A multicenter cross-sectional investigation was conducted. From September 1 to 30, 2020, a total of 952 adult trauma patients who met the inclusion criteria were admitted to wound care clinics or trauma surgery wards of 13 military or local Grade Ⅲ Level A hospitals, including the General Hospital of the Eastern Theater Command of People's Liberation Army and the Army Medical Center, etc. A self-designed questionnaire on cleaning status of skin in trauma patients was released through the "questionnaire star" website to investigate basic information such as gender, age, education level, living status, and self-care ability, trauma information such as cause of injury, wound duration, trauma site, trauma depth, wound pain, wound peculiar smell, and wound cleaning solution, and skin cleaning status after injury such as whether to clean or not, cleaning method, cleaning frequency, cleaning duration in each time, or reasons for not cleaning. The patients who cleaned skin regularly after injury were included in cleaning group, and the other patients were included in no cleaning group. The basic information, trauma information, and skin cleaning status after injury of patients in 2 groups were investigated. Data were statistically analyzed with chi-square test, and binary multivariate logistic regression analysis was performed on indicators with statistically significant differences between the two groups to screen the independent influencing factors of skin cleaning in trauma patients. Results: A total of 952 questionnaires were received, and the recovery rate was 100%. Three invalid questionnaires were eliminated, and 949 valid questionnaires were obtained, with an effective rate of 99.68%. In 949 patients, there were 461 (48.6%) males and 488 (51.4%) females, aged 18-100 (50±18) years. Most patients were less than 60 years old, lived with their families, and could take care of themselves completely. Nearly half of the patients were with junior high school or below education level. The main causes of injury were sharp cutting injury and falling injury, the wound duration was 2-365 days, most of the injured parts were limbs and trunk, the wound depth was mostly full-thickness injury, and most patients had wound-related pain and no peculiar smell and used 5 g/L iodophor to clean the wound. Totally 684 (72.1%) patients cleaned their skin after injury, mainly by scrubbing with warm water, the cleaning frequency was mainly once or twice a week, and the cleaning time was mainly 10 or 15 min for each time. Totally 265 (27.9%) patients didn't clean their skin after injury, and the main causes for not cleaning were following the doctor's advice, followed by worrying about wound infection and loss of self-care ability. There were significantly statistical differences in constituent ratios of education level, self-care ability, cause of injury, wound pain, and wound peculiar smell of patients in 2 groups (χ2=12.365, 24.519, 22.820, 9.572, 92.342, P<0.01). Education level, self-care ability, cause of injury, wound pain, and wound peculiar smell were potential influencing factors of skin cleaning in patients. Binary multivariate logistic regression analysis showed that self-care ability, wound pain, and wound peculiar smell were independent influencing factors of skin cleaning in patients (odds ratio=1.51, 0.52, 3.72, 95% confidence interval=1.08-2.12, 0.42-0.89, 2.66-5.22, P<0.05 or P<0.01). Conclusions: Self-care ability, wound pain, and wound peculiar smell are independent influencing factors of skin cleaning in adult trauma patients.

[Diagnostic value of diffusion-weighted imaging and conventional magnetic resonance imaging in testicular tumor].

Apparent diffusion coefficient(ADC) of magnetic resonance imaging≤0.90×10-3 mm2/s and T2-hypointensity, intratuminal septa, and peritumoral infiltration could achieve best diagnostic efficiency. ADC values and cyst or necrosis were independent predictors for the differential diagnosis of nonseminomatous germ cell tumor versus seminoma and nonseminomatous germ cell tumor versus lymphoma. ADC value and intratuminal septa were independent predictors for the differential of seminoma versus lymphoma.

[Analysis of gene mutation profile of adult soft tissue sarcomas using high-throughput sequencing technology].

Objective: To understand the genetic variation of soft tissue sarcomas, and to provide a scientific evidence for the individualized treatment. Methods: The somatic mutation and germline mutation of 45 adult soft tissue sarcomas had been detected by high-throughput sequencing technology, the clinical data were also analyzed. Results: A total of 88 gene mutations were detected in 45 samples, including 78 single nucleotide variation (SNV), 13 insertion/deletion (Indel) and 19 copy number variation (CNV). The most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN. Among them, the mutation rates of TP53-MDM2/MDM4-CDKN2A pathway, CDKN2A/CDK4/RB1 pathway, and RAS/NF1/PTEN/PI3K pathway were more frequent (32/88, 36%). In terms of immunotherapy biomarkers among 10 samples, the median value of tumor mutation burden was 2.02 muts/Mb (0-4.24 muts/Mb), and all were microsatellite stable. Conclusions: This study analyzes the genetic variation of soft tissue sarcoma, and determines the high-frequency gene mutations and pathways, which may be the potential drug targets. This finding can provide scientific evidences for the personalized treatment of soft tissue sarcoma.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

[Analysis of clinical, pathological features and therapeutic treatments in predicting prognosis of elderly glioblastomas].

Objective: This study was designed to investigate prognostic factors and the potential relationship between the expression of Ki67 and IDH of glioblastoma in the elderly (≥ 65 years old) and the clinical factors such as gender, the KPS score and treatments including surgical resection, radiotherapy and chemotherapy and the prognosis of such patients. Methods: Fifty-four elderly patients (≥ 65 years old) with glioblastoma admitted to the First Affiliated Hospital of Zhengzhou University from 2013 to 2018 were enrolled in this study. The expression of Ki67 was detected by immunohistochemical SP method and the mutation of IDH was detected by Sanger sequencing. Finally, statistical analysis was performed to determine whether Ki67, the mutation of IDH, gender, the KPS score and the extent of resection, radiotherapy and chemotherapy were associated with the clinical prognosis of the patients. Results: Of the 54 elderly patients with glioblastoma, none was detected with IDH mutation. Univariate analysis showed that Ki67(P=0.033), the KPS score (P=0.008), the extent of resection (P<0.001) were factors influencing the prognosis of elderly patients with glioblastoma. Patients receiving postoperative adjuvant radiotherapy (P=0.002) and chemotherapy (P=0.034) had longer survival time. There was no significant correlation between gender (P=0.467) and prognosis. Multivariate analysis demonstrated that radiotherapy (OR 2.446, P=0.009) and the extent of resection (OR 6.976, P<0.001) were independent prognostic factors. Conclusions: No IDH mutation was detected in all the patients in this study, indicating that IDH mutation is indeed rare in elderly glioblastoma, which suggests that geriatric population often harbor a molecular phenotype with poor prognosis. Ki67, KPS score, the extent of resection, radiotherapy and chemotherapy were the factors influencing the prognosis of patients.

[Consistency of ALK Ventana-D5F3 immunohistochemistry interpretation in lung adenocarcinoma among Chinese histopathologists].

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer's protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion: There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

[Analyses of diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations].

Objective: To investigate the key issues in the diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations. Methods: A retrospective study was performed for 11 pediatric patients who were treated in Department of Otorhinolaryngology and Head and Neck Surgery, Henan Province People's Hospital after a diagnosis of foreign body aspiration with tracheobronchial variations between January 2015 and December 2017. There were 7 males and 4 females among the 11 cases of foreign body aspiration with tracheobronchial variations, ranging between 9 months and 11 years of age. Results: Among 11 cases, the types of variationswere tracheal bronchus in 9 cases, bridging bronchus in 1 case and simple tracheal stenosis in 1 case. All of the pediatric patients were under general anesthesia, and the foreign bodies were removed by bronchoscopy successfully with no significant complications. Conclusions: The possibility of tracheobronchial variations should be considered in children with recurrent wheezing and poor efficacy of regular treatment before foreign body aspiration. Removal of foreign body via rigid bronchoscope under general anesthesia is a safe and effective treatment. These children are needed to combine the situation oftracheobronchial variations and the location of foreign bodies to guide the operation, and strengthened the perioperative treatment.

TSLP regulates eotaxin-1 production by nasal epithelial cells from patients with eosinophilic CRSwNP.

BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by Th2-skewed inflammation with eosinophilic infiltration. Thymic stromal lymphopoietin (TSLP) promotes the development of allergic inflammation. Although increased TSLP is found in eCRSwNP, little is known about whether TSLP regulates eotaxin-1 production, a potent eosinophil chemoattractant that recruits and activates eosinophils. OBJECTIVE: The aim of this study was to investigate the effects and mechanisms of TSLP in eotaxin-1 production in the eosinophilic inflammation of eCRSwNP. METHODS: Human nasal epithelial cells (HNECs) from eCRSwNP patients were stimulated with recombinant human TSLP in the presence or absence of CYT387 (Janus kinase 1/2 inhibitor). Phosphorylated signal transducer activator of transcription 3 (p-STAT3) was measured by using immunocytochemistry. Eotaxin-1 expression was determined by using real-time PCR. Western blotting was used to detect the levels of p-STAT3 and eotaxin-1 protein. RESULTS: The treatment with TSLP induced STAT3 phosphorylation in HNECs, and promoted p-STAT3 nuclear translocation, leading to a time-dependent increase of eotaxin-1 expression. However, these effects were attenuated by CYT387 pretreatment. CONCLUSION: TSLP regulated eotaxin-1 production in HNECs via JAK1/2-STAT3 signaling, which might contribute to the eosinophilic inflammation of eCRSwNP.

[Downregulated PI3K-Akt-eNOS expression is related to increased atrial fibrillation inducibility in diabetic rats].

Objective: To explore the impact of PI3K-Akt-eNOS signaling on atrial fibrillation inducibility in diabetic rats. Method: Eight-week-old male diabetic rats were randomized assigned into GK group, IGF group and L-NAME group (n=8 each) which respectively received normal saline (NS), insulin like growth factor (IGF-1) or L-NAME+IGF-1 through tail vein daily for 4 weeks. Eight 8-week-old male homologous Wister-Kyoto(WKY) rats treated with intravenous NS served as control group (WKY group). Blood glucose was measured once per week. The left atrial diameter (LAD) was measured by echocardiography, the atrial electrical parameters, including the P-wave duration, the atrial effective refractory period (AERP) and its dispersion (AERP-d), the incidence and the duration of atrial fibrillation induced by atrial burst pacing, were evaluated by electro-physiological instrument at 4 weeks post various treatments. Rats were then sacrificed, left atrial (LA) cell morphology was determined on HE stained sections, LA interstitial collagen was determined on Masson stained sections. The protein expression of phosphatidylinositol 3-kinase (PI3K) and phosphate endothelial nitric oxide synthase (p-eNOS) were detected by Western blot. Results: (1) At the beginning of the study, the random blood glucose (GLU) level was significantly higher and LAD was large in GK, IGF and L-NAME groups than in WKY group;after 4 weeks, GLU level and LAD dimension of IGF group were lower than GK and L-NAME groups (P<0.01 or 0.05). (2) One rat in L-NAME group died during operation. Four weeks later, the incidence of atrial fibrillation in GK group, IGF group, L-NAME group and WKY group was 7/8, 2/8, 6/7 and 3/8. The median duration of atrial fibrillation in GK group, IGF group, L-NAME group and WKY group was 11.9(9.3, 13.1), 0(0, 1.8), 11.5(4.4, 12.0), and 0(0, 3.0) s. Compare with WKY group, the P-wave duration and PR interval were significantly longer, AERP-d, incidence, and duration of atrial fibrillation were significantly higher in GK group (P<0.01), these changed were significantly reversed in IGF group compared to GK and L-NAME groups (all P<0.01). Heart rate and AERP were similar among the 4 groups on (P>0.05). (3) Four weeks later, the CSA and CVF of LA were significantly larger in GK group than in WKY group (P<0.01), which were significantly reversed in IGF group (P<0.01 vs. GK group), and the beneficial effects of IGF disappeared by co-treatment with L-NAME (P<0.01 vs. IGF group). (4) Four weeks later, compare with WKY group, the protein expression of PI3K (P<0.01) and p-eNOS (P<0.05) of LA were significantly downregulated in GK group, which could be significantly upregulated by IGF (P<0.01 and 0.05 vs. GK group), these effects diminished by co-treatment with L-NAME (P<0.01 or 0.05 vs. IGF group). Conclusion: Increased atrial fibrillation susceptibility in diabetic rat is linked with structural and electrical remodeling in LA, possibly mediated through downregulated PI3K-Akt-eNOS signaling.

Highly expressed long non-coding RNA DUXAP10 promotes proliferation of ovarian cancer.

OBJECTIVE: To investigate the expression of long non-coding RNA DUXAP10 in ovarian cancer and its effect on ovarian cancer cell lines HO8910 and A2780 cells. MATERIALS AND METHODS: Search the microarray dataset from the Gene Expression Omnibus (GEO) database using the keywords "ovarian cancer" and "GPL570". The differentially expressed genes in ovarian cancer tissues and normal ovarian tissues were analyzed by bioinformatics. Normal ovarian epithelial cells IOSE386, ovarian cancer HEY, HO8910 and A2780 cell lines were cultured. Cell proliferation assay was detected by CCK8 method and cloning formation assay was done. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of RNA. RESULTS: The results showed that the expression of DUXAP10 in ovarian cancer tissues was significantly higher than that in normal ovarian tissues, which was consistent with those of TCGA. Clinical data analysis showed that the expression level of DUXAP10 was correlated with tumor size and FIGO stage in clinical patients. Compared with the negative control group, the proliferation ability and cell cloning ability of HO8910 cells overexpressing DUXAP10 were significantly increased (p<0.001), while the proliferation and cell cloning ability of A2780 cells interfering with DUXAP10 were significantly decreased (p<0.001), indicating that DUXAP10 played a role in promoting the proliferation of ovarian cancer cells. CONCLUSIONS: DUXAP10 was significantly overexpressed in ovarian cancer tissues, and its expression was positively correlated with tumor size and FIGO stage in clinical patients. DUXAP10 promoted the proliferation of ovarian cancer cells and was expected to be a predictor and a potential therapeutic target of ovarian cancer.

Sex differences in associations between blood lipids and cerebral small vessel disease.

BACKGROUND AND AIMS: Dyslipidemia predicts higher risk of coronary events and stroke and might be associated with cerebral small vessel disease (SVD). Previous studies linking blood lipids and SVD have yielded inconsistent results, which may be attributable to sex differences in lipids metabolism. The aim of this study was to investigate the relationships between blood lipids and SVD in neurologically healthy men and women. METHODS AND RESULTS: Consecutive 817 people aged 50 years or more were enrolled and underwent magnetic resonance imaging scans to evaluate the periventricular white matter lesions (PVWMLs), deep white matter lesions (DWMLs) and silent brain infarction (SBI). Fasting total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, apolipoprotein A-1 (apoA-1) and apolipoprotein B were assessed. Multivariable logistic regression analyses were performed to determine the associations of blood lipids with PVWMLs, DWMLs and SBI. HDL-C (for PVWMLs: OR 0.36, 95% CI 0.19-0.71; for DWMLs: OR 0.35, 95% CI 0.20-0.63) and apoA-1 (for PVWMLs: OR 0.27, 95% CI 0.11-0.66; for DWMLs: OR 0.22, 95% CI 0.10-0.48) were inversely associated with the severity of PVWMLs and DWMLs in women but not in men after adjustment for age, hypertension, diabetes, current smoking, daily drinking, body mass index and uric acid. Additionally, no blood lipids were significantly associated with SBI. CONCLUSIONS: Our findings demonstrate that sex differences may exist in the associations between lipids and SVD. HDL-C and apoA-1 levels were inversely associated with the severity of PVWMLs and DWMLs in women.