Alzheimer''s disease (AD) has brought to us huge medical and economic burdens, and so discovery of its therapeutic drugs is of great significance.In this paper, we utilized knowledge graph embedding (KGE) models to explore drug repurposing for AD on the publicly available drug repurposing knowledge graph (DRKG).Specifically, we applied four KGE models, namely TransE, DistMult, ComplEx, and RotatE, to learn the embedding vectors of entities and relations on DRKG.By using three classical knowledge graph evaluation metrics, we then evaluated and compared the performance of these models as well as the quality of the learned embedded vectors.Based on our results, we selected the RotatE model for link prediction and identified 16 drugs that might be repurposed for the treatment of AD.Previous studies have confirmed the potential therapeutic effects of 12 drugs against AD, i.e., glutathione, haloperidol, capsaicin, quercetin, estradiol, glucose, disulfire, adenosine, paroxetine, paclitaxel, glybride and amitriptyline.Our study demonstrates that drug repurposing based on KGE may provide new ideas and methods for AD drug discovery.Moreover, the RotatE model effectively integrates multi-source information of DRKG, enabling promising AD drug repurposing.The source code of this paper is available at https://github.com/LuYF-Lemon-love/AD-KGE.

Objective:To investigate the clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus.Methods:Fifty-two cases of basal cell layer type high-grade squamous dysplasia of the esophagus were collected at PLA Joint Logistics Support Force 989 Hospital (34 cases) and Beijing Chaoyang Hospital (18 cases) from 2009 to 2019. The clinical, histological and immunohistochemical features were characterized. Related literature was also reviewed.Results:The median age of the 52 patients was 64 years (range 43-72 years). There were 35 men and 17 women, with a male to female ratio of 2.1∶1.0. There were 8 cases in the upper esophagus, 41 in the middle esophagus and 3 in the lower esophagus. According to the Paris Classification, 24 cases were 0-Ⅱb and 28 cases were 0-Ⅱc. Endoscopic examination showed that the color of the lesions was red and the edge was irregular. The narrow band imaging showed that the lesions were brown, and the microvascular abnormalities on the mucosal surface were observed with high magnification. Iodine staining of the lesions showed no or light staining and irregular border. Histologically, the basal layer of squamous epithelium was hypercellular, with large and hyperchromatic nuclei, and disordered cell arrangement. A high proportion of the cases showed a down-growth pattern and associated invasive squamous cell carcinoma. The immunohistochemical staining of 37 cases showed that the mutation rate of p53 was 48.6% (18/37), the median of Ki-67 labeling index was 60% (range 20%-90%), the median of Ki-67 labeling index of the basal tumor cells was 26/HPF (range 5-70/HPF), and the rate of abnormal Ki-67 distribution pattern was 37(100.0%). According to the initial pathological diagnosis, there were 8 cases of low-grade intraepithelial neoplasia, 2 cases of atypical epithelial cells and 42 cases of high-grade intraepithelial neoplasia.Conclusions:The basal cell layer type high-grade squamous dysplasia of the esophagus has a unique morphology. The dysplasia is mainly limited to the lower half part of the squamous epithelium. With marked cytological atypia and prominent invasiveness pattern, it is likely to develop into invasive squamous cell carcinoma at an early stage of the disease. The rate of pathologic misdiagnosis (such as low-grade lesion) is high. The p53 mutation and Ki-67 abnormal distribution pattern are helpful features for confirming the diagnosis of such high-grade dysplasia.

Objective: To compare T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) in the patients with coexistence of HBsAg and HBsAb and other HBV infected patients. Methods: The clonotype and diversity of CDR3 in blood of group cases (positive HBsAg and HBsAb) (n=11), control 1 (negative HBsAg and positive HBsAb) (n=10) and control 2 (positive HBsAg and negative HBsAb) (n=10) were analyzed by high-throughput TCR sequencing with Illumina HiseqX10. Results: In the case group, the overlap rate of 6.28% (0.25%, 13.10%) was detected between any two samples, which was significantly lower than the overlap rate of 10.49% (6.20%，17.30%) seen in control 1 group (P=0.008). In control 2 group, the overlap rate of 2.60% (0.13%，13.69%) was significantly lower than control 1 group (P=0.001). There was no difference between case group and control 2 group. After pairwise comparison between the three groups, the frequency of clonotype TRBV7-2/TRBD1/TRBJ2-1 in case group was higher than that of control 1 group (P=0.029), the frequency of TRBV7-3/TRBD1/TRBJ2-7 in case group was lower than that of control 1 group (P=0.031). The difference of TRBV5-8 was significant in comparing case group with control 1 group (P=0.047). There were 14 clonotypes which had differences between case group and control 2 group in frequency. TRBV28was significant in comparing case group with control 2 group (P=0.028). For diversity, there was no difference among the three groups. Conclusion Clonotype TRBV7-2/TRBD1/TRBJ2-1, TRBV7-3/TRBD1/TRBJ2-7 and TRBV5-8 were associated with coexistence of HBsAg and HBsAb, but the diversity was not associated with TCR β chain CDR3.

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.

Objective: To evaluate the clinical application effects of an iliac-crest-preserving iliac wing bone graft harvesting technique and the bone regenerative ability of the donor site after harvesting. Methods: From January 2016 to June 2017, a series of 39 patients including 28 men and 11 women aged between 16 and 59 y (35±13 y in average) were prospectively collected to treat bone defects using the iliac-crest-preserving iliac wing bone graft harvesting technique. The patient cohort included 38 ipsilateral and 1 bilateral bone harvests taken from 15 femoral fracture non-unions, 8 tibial fracture non-unions, 11 femoral head necroses (hip preserving surgery), 1 tuberculosis deriving hip arthritis with bone defect (total hip arthroplasty), 2 hip prosthesis loosenings (revision), and 2 proximal femoral benign tumors. All patients were treated through comprehensive surgeries containing autologous iliac bone grafting. The surgical time, blood loss, bone graft volume, 24 h post-operative visual analogue scale (VSA) at the iliac surgical site, complications, and bone regeneration of the donor site were documented and evaluated. Results: In the 39 patients (40 sides), the average surgical time was 25±4 min, average blood loss was 79±23 ml, average bone graft volume was 27±6 cm³. The average 24 h post-operative VAS at the iliac surgical site was 1.8±0.7 points. The VSA at the 6 week later and thereafter were 0 in all patients. The iliac incisions in 38 patients (39 sides) were healed uneventfully. However, seroma at the iliac surgical site emerged in 1 patient at the 6th post-operative day in the manner of serous exudation and was treated successfully with non-operative measures. None infections and lateral femoral cutaneous nerve injuries took place. Iatrogenic non-displaced iliac crest fractures happened in the very first 2 patients when taking the crest as a pivot to pry up the graft, which united without special cure at the 3 month post-operative. This complication was completely avoided when shifting the pivot to the anterior pillar containing the anterior iliac spines. None pelvic fractures and heterotopic ossifications took place. Post-operative radiographical examinations revealed that the bone defects at the donor site shrank through bone regeneration, that mamillary or canine-tooth-shaped bone formation occurred in some of the cases, and that none complete bone regeneration took place to eliminate the bone defect at the donor. There were 12 patients in whom pre- and post-operative computed tomographic scans necessitated by the disease were prescribed, which facilitated the measuring of the bone defect at the donor site. The measurement of 13 sides revealed that the bone defects were decreased more or less: the average immediate post-operative bone defect was 25.7±6.5 cm², the average 12 month post-operative bone defect was 12.7±5.3 cm². Conclusion The iliac wing bone graft harvesting technique suggested here is safe and less invasive, in the premise of preserving the iliac crest and retaining the figure of the surgical site, it can harvest a large amount of iliac wing bone graft and reserve the bone regenerative ability of the donor site

Objective Investigate the effect of neonatal hyperbilirubinemia on the detection of HBsAg by chemiluminescence and its elimination methods.Methods Case control study.The HBsAg in human serum was detected in 200 cases of hyperbilirubinemia neonates who were hospitalized in Beijing Children's Hospital,Capital Medical University from July 2015 to May 2016 and whose serum total bilirubin level exceeded 200 μmol/L.The positive serum was further detected by 16 200×g high-spoed centrifugation or blue light irradiation for 8 hours,and the results of re-assay of HBsAg were recorded.The retest positive serum wastested for HBV DNA load and checked the results of their mother's examination in HBV.136 adult serum samples with total bilirubin levels exceeding 200 μmol/L in the Peking University First Hospital,were taken as reference to compare the influence of hyperbilirubinemia between adults and newborns on the determination of HBsAg.Results The median level of serum total bilirubin in neonates was 259.0 μ mol/L (226.5,312.5);median level of indirect bilirubin 244.1 μmol / L(212.5,295.8).Median level of serum total bilirubin in adults 356.4 μmol/L(295.9,435.1);median level ofindirect bilirubin 137.1 μmol/L (107.8,172.7).The HBsAg test was negative in adults,11 cases (5.5％) were positive in newborns,their" HBV DNA load was less than＜100 IU/ml.Among them,9 have inoculated hepatitis B vaccine and 2 were unknown.10 of 11 mothers of infants were healthy and 1 was positive for HBsAg,HBeAb,HBcAb.2 of the 11 positive specimens turned negative of HBsAg after high-speed centrifugation.In addition to high speed centrifugation,4 cases turned negative after blue light irradiation.5 cases remained positive after high speed centrifugation and blue light irradiation.Conclusions Neonatal hyperbilirubinemia,which is different from that of adults,is mainly caused by indirectly bilirubin increased,which is one of the main reasons for false positive detection of HBsAg by chemiluminescence in neonates.High-speed centrifugation and blue light irradiation can eliminate the influence of serum indirect bilirubin on the detection of HBsAg to the greatest extent.

Objective To study the values of clinicopathological features and expression of thyroid transcription factor 1 (TTF-1) in predicting the mutation status of epidermal growth factor receptor (EGFR) gene in patients with non-small cell lung cancer (NSCLC). Methods Mutation status of exons 18, 19, 20 and 21 in EGFR, and expression of TTF-1 protein in 283 cases of NSCLC diagnosed in Shanxi Provincial Cancer Hospital from January 2013 to December 2014 were analyzed by using amplification refractory mutation system (ARMS) and immunohistochemical method. The correlation of EGFR mutations with the clinicopathological features and TTF-1 expression were studied to explore the values of them in the prediction of EGFR mutations. Results Among 283 cases of NSCLC, the rate of EGFR gene mutation was 30.0 ％(85/283), including 3 cases with double mutations(exon 18 and exon 20 double mutations in one case, exon 19 and exon 21 double mutations in one case, exon 20 and exon 21 double mutations in one case). The EGFR gene mutations were associated with gender, histological type, history of smoking, and expression of TTF-1 (all P<0.001), but not related to age and tumor location (P= 0.785, P= 0.138). The combination of factors with high mutation rates (women, adenocarcinoma, no smoking, and TTF-1 positive) made the positive predictive value of EGFR mutations up to 57.6 ％. And the combination of factors with low mutation rates (male, nonadenocarcinoma, smoking history, TTF-1 negative) made the EGFR negative predictive value up to 90.3％. Conclusion The combination of clinicopathological features and TTF-1 expression status in patients with NSCLC has a great predictive value for EGFR mutations, which can provide a useful reference for clinical treatment decision-making.

Objective To investigate the expressions of carbohydrate antigen 19-9(CA19-9), carbohydrate antigen 15-3(CA15-3) and carbohydrate antigen 125(CA125) and their clinical significance in papillary thyroid carcinoma (PTC). Methods The expressions of CA19-9, CA15-3 and CA125 were detected by immunohistochemical MaxVision method in 80 cases of PTC and 80 cases of benign thyroid lesions (BTL), including 34 cases of nodular goiter, 26 cases of Hashimoto's thyroiditis and 20 cases of follicular adenoma. The relationship between expressions of CA19-9, CA15-3 and CA125 and the clinical pathological characteristics were analyzed. Results The expression rates of CA19-9, CA15-3 and CA125 in 80 cases of PTC were 85%, 100%and 43.8%respectively, compared with BTL, the difference was statistically significant (P < 0.01). There was no significant correlation between expressions of CA19-9, CA15-3 and CA125 and age, gender, number and diameter of tumor nodules, lymph node metastasis, and TNM staging (P > 0.05). The sensitivity of CA19-9, CA15-3 and CA125 in the differential diagnosis of PTC and BTL were 85%, 100% and 43.8% respectively, and the specificity were 91.3%, 36.3%and 91.3%, respectively. Conclusion The expressions of CA19-9, CA153 and CA125 are helpful for the differential diagnosis of PTC and BTL.

Objective To analyze the anatomic factors of the central retinal artery occlusion or the ophthalmic artery occlusion after the injection of facial cosmetic surgery.Methods Retrospectively analyzed 3 patients who occurred severely ocular complications just after facial cosmetic injection in last 2 years.The diagnosis of central retinal artery occlusion was confirmed by fundus examination and fundus fluoresce-in angiography.Analysis the blood vessel distribution of the injection site and characteristics of peri-orbit vascular anastomosis.Results All the 3 cases presented no light perception,with eye pain or (and)the eyeball pain.The fundus test and fundus fluorescein angiographies showed central retinal artery obstruction.Facial cosmetic injection pressure significantly exceeded the ophthalmic artery systolic pressure 2 seconds after injection (P <0.05).Dorsal nasal artery and angular artery were anastomotic,and the angular artery was usually anastomotic with lateral nasal branches of the posterior ciliary artery.The filler can enter the ophthalmic artery by the branches of the anastomosis,which can make ophthalmic artery occlusion,central retinal artery occlusion or get occlusion of their branches.Conclusion The injectant may get into the orbital artery and retrograde to the ophthalmic artery,which resulting in ophthalmic artery occlusion,or get into central retinal artery and posterior ciliary artery,which resulting in serious ocular complications.

Objective To investigate the spontaneous neoplastic lesions and their incidences in rats .Methods Sixty male and 60 female specific pathogen-free Wistar rats (4-weeks old ) were used in this study .The rats were acclima-ted for 1 week prior to initiation of the experiment .They were fed with conventional feed for 104 weeks and then sacrificed for histopathological examination .Results Various neoplastic lesions of the rats and their incidences were analyzed and reported.For male rats, their total tumor incidence was 49.12%, the benign tumor incidence was 38.60%and the malig-nant tumor incidence was 17.54%.The benign neoplastic lesions mainly were pituitary adenoma ( 19.30%) , testis Leydig cell tumor (5.26%) and subcutaneous fibroma (5.26%).The malignant neoplastic lesions mainly were squamous cell carcinoma (7.02%) and lymphoid hematopoietic system tumors (3.51%).For female rats, their total tumor inci-dence was 60.34%, the benign tumor incidence was 50.00%and the malignant tumor incidence was 15.52%.The benign neoplastic lesions mainly were breast fibroadenoma (25.86%) and pituitary adenoma (24.14%).The malignant neoplas-tic lesions mainly were adenocarcinoma (5.17%) and breast cancer (3.45%).Conclusions The spontaneous neoplastic lesions and their incidences reported in this paper provide another data of the spontaneous tumors of SPF Wistar rats and may provide some reference for relevant technical staffs .