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Translational Medicine. All rights reserved.Background Tapered femoral stems have become popular in revision total hip arthroplasty (rTHA). Increasing the distal taper angle may mitigate subsidence. This study reports osseointegration of a new 3 degree distal taper revision stem at minimum 4 years post-operatively. Methods Indication for surgery, pre-operative bony deficiency and latest clinical, tribological and radiological follow-up were analysed. Radiographs were assessed by two blinded observers for preoperative femoral bone stock according to Paprosky, postoperative subsidence according to Callaghan and restoration of femoral bone stock over time according to Kolstad. Stem integration was determined using the Rodriguez classification. Results Twenty-three cases were analyzed at 5.9±1.0 years. All patients presented with Paprosky III defects. All stems met the criteria for osseointegration. Spot welds occurred distal to the proximal modular junction and at the tip. Two femora with severe proximal femoral bone loss recovered bone stock by final follow-up but two demonstrated stress shielding. No intraoperative fractures occurred. One stem subsided early but remained stable and osseointegrated at final follow up. There were no stem failures due to taper corrosion or modular junctional failure. Conclusions This study reports good osseointegration and low subsidence with a novel fluted, 3-degree tapered femoral stem demonstrates at medium-term follow-up in cases with severe femoral bone deficiency. 2019 Annals of Translational Medicine. All rights reserved.Background The purpose of this study was to investigate the incidence of venous thromboembolism (VTE) in epidermal growth factor receptor (EGFR) mutations patients with lung adenocarcinoma, to provide clinical basis for the perioperative prevention and treatment of VTE in patients with lung cancer. Methods This study included patients with invasive lung adenocarcinoma confirmed by pathology from July 2016 to March 2018 after surgical pulmonectomy in Thoracic Surgery Department of Beijing Chaoyang Hospital. All enrolled patients were tested for relevant gene mutations. All patients were classified as adenocarcinoma subtypes by the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). Patients were divided into the VTE group and the control group according to whether VTE occurred postoperatively. Baseline data, gene test results, operative data and tumor pathology data between the two groups were compared. Results According tng adenocarcinoma, acinar dominant lung adenocarcinoma, FEV1 and difference of D-dimer (d1-pre) are independent risk factors for postoperative lung cancer complicated with VTE. Conclusions The incidence of VTE was 10.2% in patients with invasive lung adenocarcinoma without prophylactic anticoagulant therapy. EGFR gene mutation is an independent risk factor for postoperative VTE in lung cancer, and the incidence of VTE in adenocarcinoma with alveolar predominance is the highest. Other independent risk factors included the difference of D-dimer (d1-pre) and preoperative FEV1. 2019 Annals of Translational Medicine. All rights reserved.Background Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear. Methods In silico analysis of the expression of GD3s in TNBC was conducted using The Cancer Genome Atlas (TCGA) and Oncomine databases. The proliferation of breast cancer cells was measured by MTT assay, colony formation by the soft agar method, and migration and invasion using Boyden chamber inserts. The methylation level of the gene encoding GD3s, ST8SIA1, in specimens was assessed by qMS-PCR and in silico using the UCSC gene browser. Protein expression was examined via immunohistochemistry (IHC), qRT-PCR and Western immunoblotting. Results In silico analysis showed a higher GD3s expression in ER- than ER+ breast cancers and GD3s was also highly expressed in TNBC compared to other types of breast cancers. The elevated GD3s expression in TNBC cells and tissues was associated with hypomethylation of the ST8SIA1 gene. Overexpression of GD3s in human breast cancer cells increased their proliferation, migration, invasion and colony formation ability. GD3s expression in breast cancers was closely associated with relapse-free survival (RFS) and overall survival (OS). Conclusions In summary, these results suggest that GD3s may be a potential biomarker and drug target in treatment of TNBC. 2019 Annals of Translational Medicine. All rights reserved.Background Our study aimed to reveal the relationship of maternal pentraxin 3 (PTX3)'s serum concentrations in early pregnancy with gestational diabetes mellitus (GDM) and to explore its potential in the prediction of GDM. Methods Totally 824 pregnant women were enrolled and divided into a GDM group and a normal glucose tolerance (NGT) group, whose maternal fasting serum PTX3 levels, plasma glucose and insulin were collected. The beta cell function index and quantitative insulin sensitivity check index (QUICKI) was calculated and a homeostatic model assessment of insulin resistance (HOMA-IR) was used with SPSS 22 software used for statistical analysis. Results Of all subjects, 13.59% developed GDM. Compared to the NGT group, the PTX3 level was increased in the GDM group (1.48 vs. 1.52 ng/mL, P less then 0.05), and independently associated with the prediction of GDM (4.209, 95% CI, 1.756-10.091) (P=0.001). The area under receiver operating characteristic curve (AUROC) of the combined screening of PTX3 for GDM was incremented to 0.657 by the addition of maternal characteristics, and it reached a maximum of 0.743 in further combination with biochemical markers. Conclusions Serum PTX3 levels in early pregnancy may provide a useful approach for early prediction of GDM. 2019 Annals of Translational Medicine. Roxadustat All rights reserved.Background Reduced folate carrier 1 (RFC1) gene is a candidate for susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P). Association between RFC1 A80G polymorphism and NSCL/P have been studied. The published results are conflicting. Methods A meta-analysis of the association between RFC1 A80G polymorphism and NSCL/P was carried out using Stata13.0. A systematic literature search was performed through the PubMed, EMBASE, the Cochrane Library, Web of Science, ScienceDirect, EBSCOhost, China Biology Medicine databases, China National Knowledge Infrastructure and the Wanfang databases. All relevant studies up to 9 September 2019 were identified. Results Nine case-control studies including 4,229 total participants (1,334 NSCL/P children, 1,515 healthy children, 656 mothers of the NSCL/P children, and 724 mothers of healthy control children) were included in this study. The meta-analysis revealed that two genetic models of RFC1 A80G polymorphism in NSCL/P children increased risk of NSCL/P the homozygote model (GG vs. AA, OR =2.346, 95% CI 1.127-4.884) and the recessive model (GG vs. AG + AA, OR =1.503, 95% CI 1.049-2.152). Further sensitivity analysis indicated that the frequency of G allele and GG genotype in NSCL/P children was significantly higher than those in the control. However, there was no significant statistical differences after Bonferroni correction. Subgroup analyses indicated the presence of the association of all the model with NSCL/P risk in the Indian children. RFC1 A80G polymorphism in the maternal population of NSCL/P children was not significantly associated with children NSCL/P. Conclusions The RFC1 A80G polymorphism was a candidate for susceptibility to NSCL/P in the Indian pediatric population. More studies with larger samples are necessary to reach more conclusive outcomes. 2019 Annals of Translational Medicine. All rights reserved.Background Renal anemia is a severe complication of chronic kidney disease (CKD) and may worsen its prognosis. Roxadustat is the only oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has been proved effective to treat renal anemia. However, effects of roxadustat on non-dialysis-dependent CKD (NDD-CKD) have yet to be supported by evidence-based medicine. Methods Based on the databases of PubMed, EMBASE and Web of Science by 12 April 2019 (CRD42019133225), a meta-analysis of randomized controlled trials (RCTs) on roxadustat for treatment of NDD-CKD was conducted. Primary outcomes were parameters of hemoglobin (Hb) and Hb response. Secondary outcomes were hepcidin, ferritin, total iron binding capacity (TIBC), transferrin saturation (TAST), incidences of diarrhea, adverse events (AEs) and severe adverse events (SAEs). The risk of bias and the quality of evidence were assessed, respectively. Both continuous and binary variables were analyzed by the random effects models. Sensitivity analyts by improving Hb and iron metabolism. Oral administration of roxadustat was relatively safe in that roxadustat did not increase the incidence of AEs and SAEs. 2019 Annals of Translational Medicine. All rights reserved.Background Endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) is a well-established technique for diagnosing pancreatic malignancy. In general, tissue of pancreatic head and uncinate process lesions is obtained via a transduodenal approach. However, this tissue-acquisition modality is not applicable in cases of pyloric obstruction and duodenal bulb ulceration. The aim of this study is to determine the feasibility and safety of a novel EUS-guided transgastric trans-portal system FNA in the diagnosis of pancreatic head and uncinate process cancer. Methods This study retrospectively analyzed 26 consecutive inpatient patients who had undergone EUS-FNA for highly suspected malignancy of pancreatic head or uncinate process between December 2013 and December 2018. EUS-guided transgastric trans-portal vein (trans-PV, n=2) or trans-superior mesenteric vein (trans-SMV, n=24) FNA was performed in the patients under conscious sedation. Feasibility, diagnostic yield and complication rates of the technique were evaluated. Results Specimens obtained by EUS-guided transgastric trans-portal system FNA were adequate for cytological evaluation in all 26 patients. Cytological diagnosis of adenocarcinoma was established in 22 patients, while the remaining 4 patients were negative. The diagnostic accuracy, sensitivity and specificity were 92.3%, 91.7% and 100% respectively. No immediate or delayed procedure-related complications were observed. Conclusions EUS-guided transgastric trans-portal system FNA is a feasible and probably safe method for diagnosing pancreatic head and uncinate process malignancy. Careful selection of the potential candidates and close periprocedural observation are mandatory. 2019 Annals of Translational Medicine. All rights reserved.

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