Complete androgen insensitivity syndrome: a case report and literature review.

Complete androgen insensitivity syndrome (CAIS) is a rare disease that can be easily misdiagnosed. Before puberty, this condition is easily misdiagnosed as an inguinal hernia. This case report describes a 31-year-old phenotypically female patient with CAIS who was misdiagnosed twice previously with an inguinal hernia. Her karyotype analysis showed that she was 46, XY. She underwent a bilateral gonadectomy and long-term hormone replacement therapy. A Leydig cell tumour of the right testis was diagnosed postoperatively. This report also reviews the current understanding of the diagnosis and treatment of CAIS.

[Imaging characteristic of Stafne bone cavity：a retrospective study based on cone-beam CT].

PURPOSE: To guide clinical decision-making more efficiently via collecting and analyzing the imaging data of patients with Stafne bone cavity(SBC). METHODS: Six patients with SBC were retrospectively reviewed in Stomatological Hospital of Shandong University. By assessing cone-beam CT (CBCT) data, age, sex, complaint, cavity location, diameter at three dimension, maximal cross-sectional area of multi-planar reconstruction planes, content gray scale, morphological classification and its relationship with mandibular canal were recorded respectively. RESULTS: A total of 6 cases were inadvertently found on CBCT, with no symptoms. The locations of SBC were between mandibular molar region and mandibular angle, inferior border of mandible and mandibular canal, mostly at lingual side. Three were on the left and three were on the right. The bone cavity was elliptic and its long axis was consistent with the long axis of the mandible, with an average long axis diameter of (16.43±4.54) mm, horizontal axis diameter of (6.91±1.48) mm, vertical axis diameter of (10.24±2.10) mm. According to the multi-planar reconstruction planes readings, the maximal cross-sectional area of the bone cavity was (91.93±25.52) mm2, the maximal coronal area was (57.26±23.23) mm2, and the maximal sagittal area was (127.80±51.22) mm2. In view of the classification in the relationship between SBC marginal line and buccal cortical bone, there were 2 cases of type I cavity, 3 cases of type II cavity and 1 case of type III cavity. The connection between the bone cavity and the surrounding anatomical structure was classified into 3 conditions: covering penetration, adjacency and separation on the basis of the relative position between the cavity boundary with the mandibular inferior margin and the mandibular canal in sagittal plane. In addition, the content type could be primarily identified depending on estimation of corrected grey scale in the center of bone cavity. CONCLUSIONS: CBCT can make an intuitive and clear diagnosis of Stafne bone cavity, which brings great significance into the early clinical decision-making, thus not only avoiding unnecessary surgery, reducing the waste of additional medical resources, but also decreasing the physical and mental trauma of patients.

Exciting Performance of Plasma Fibrinogen in Periprosthetic Joint Infection Diagnosis.

OBJECTIVE: To test the significance of serum C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), the platelet count/mean platelet volume ratio (PC/MPV), plasma fibrinogen, and D-Dimer in periprosthetic joint infection (PJI) diagnosis. METHODS: We retrospectively analyzed the clinical data of 149 patients diagnosed from July 2016 to December 2019 with primary osteoarthritis (OA group, average age 63.18 years [range, 53-82 years] 18 males, 46 females), PJI (PJI group, average age 63.74 years [range, 52-81 years], 16 males, 31 females), and aseptic loosening (aseptic group, average age 63.18 years [range, 53-80 years], 12 male, 26 female) in our department. Demographic data and the sensitivity and specificity of preoperative CRP, ESR, PC/MPV, fibrinogen, and D-Dimer in PJI diagnosis were compared. RESULTS: There were no significant differences when the demographic data of the three groups were compared. The expression level of CRP (50.67 ± 58.98 mg/L), ESR (50.55 ± 25.81 mm/h), PC/MPV (35.79 ± 18.00), and fibrinogen (4.85 ± 1.33 µg/mL) in the PJI group were higher than in the OA group (CRP: 4.09 ± 9.68 mg/L; ESR:13.44 ± 9.32 mm/1 h; PC/MPV: 24.97 ± 7.58; fibrinogen: 3.09 ± 0.55 µg/mL) and the aseptic group (CRP: 7.01 ± 11.83 mg/L; ESR: 22.47 ± 17.53 mm/1 h; PC/MPV: 25.18 ± 11.48; fibrinogen: 3.39 ± 0.80 µg/mL), respectively. The expression level of plasma D-dimer (1.60 ± 1.29 mg/L) in the PJI group was higher than in the OA group (0.49 ± 0.42 mg/L) but similar to that in the aseptic group (1.21 ± 1.35 mg/L). Receiver operating characteristic (ROC) curve analysis demonstrated that the areas under the ROC curve (AUC) for CRP, ESR, PC/MPV, fibrinogen, and D-dimer were 0.892 (95% confidence interval, 0.829-0.954), 0.888 (0.829-0.947), 0.686 (0.589-0.784), 0.873 (0.803-0.943), and 0.835 (0.772-0.899), respectively. When PC/MPV > 31.70, fibrinogen >4.01 µg/mL, and D-dimer >1.17 mg/L were set as the threshold values for the diagnosis of PJI, the sensitivity of PC/MPV in PJI diagnosis was lower than that of ESR and plasma fibrinogen. In contrast, there was no significant difference when comparing the specificity of CRP, ESR, PC/MPV, fibrinogen, and D-dimer in PJI diagnosis. CONCLUSION: Plasma fibrinogen is a good new auxiliary diagnostic marker for PJI.

Identification of aberrantly methylated differentially expressed genes targeted by differentially expressed miRNA in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary bone tumors diagnosed in children and adolescents. Recent studies have shown a prognostic role of DNA methylation in various cancers, including OS. The aim of this study was to identify the aberrantly methylated genes that are prognostically relevant in OS. METHODS: The differentially expressed mRNAs, miRNAs and methylated genes (DEGs, DEMs and DMGs respectively) were screened from various GEO databases, and the potential target genes of the DEMs were predicted by the RNA22 program. The protein-protein interaction (PPI) networks were constructed using the STRING database and visualized by Cytoscape software. The functional enrichment and survival analyses of the screened genes was performed using the R software. RESULTS: Forty-seven downregulated hypermethylated genes and three upregulated hypomethylated genes were identified that were enriched in cell activation, migration and proliferation functions, and were involved in cancer-related pathways like JAK-STAT and PI3K-AKT. Eight downregulated hypermethylated tumor suppressor genes (TSGs) were identified among the screened genes based on the TSGene database. These hub genes are likely involved in OS genesis, progression and metastasis, and are potential prognostic biomarkers and therapeutic targets. CONCLUSIONS: TSGs including PYCARD, STAT5A, CXCL12 and CXCL14 were aberrantly methylated in OS, and are potential prognostic biomarkers and therapeutic targets. Our findings provide new insights into the role of methylation in OS progression.

NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma.

Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro, NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction. Cisplatin could activate PI3K-Akt-mTOR pathway activity in early times, whereas, NVP-BEZ235 could inhibit PI3K-Akt -mTOR pathway activity all the times alone or combined with cisplatin. What's more, NVP-BEZ235 could switch function of autophagy induced by cisplatin to synergize cisplatin sensitivity. In vivo, pronounced decrease in tumor cell proliferation and increase in apoptosisin combination-treated mouse xenograft models compared with cisplatin or NVP-BEZ235 treated models. All these results suggest NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS.

MX1013, a dipeptide caspase inhibitor with potent in vivo antiapoptotic activity.

1. Caspases play a critical role in apoptosis, and are considered to be key targets for the design of cytoprotective drugs. As part of our antiapoptotic drug-discovery effort, we have synthesized and characterized Z-VD-fmk, MX1013, as a potent, irreversible dipeptide caspase inhibitor. 2. MX1013 inhibits caspases 1, 3, 6, 7, 8, and 9, with IC50 values ranging from 5 to 20 nm. MX1013 is selective for caspases, and is a poor inhibitor of noncaspase proteases, such as cathepsin B, calpain I, or Factor Xa (IC50 values >10 microm). 3. In several cell culture models of apoptosis, including caspase 3 processing, PARP cleavage, and DNA fragmentation, MX1013 is more active than tetrapeptide- and tripeptide-based caspase inhibitors, and blocked apoptosis at concentrations as low as 0.5 microm. 4. MX1013 is more aqueous soluble than tripeptide-based caspase inhibitors such as Z-VAD-fmk. 5. At a dose of 1 mg kg-1 i.v., MX1013 prevented liver damage and the lethality caused by Fas death receptor activation in the anti-Fas mouse-liver apoptosis model, a widely used model of liver failure. 6. At a dose of 20 mg kg-1 (i.v. bolus) followed by i.v. infusion for 6 or 12 h, MX1013 reduced cortical damage by approximately 50% in a model of brain ischemia/reperfusion injury. 7. At a dose of 20 mg kg-1 (i.v. bolus) followed by i.v. infusion for 12 h, MX1013 reduced heart damage by approximately 50% in a model of acute myocardial infarction. 8. Based on these studies, we conclude that MX1013, a dipeptide pan-caspase inhibitor, has a good combination of in vitro and in vivo properties. It has the ability to protect cells from a variety of apoptotic insults, and is systemically active in three animal models of apoptosis, including brain ischemia.