First Family Case of Hemoglobinopathy Titusville in China with Falsely Low SpO2 and Unmeasurable SaO2.

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.

N6-methyladenosine demethylase FTO related to hyperandrogenism in PCOS via AKT pathway.

BACKGROUND: Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and obesity-associated protein (FTO), a m6A demethylase, is abnormal in the occurrence of ovarian diseases. However, the mechanism of FTO in the pathogenesis of PCOS is still unclear. METHODS: The level of FTO in clinical samples, PCOS rat with hyperandrogenism and granulosa cells (GCs) lines effected by DHT were investigated by ELISA, qRT-PCR, WB, and IHC, while m6A RNA methylation level was studied by m6A Colorimetric and androgen level was tested through ELISA. Changes in steroid hormone synthetase and androgen receptor (AR)/prostate-specific antigen (PSA) levels in vitro were visualized by WB after transient transfection silenced FTO. The effect of DHT combined with FTO inhibitor meclofenamic acid (MA) on FTO, AR/PSA, and AKT phosphorylation were also demonstrated by WB. The co-localization of FTO and AR in KGN cells was analyzed by confocal microscopy, and the physiological interaction between FTO and AR was studied by Co-IP assay. The effect of FTO-specific inhibitor MA, AKT phosphorylation inhibitor LY294002, and the combined them on GCs proliferation and cell cycle were evaluated by drug combination index, EDU assay, and flow cytometry analysis. RESULTS: FTO expression was upregulated in follicular fluid and GCs in PCOS patients clinically. The high FTO expression in patients was negative with the level of m6A, but positive with the level of androgen. The upregulation of FTO was accompanied with a decrease in the level of m6A in PCOS rat with hyperandrogenism. Dihydrotestosterone (DHT) promoted the FTO expression and inhibited m6A content as a dose-dependent way in vitro. In contrast, suppression of FTO with siRNA attenuated the expression of steroid hormone synthetase such as CYP11A1, CYP17A1, HSD11B1, HSD3B2 except CYP19A1 synthetase, ultimately inducing the decrease of androgen level. Suppression of FTO also decreased the biological activity of androgen through downregulation AR/PSA. MA treatment as the specific FTO antagonist decreased cell survival in time- and dose-dependent way in GCs lines. Correspondingly, MA treatment decreased the expression of FTO, AR/PSA expression, and AKT phosphorylation in the presence of DHT stimulation. Additionally, we also speculate there is a potential relation between FTO and AR according to FTO was co-localized and interacted with AR in KGN cells. Compared with AKT phosphorylation inhibitor LY294002 or MA alone, LY294002 combined with MA synergistically inhibited cell survival and increased G2/M phase arrest in GC line. CONCLUSIONS: We first evaluated the correlation of FTO and m6A in PCOS clinically, and further explored the mechanism between FTO and hyperandrogenism in PCOS animal and cell models. These findings contributed the potential therapy by targeting the FTO for hyperandrogenism in PCOS.

Systematic analysis of expression profiles and prognostic significance of the FGF gene family in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with one of the highest associated mortality rates worldwide, and a 5-year survival rate of <5%. Fibroblast growth factors (FGFs) serve important roles in numerous cellular functions, and dysregulation of FGFs contributes to various cancer types. However, there are few reports on the function of FGFs in PAAD. The Assistant for Clinical Bioinformatics database, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter and Tumor Immune Estimation Resource were utilized to perform the protein-protein interaction network, functional enrichment, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox, differential expression, prognostic value and immune cell infiltration analyses of FGFs in patients with PAAD. Immunohistochemistry (IHC) was used to verify the predictive value of the model. A total of 22 FGF genes were identified. Based on the results of LASSO Cox regression analysis, a total of six genes, including FGF2, FGF8, FGF9, FGF13, FGF17 and FGF22, were selected for the establishment of the prognostic gene signature. High transcriptional levels of FGF17 and FGF22 were significantly associated with long overall survival. The expression of FGFs was associated with the infiltration of various immune cells. According to univariate and multivariate analyses, FGF2 and FGF8 may be useful independent prognostic biomarkers for the prognosis of patients with PAAD. IHC demonstrated that FGF2 and FGF8 were more highly expressed in PAAD tissues compared with that in normal tissues. The present findings offer a novel understanding for the selection of FGF prognostic biomarkers in PAAD.

[Effect of strontium ranelate on chondrogenic differentiation of rat bone mesenchymal stem cells].

PURPOSE: The aim of present study was to explore the effect of strontium ranelate (SrR) on the proliferation and chondrogenic differentiation of rat bone mesenchymal stem cells (BMSCs). METHODS: Rat BMSCs were isolated and cultured in chondrogenic differentiation medium containing 0.25-2.0 mmol/L strontium ranelate. CCK-8 assay was used to study the influence of cell proliferation. Toluidine blue staining and alizarin blue staining were used to observe chondrogenic differentiation. Quantitative hydroxyproline (Hyp) activity assay was conducted. PCR and Western blots were used to detect the expression of related genes and proteins. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: 0.25 mmol/L strontium ranelate did not inhibit the proliferation of BMSCs and promote the expression of chondroitin sulfate and proteoglycan. Hyp assay showed a higher content of collagen fibers in extracellular matrix in 0.25 mmol/L SrR treatment group. PCR and WB also showed up-regulated expression of Sox-9, Col-Ⅱ gene and protein, Aggrecan protein, and suppressed expression of MMP-9 gene. CONCLUSIONS: 0.25 mmol/L SrR could significantly promote chondrogenic differentiation of BMSCs.

[Effect of ball attachments with different materials on retention of mandibular implant supported overdenture].

PURPOSE: To investigate the effect of ball attachments with different materials on retention of mandibular implant supported overdenture. METHODS: The experimental groups were divided into group A (titanium ball / titanium cap group) and group B (titanium ball / golden cap group), each group had 3 samples. A standard mandibular edentulous model was made, and the implants (4.8*10 RN SP) were embedded in the bilateral canine region. Mandibular complete dentures were made routinely and the attachments were attached. Five thousand times of insertion-separation cycles were carried out. After 200 times of cycles, the retention force was tested. The difference between 2 groups was compared by using SPSS 13.0 software package. The change of positive structure surface morphology was observed under scanning electron microscope at the beginning and the end of the experiment. RESULTS: The retention force of group A decreased from （27.00±0.16） N to （4.18±0.03） N, and the retention force of group B decreased from （21.58±0.06） N to （19.15±0.06）N. Decay of retention of group A was significantly greater than that of group B. At the end of the experiment, the globular structure of group A was severely broken, while a smooth and clear spherical structure was displayed in group B. CONCLUSIONS: The retention of mandibular implant supported overdenture decreases with the increase of insertion-separation times. The decay of retention force is related to destruction of positive structure surface. The fatigue resistance of the precious metal material is better.