Analysis of the expression profile of serum exosomal lncRNA in breast cancer patients.

BACKGROUND: Breast cancer (BC) is a common tumor that seriously affects women's physical/mental health and even life. BC invasion and metastasis are still the main causes of mortality in BC patients. Exosomal long non-coding RNAs (exo-lncRNA) play an important role in cell communication and can help to understand better the physiological and pathological conditions that result from BC. This study investigates new potential targets and functions of the expression profiles of exo-lncRNAs in BC patients through high-throughput screening and bioinformatics. METHODS: Samples were collected from two BC patients and one healthy subject. The serum exosomal RNAs were subsequently purified, and a library was established for quality inspection and sequencing. The resultant data was compared with the reference data to obtain the differential expression of exo-lncRNAs, and predict the target genes. To obtain the final results, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to annotate the function and pathway of the differentially expressed genes. RESULTS: After a comprehensive comparison of the BC patients and healthy subjects, we discovered five up-regulated exo-lncRNAs and six down-regulated exo-lncRNAs of interest. Combining our results with a literature review and screening, we found that VIM-AS1, SNHG8, and ELDR play a role in the progression of BC, with VIM-AS1 predicting 35 target miRNAs; SNHG8 predicting 12 target miRNAs, and ELDR predicting 24 target miRNAs. Target prediction considered that the target gene of VIM-AS1 was VIM and that the target gene of SNHG8 was PRSS12. GO enrichment analysis showed that VIM mainly played a role in cell processes, biological regulation, metabolic regulation, and molecular adhesion, while PRSS12 was enriched through cell metabolism, catalytic activity, and hydrolase activity. KEGG pathway enrichment results also indicated how the VIM protein functions in cancer development through the viral infection signaling pathway and miRNA signaling pathway. CONCLUSIONS: There is a significant difference in the expression profiles of serum exo-lncRNAs between BC patients and healthy individuals. This may be closely related to BC's occurrence, development, and metastasis, and therefore provides a theoretical basis for more in-depth studies into exo-lncRNA.

Determination of benzonatate and its metabolite in human plasma by HPLC-MS/MS: A preliminary pharmacokinetic study in healthy Chinese volunteers after oral administration of benzonatate soft capsule.

Benzonatate has been used as a non-narcotic oral antitussive drug for many years. Its pharmacokinetics has never been reported due to the technical difficulties in detecting benzonatate by mass spectrometry. However, its concentration can be extrapolated based on the concentration of its metabolite, 4-(butylamino)benzoic acid (BBA). In this study, two sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods were developed and fully validated for the determination of the original 4-(butylamino)benzoic acid (method B) and total 4-(butylamino)benzoic acid (containing the original 4-(butylamino)benzoic acid and 4-(butylamino)benzoic acid converted from benzonatate after collection, method A). For both methods, one-step protein precipitation by methanol was performed to extract analytes from the plasma samples. Chromatographic separation was done on an InfinityLab Poroshell 120 Phenyl Hexyl column (2.1 mm × 50 mm, 2.7 µm, Agilent) with initial mobile phase consisting of 5 mM ammonium acetate containing 0.3% formic acid and acetonitrile (60:40, v/v) at a flow rate of 0.3 mL/min. Quantification was achieved by multiple reaction monitoring (MRM) in electron spray ionization (ESI) positive mode with the transitions of m/z 194.2 → 138.1 and 515.3 → 497.3 for 4-(butylamino)benzoic acid and telmisartan (the internal standard), respectively. The two methods exhibited good linearity over the concentration range of 10-10000 ng/mL. Both of the methods were successfully applied to the preliminary pharmacokinetic study in healthy Chinese volunteers after oral administration of benzonatate soft capsule at a single dose of 100 mg. The results showed that 4-(butylamino)benzoic acid and benzonatate were rapidly absorbed and reached a maximum concentration (Cmax) of 1708 ±â€¯457 ng/mL and 1063 ±â€¯460 ng/mL, respectively. The half-life (t1/2) were 1.32 ±â€¯0.29 h for 4-(butylamino)benzoic acid and 1.01 ±â€¯0.41 h for benzonatate. The area under the curve from 0 h to 10 h (AUC0-10) for 4-(butylamino)benzoic acid and benzonatate were 2103 ±â€¯918 ng/mL·h and 1097 ±â€¯559 ng/mL·h, respectively. And the data was valuable for further clinical study.

Determination of fenticonazole in human plasma by HPLC-MS/MS and its application to pharmacokinetic studies.

Two simple and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS), and simple protein precipitation by acetonitrile containing 2% acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2-199.1 for fenticonazole and m/z 430.2-372.3 for mifepristone. The validated linear ranges were 5-1000 pg/mL and 0.1-20 ng/mL fenticonazole in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

Transparotid approach in the treatment of intracapsular condylar fracture.

PURPOSE: Open reduction and internal fixation of intracapsular condylar fractures is a great challenge due to the confined access. This study aims to explore the feasibility of transparotid approach in the treatment of intracapsular condylar fractures. PATIENTS AND METHODS: Eight patients with intracapsular condylar fractures were enrolled in this study. A minimized preauricular incision and transparotid access was used. Blunt dissection was performed perpendicularly to the condyle. The reduction and fixation of intracapsular condylar fractures were performed. After confirming that the fracture was fixed rigidly, the articular disc was repositioned. RESULTS: Using this incision, the condylar head and fracture stump were exposed perpendicularly. No extensive incision was needed and minimal invasion was realized. Postoperative CT scan showed that the condyle had been repositioned and fixed in the normal position. Occlusal disturbance, restriction of mouth opening, and lateral deviation were not found in the follow-up. CONCLUSIONS: Transparotid approach gave an optimal view of the bony field, which allowed surgeons to work perpendicularly to the fracture, and facilitated the reduction of medially displaced proximal stumps. It was regarded as an ideal and valuable alternative in this potentially complicated procedure.

Endoscope-assisted conservative condylectomy combined with orthognathic surgery in the treatment of mandibular condylar osteochondroma.

Mandibular condylar osteochondroma (OC) results in asymmetric prognathism with facial morphologic and functional disturbance. The aim of this study was to explore the feasibility of endoscope-assisted conservative condylectomy combined with simultaneous orthognathic surgery in the treatment of condylar OC. Thirteen patients with OC of the mandibular condyle were enrolled in this study. With the aid of endoscope, condylar OC resection and conservative condylectomy were carried out via intraoral approach. A direct vision of the magnified and illuminated operative field was realized. Simultaneous orthognathic surgery was used to correct facial asymmetry and malocclusion. All patients healed uneventfully. No facial nerve injury and salivary fistula occurred. Facial symmetry and morphology were greatly improved, and stable occlusion was obtained in all cases. The patients showed no signs of recurrence and temporomandibular joint ankylosis in the 16 to 54 months of follow-up. Endoscope-assisted tumor resection and condylectomy combined with simultaneous orthognathic surgery provide us a valuable option in the treatment of mandibular condylar OC.

Piezoelectric decortication applied in periodontally accelerated osteogenic orthodontics.

Our aim was to evaluate the application of piezoelectric decortication in periodontally accelerated osteogenic orthodontics (PAOO). One hundred fifty-six patients with severe skeletal malocclusions were enrolled in this study. Ultrasonic decortications were performed in 187 labial or lingual PAOO of the maxillary and mandibular anterior teeth. Orthodontic decompensation started from the fifth day after operation. All patients healed uneventfully and no severe periodontic complications were recorded. Rapid teeth movement and relatively short treatment duration were realized. Alveolar fenestration and bony dehiscence was successfully addressed. With physical and mechanical properties of absence of macrovibration, ease of use and control, piezosurgery showed its great values in PAOO.