Repair of buccal mucosa and floor of mouth defects using keystone design perforator island flap.

OBJECTIVE: To assess the feasibility of utilizing the keystone design perforator island flap (KDPIF) for the repair of small to medium-sized defects in the buccal mucosa and floor of mouth (cT1-2 stage tumor). STUDY DESIGN: We conducted a retrospective analysis of eight patients who underwent KDPIF to address oral defects at the Affiliated Hospital of Qingdao University between June 2021 and September 2022. Patient information, including medical history, defect site, flap size, operative time, hospital stay, complications, and postoperative recovery of oral function, was comprehensively evaluated. RESULTS: Eight patients (6 females and 2 males) underwent reconstruction using KDPIF. The mean operation time was 58.5 minutes (55-63 minutes), with an average length of stay of 3.5 days (3-5 days). None of the 8 cases (100%) exhibited flap splitting necrosis or infection. Moreover, no scar contracture was observed, and oral functions, including the degree of opening, type of opening, tongue mobility, speech function, and swallowing function, were successfully restored. One patient (12.5%) experienced bleeding from the incision on the first postoperative day, but following compression, hemostasis was achieved, and the incision healed well. CONCLUSIONS: KDPIF demonstrates technical feasibility and suitability for repairing small to medium-sized buccal mucosa and floor of mouth defects (cT1-2).

Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption.

Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40µM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine.

Development of a supercritical fluid chromatography-tandem mass spectrometry method for the determination of azacitidine in rat plasma and its application to a bioavailability study.

Azacitidine is widely used for the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukaemia (AML). The analysis of azacitidine in biological samples is subject to interference by endogenous compounds. Previously reported high-performance liquid chromatography/tandem mass spectrometric (HPLC-MS/MS) bioanalytical assays for azacitidine suffer from expensive sample preparation procedures or from long separation times to achieve the required selectivity. Herein, supercritical fluid chromatography with tandem mass spectrometry (SFC-MS/MS) was explored as a more promising technique for the selective analysis of structure-like or chiral drugs in biological matrices. In this study, a simple, rapid and specific SFC/MS/MS analytical method was developed for the determination of azacitidine levels in rat plasma. Azacitidine was completely separated from the endogenous compounds on an ACQUITY UPLC™ BEH C18 column (100 mm×3.0 mm, 1.7 µm; Waters Corp., Milford, MA, USA) using isocratic elution with CO2/methanol as the mobile phase. The single-run analysis time was as short as 3.5 min. The sample preparation for protein removal was accomplished using a simple methanol precipitation method. The lower limit of quantification (LLOQ) of azacitidine was 20 ng/mL. The intra-day and inter-day precisions were less than 15%, and the relative error (RE) was within ±15% for the medium- and high-concentration quality control (QC) samples and within ±20% for the low-concentration QC samples. Finally, the developed method was successfully applied to a pharmacokinetic study in rats following the intravenous administration of azacitidine.

Iron(III)-catalyzed cyclization of alkynyl aldehyde acetals: experimental and computational studies.

FeCl(3)6 H(2)O- and FeBr(3)-catalyzed Prins cyclization/halogenation of alkynyl aldehyde acetals has been realized with acetyl chloride or bromide as halogen source in dichloromethane to afford 2-(1-halobenzylidene or alkylidene)-substituted five-membered carbo- and heterocycles, and thus provides an alternative route for vinylic C-Cl and C-Br bond formation. Five- to eight-membered cyclic enones were efficiently synthesized by FeCl(3)6.H(2)O-catalyzed intramolecular cyclization of alkynyl aldehyde acetals in acetone under mild conditions. An oxocarbonium species generated in situ is proposed to initiate the reaction, and the target products are formed via vinylogous carbenium cation and oxete intermediates according to DFT calculations. Intermolecular reactions of alkynes and aldehyde acetals were also investigated with 20-40 mol% FeCl(3)6.H(2)O catalyst, and produced alpha,beta-unsaturated enones and chlorinated indene derivatives. The present protocol has applications in the synthesis of carbo-, oxa- and azacycles.