Are contralateral submental artery perforator flaps feasible for the reconstruction of postoperative defects of oral cancer?

BACKGROUND: We evaluated the clinical applications of the reconstruction of postoperative defects of the oral cavity using contralateral submental artery flaps. METHODS: A retrospective study of 18 patients with postoperative intraoral cancer defects reconstructed with contralateral submental artery perforator flaps between October 2018 and October 2019 in our department was conducted. The defect area, flap size, and complications were evaluated. RESULTS: All patients were diagnosed based on pathological examinations: 2 with adenoid cystic carcinoma and 16 with squamous cell carcinoma. The submental artery perforator flap used for simultaneous repair was 8 to 15 cm in length and 4 to 6.5 cm in width. The survival rate of flap reconstruction was 100% with no donor site complications. CONCLUSIONS: Contralateral submental artery flap reconstruction is a suitable alternative for moderate to large intraoral defects, postoperative mouth floor defects, and oral cavity composite defects of oral malignant tumors without contralateral lymph node metastases.

Research Progress of nucleic acid delivery vectors for gene therapy.

Gene therapy has broad prospects as an effective treatment for some cancers and hereditary diseases. However, DNA and siRNA are easily degraded in vivo because of their biological activities as macromolecules, and they need the effective transmembrane delivery carrier Selecting the appropriate carrier for delivery will allow nucleic acid molecules to reach their site of action and enhance delivery efficiency. Currently used nucleic acid delivery vectors can be divided into two major categories: viral and non-viral vectors. Viral carrier transport efficiency is high, but there are safety issues. Non-viral vectors have attracted attention because of their advantages such as low immunogenicity, easy production, and non-tumorigenicity. The construction of safe, effective, and controllable vectors is the focus of current gene therapy research. This review presents the current types of nucleic acid delivery vehicles, which focuses on comparing their respective advantages and limitations, and proposes a novel delivery system, RNTs, a novel nanomolecular material, introducing the characteristics and nucleic acid delivery process of RNTs and their latest applications.

Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism.

MET, the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met-Emx1, and fully inactive homozygous Met-Emx1 mice. Met-Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met-Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met-Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met-Emx1 mice.

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. SIGNIFICANCE STATEMENT: A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention.

Outcomes of liver resection for intrahepatic stones: a comparative study of unilateral versus bilateral disease.

OBJECTIVE: This study aimed to compare the outcomes of liver resection for unilateral and bilateral intrahepatic stones. BACKGROUND: Hepatectomy is effective in treating intrahepatic stones accompanied by biliary stricture or segmental atrophy. The outcomes between unilateral and bilateral intrahepatic stones may be varied because of different complexity of these 2 subtypes of disease. METHODS: From January 1992 to December 2008, 718 consecutive patients with intrahepatic stones underwent elective hepatectomy in our center were reviewed. The outcomes of patients with unilateral stones (n = 461) and bilateral stones (n = 257) were compared. The consistency between extent of liver resection (ELR) and stone-affected segments (SAS) was classified into 2 categories: ELR = SAS and ELR < SAS. The risk factors of stone recurrence were identified by Cox regression model. RESULTS: The immediate stone clearance rates of the unilateral group and the bilateral group were 93.5% and 71.1%, respectively. Postoperative cholangioscopic lithotomy raised the clearance rates to 99.3% and 90.2%, respectively. The surgical morbidities were 20.4% and 38.5%, respectively. The hospital mortality rates of both groups were 0.4%. The 5-year stone recurrence rates were 6.2% and 16.7%, respectively. Cox regression analysis showed that stone distribution (hazard ratio [HR] = 2.462, P = 0.007) and consistency between ELR and SAS (HR = 3.100, P = 0.002) were independent prognostic factors for stone recurrence. CONCLUSIONS: Generally, patients with unilateral stones have better outcomes than those with bilateral stones after hepatectomy associated with cholangioscopic lithotomy. But for the patients with ELR equals to SAS, the stone recurrence rates of unilateral and bilateral stones are low and comparable.

PKCα take part in CCR7/NF-κB autocrine signaling loop in CCR7-positive squamous cell carcinoma of head and neck.

Metastatic squamous cell carcinoma of head and neck (SCCHN) has been shown to express chemokine receptor 7 (CCR7). The role of nuclear factor-κB (NF-κB) in propagating an autocrine signaling loop in CCR7-positive SCCHN cells may provide a clinically useful biomarker of disease status and response to therapy. In this article, we hypothesized that PKCα might be involved in the CCR7/NF-κB autocrine signaling loop. Results showed that CCL19 induced the activation of PKCα, and the increased activity of PKCα was abolished by CCR7 mAb. PKCα inhibition with Gö6976 led to significant reduction in the activation and nuclear translocation of NF-κB induced by CCL19. Immunohistochemical assay also showed that CCR7 and PKCα were highly expressed in SCCHN and correlated with each other, which was significantly related to lymph node metastasis and clinical stage. Taken together, PKCα is involved in the CCR7/NF-κB autocrine signaling loop.