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Background Reconstruction of hemiglossectomy defects requires careful flap design to avoid adverse functional and aesthetic outcomes. Methods Hemitongue specimens were obtained from minipigs to study the three-dimensional anatomy and to define anatomic landmarks for precise measurements of flap requirement. The concept developed in animal models was then applied to hemiglossectomy reconstruction in clinical practice. Sixty-one patients were randomly enrolled into the following two groups: a "five-point eight-line segment" (FIPELS) flap design group (28 patients) and a conventional group (33 patients). Functional and aesthetic outcomes were compared between the two groups. Results All flaps designed with the FIPELS technique matched the hemiglossectomy defects without the need for flap trimming, thus reducing the operating time (P = .03). Swallowing functions, speech intelligibility, and aesthetic outcomes were superior in the FIPELS group than that in the conventional group (P Conclusions The FIPELS flap design for hemiglossectomy reconstruction yields improved functional and aesthetic outcomes compared to a conventional flap design.

In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MS

BACKGROUND Poor adherence to sublingual immunotherapy (SLIT) has become a major cause of unsatisfactory clinical efficacy for patients with allergic rhinitis (AR). This study was designed to identify the effect of different first prescription lengths on the adherence to SLIT. METHODS The clinical data of 306 patients with AR who started SLIT between January 2017 and June 2018 were retrospectively reviewed. Patients were divided into 3 groups according to the length of their first prescription (group A: less than 3 months, group B: 3 to 6 months, group C: more than 6 months). The numbers of adherent or nonadherent patients in each group and the main reasons of nonadherence were analyzed. RESULTS Groups A, B, and C included 102, 161, and 43 patients, respectively. The average lengths of the first prescription for group A, B, and C were 62.52 ± 17.63, 102.21 ± 9.22, and 189.07 ± 17.97 days. There were significance differences among the 3 groups (p < 0.05). There were 42 (41.18%), 112 (69.57%), and 37 (86.05%) adherent patients in group A, B, and C. There were 60 (58.82%), 49 (30.43%), and 6 (13.95%) nonadherent patients in group A, B, and C. There were significant differences in the proportions of adherent and nonadherent patients among the 3 groups (p < 0.05). The following reasons were cited for nonadherence to SLIT: the long course of SLIT; inconvenience of getting the prescription; ineffectiveness; side effects; and other reasons. CONCLUSION Under certain conditions, 6 months is recommended as the standard length for the first prescription, which can significantly improve adherence to SLIT in patients with AR.

As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine. Herein, it can be shown that posttraumatic administration of ketamine at a sub-anesthetic dose (10mg/kg ketamine, every 24h up to 7days) can prevent the TBI-induced production of IL-6 and TNF-α, attenuate deficits of dendrites and spines and exert beneficial effects on memory and behavior. Moreover, studies show that ketamine may activate the mTOR signaling pathway by p-mTOR induction to down-regulate the expression of crucial autophagic proteins such as LC3 and Beclin-1. According to these findings, ameliorating secondary brain injury and anti-inflammatory properties is closely related to the neuroprotection of ketamine, which supports the use of ketamine as a potential therapy for patients with TBI to alleviate functional deficits.

The balance between self-renewal and differentiation of adult neural stem cells (aNSCs) is essential for the maintenance of the aNSC reservoir and the continuous supply of new neurons, but how this balance is fine-tuned in the adult brain is not fully understood. Here, we investigate the role of SIRT1, an important metabolic sensor and epigenetic repressor, in regulating adult hippocampal neurogenesis in mice. We found that there was an increase in SIRT1 expression during aNSC differentiation. In Sirt1 knockout (KO) mice, as well as in brain-specific and inducible stem cell-specific conditional KO mice, the proliferation and self-renewal rates of aNSCs in vivo were elevated. Proliferation and self-renewal rates of aNSCs and adult neural progenitor cells (aNPCs) were also elevated in neurospheres derived from Sirt1 KO mice and were suppressed by the SIRT1 agonist resveratrol in neurospheres from wild-type mice. In cultured neurospheres, 2-deoxy-D-glucose-induced metabolic stress suppressed aNSC/aNPC proliferation, and this effect was mediated in part by elevating SIRT1 activity. Microarray and biochemical analysis of neurospheres suggested an inhibitory effect of SIRT1 on Notch signaling in aNSCs/aNPCs. Inhibition of Notch signaling by a γ-secretase inhibitor also largely abolished the increased aNSC/aNPC proliferation caused by Sirt1 deletion. Together, these findings indicate that SIRT1 is an important regulator of aNSC/aNPC self-renewal and a potential mediator of the effect of metabolic changes.

Background Trans-resveratrol-3-O-glucoside (TRG), isolated from the Chinese traditional herbal medicine Huzhang, has been shown to have a wide range of pharmacological benefits. Purpose The aim of this study is to investigate the pharmacokinetics, tissue distribution and excretion of TRG and its metabolites, (TRN (trans-resveratrol-3-O-glucuronide) and TR (trans-resveratrol)), following a single intragastric (i.g.) administration of TRG in rats. Study design To evaluate the pharmacokinetic properties of TRG, TRN and TR, groups of rats were administrated a single i.g. dose of either 75, 150 or 300 mg/kg TRG. The absolute bioavailability of TRG was estimated from the ratios of AUC0-∞ values for oral and intravenous administration. Tissue distributions of TRG, TRN and TR in rats were investigated following a single i.g. administration to four groups at 150 mg/kg dosage of TRG. For urinary, fecal and biliary excretion study, TRG, TRN and TR excretions were recovered from a group of rats administered a single i.g. dose of 150 mg/kg TRG. Methods The levels of TRG, TRN and TR in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive LC-UV method. The precision was below 10.0%, and the accuracy was within ±9.9% for TRG, TRN and TR. Results The concentrations of TRN were markedly higher than those of TRG and TR in plasma, urine and bile. TRG, TRN and TR showed linear dynamics in dose range of 75–300 mg/kg TRG. TRG had poor absolute bioavailability in rats. The major distribution tissues of TRG, TRN, and TR in rats were in the digestive tract. TRG, TRN and TR were all eliminated from tissues quickly. TRG was mostly excreted via the renal route in the form of TRN, which accounted for 52.8% of the administered dose up to 72 h. Conclusion Following a single i.g. administration to rats TRG was easily absorbed and rapidly converted to the metabolites TR and TRN. These metabolites were found to be mainly excreted by the kidneys.

The main purpose of this study was to illustrate the effect of borneol on pharmacokinetics of salvianolic acid B (SalB) in rats after oral administration of SalB with different doses of borneol. The concentrations of SalB in rat plasma were determined by an established and validated LC-MS/MS method. Our data showed that when 20, 40, and 80 mg kg⁻¹ of borneol were orally administrated with SalB at 50 mg kg⁻¹, C (max) of SalB was increased by 18.4%, 55.8%, and 103.2% compared with that of SalB alone. And AUC(0-t) of SalB in plasma was increased by 14.4%, 48.5%, and 123.3%, respectively. The results indicated that borneol is able to enhance the intestinal absorption and relative bioavailability of SalB, with a positive dose-dependent relationship. The described herb-drug interactions might prove the scientific rationality of the compatible ratio of traditional Chinese medicines.

A procedure for the high-performance liquid chromatographic determination of vertilmicin in rat serum was described using pre-column derivatization. The serum proteins were precipitated with acetonitrile and vertilmicin in the supernatant was derivatized with 1-fluoro-2,4-dinitrobenzene. Etimicin was selected as the internal standard. The mobile phase consisted of methanol--20mM ammonium acetate (80:20, v/v), and flow-rate was 0.9 ml/min. Ultraviolet detection was set at 365 nm. The reaction products were chromatographed on a C(18) column kept at 40 degrees C. A good linearity was found in the range of 0.5-250 microg/ml. Both intra- and inter-day precisions of vertilmicin, expressed as the relative standard deviation, were less than 7.4%. Accuracy, expressed as the relative error, ranged from -0.1 to 3.6%. The mean absolute recovery of vertilmicin at three different concentrations was 92.5%. Serum volumes of 50 microl were sufficient for the determination of vertilmicin. The method was proved suitable for the pharmacokinetic study of vertilmicin in rats.

Tissue engineering combines the principles of cell biology, engineering and materials science to develop three-dimensional tissues to replace or restore tissue function. Tissue engineered skin (TE-skin) is one of most advanced tissue constructs. However, much clinical providence demonstrates the TE-skin may not be viewed as the equal of skin grafts, the contributions to accelerate the closure of wound were come mainly from various growth factor. These growth factors respond to its environment to bring about the desired effect. In our hypothesis, this three-dimensional skin substitute could be genetically modified with various growth factor and transplanted in order to deliver therapeutic proteins locally and systemically for the treatment of trauma. The likelihood of transgened TE-skin plays function as a pharmacological agent suggests a wide range of therapeutic applications. In future, the TE-skin could be design as gene delivery to enhance potential capacity for treatment of burns, chronic wounds and even systemic diseases.

Despite efforts in peripheral nerve injury and regeneration, it is difficult to achieve a functional recovery following extended peripheral nerve lesions. Even if artificial nerve conduit, cell components and growth factors can enhance nerve regeneration, integration in peripheral nerve repair and regeneration remains yet to be explored. For this study, we used chitosan/gelatin nerve graft constructed with collagenous matrices as a vehicle for Schwann cells and transforming growth factor-β1 to bridge a 10-mm gap of the sciatic nerve and explored the feasibility of improving regeneration and reinnervation in rats. The nerve regeneration was assessed with functional recovery, electrophysiological test, retrograde labeling, and immunohistochemistry analysis during the post-operative period of 16 weeks. The results showed that the internal sides of the conduits were compact enough to prevent the connective tissues from ingrowth. Nerve conduction velocity, average regenerated myelin area, and myelinated axon count were similar to those treated with autograft (p > 0.05) but significantly higher than those bridged with chitosan/gelatin nerve graft alone (p < 0.05). Evidences from retrograde labeling and immunohistochemistry analysis are further provided in support of improving axonal regeneration and remyelination. A designed graft incorporating all of the tissue-engineering strategies for peripheral nerve regeneration may provide great progress in tissue engineering for nerve repair.

Molecular hydrogen, as a novel antioxidant, has been proven effective in treating many diseases. This study aimed to evaluate the therapeutic effects of hydrogen saturated saline in treatment of a rat model of diabetes mellitus and a rat model of insulin resistant.A rat diabetes mellitus model was established by feeding a high fat/high carbohydrate diet followed by injection of a small dose of streptozotocin, and an insulin resistant model was induced with a high glucose and high fat diet. Hydrogen saturated saline was administered to rats with both models conditions on a daily basis for eight weeks. A pioglitazone-treated group and normal saline-treated group served as positive and negative controls. The general condition, body weight, blood glucose, blood lipids, and serum insulin levels of rats were examined at the 8th week after treatment. The oxidative stress indices, including serum superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were also evaluated after eight weeks of treatment using the commercial kits.Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Meanwhile, the therapeutic effects of hydrogen saturated saline were superior to those of pioglitazone. Hydrogen saturated saline markedly attenuated the MDA level and elevated the levels of antioxidants SOD and GSH.Hydrogen saturated saline may improve the insulin resistance and alleviate the symptoms of diabetes mellitus by reducing the oxidative stress and enhancing the anti-oxidant system.

The pharmacokinetics of vertilmicin was investigated in rats and dogs following intramuscular or intravenous administration of vertilmicin. Following a single administration of an intramuscular dose, serum concentrations of vertilmicin peaked at 0.63 h in rats and 0.58 h in dogs. In rats, after intravenous administration of vertilmicin at dosages of 10, 20, and 40 mg/kg, the t 1/2 values for vertilmicin were 0.81, 0.76, and 0.86 h, respectively, while after intramuscular administration of vertilmicin at dose of 20 mg/kg, the t 1/2 value for vertilmicin was 0.79 h. In dogs, after intravenous or intramuscular administration of vertilmicin at a dose of 10 mg/kg, the t 1/2 values for vertilmicin were 0.83 and 0.85 h, respectively. After intravenous dosing to rats vertilmicin was distributed to most organs and tissues, and kidney tissue exhibited the highest exposure, while the tissue with the lowest exposure was the brain. Following single intravenous administration of vertilmicin at a dose of 20 mg/kg to rats, about 81.1% of the vertilmicin was excreted in urine, while only 3.12 and 1.44% of the administered dose was excreted in feces and bile within 48 h. The mean values for the plasma protein binding of vertilmicin were 22.7 and 20.4% in rats and dogs, respectively. These results indicate that vertilmicin was rapidly absorbed and widely distributed into various tissues in rats. The pharmacokinetic behavior of vertilmicin was dose-dependent when increasing doses of vertilmicin were administered intravenously to rats. Renal excretion was the primary elimination route of vertilmicin following intravenous administration to rats.

The present study aimed to investigate the effects of salvianolic acid B (SalB) isolated from Radix Salvia miltiorrhizae on the oral pharmacokinetics of metoprolol (MET) and metoprolol acid (META) in rats. The pharmacokinetic parameters of MET and META were measured after oral (15 mg/kg) administration of MET in rats in the presence and absence of SalB. Compared to the control given MET alone, with the concurrent administration of SalB (50 mg/kg), the AUC and C(max) of MET increased by 51.7% and 27.7%, and the AUC and C(max) of META decreased by 26.5% and 19.6%, respectively. With the presence of SalB, the metabolic ratio was markedly decreased by 50.8%. However, no significant changes were observed in the pharmacokinetic parameters of SalB when it was combined with MET.

To study the metabolism of trans-resveratrol-3-O-glucoside (TRG) in vitro in rat tissues, the incubation with cell-free extracts from rat stomach, duodenum, jejunum, ileum and liver was performed, separately. After TRG was incubated with the tissue extracts at 37 degrees C for up to 90 min, the deglycosylation of TRG was (3.50 +/- 0.24) % for stomach, (65.7 +/- 5.94)% for duodenum, (83.5 +/- 6.43)% for jejunum, (77.6 +/- 6.26)% for ileum and (9.62 +/- 1.21)% for liver, separately. It was observed that the small intestine extracts were more active in deglycosylation of TRG than the liver extract, which suggested that the small intestine mucosa played an important role in deglycosylation of TRG. It was assumed that the deglycosylation of TRG was catalyzed by beta-glucosidase in small intestine mucosa.

To observe effects of oral intake of lead on the expression of Hoxa9 gen and the ability of learning and memory and explore the the toxic molecular mechanisms of lead.Thirty male Wistar rats were chosen and randomly divided into the low lead dosage group, the high lead dosage group and the control group, 10 rats in each group. The low lead dosage group and the high lead dosage group were given respectively 0.06%, 0.2% lead acetate orally while the control group was given distilled water orally. The Y-maze test was used to measure the ability of learning and memory, the graphite heat atomic absorption spectrum method to determine the lead concentration in blood and brain, and the in situ hybridization (ISH) method to determine the expression of Hoxa9 mRNA in brain.(1) The number of electric shocks of the lead poisoned rats were significantly increased over time. The number of electric shocks of the lead poisoning rats was much higher than that of the control group (P0.01) (at the end of the experiment, the low lead dosage group: 31.8 +/- 2.26; the high lead dosage group: 37.3 +/- 1.70; the control group: 18.4 +/- 1.51). (2) The brain of the lead poisoned rats including the hippocampus, the cerebellum and the cerebral cortex were significantly atrophic and the apoptosis and necrosis occurred in the cells of the brain. Purkinje's cells in the cerebellum showed significant necrosis and disappearance. The structure of brain in rats of the control group demonstrated no atrophy. (3) The expression of Hoxa9 mRNA in the lead poisoned rats was significantly decreased compared with the control group. There were few Hoxa9 positive cells in the brain of the lead poisoned rats, but many of them were observed in the control group.Lead may inhibit the expression of Hoxa9 and induce atrophy and necrosis of brain, which gives rise to a damage of learning and memory.

To observe the effect of lead on the expression of c-fos mRNA in hippocampus and cerebellum and the ability of learning and memory in rat, and to observe the antagonistic action of Gastrodia elata and E-gelatin on the effect mentioned above.Rats were exposed to lead acetate (0.2 g x kg(-1) x d(-1) and 0.1 g x kg(-1) x d(-1)). The single and combined administration of Gastrodia elata (4 g x kg(-1) x d(-1)) and E-gelatin (1 g x kg(-1) x d(-1)) were conducted at the same time. Blood lead concentration in rats were measured. The ability of learning and memory by Y-maze test were examined. The expression of c-fos mRNA in hippocampus and cerebellum during Y-maze test were observed by in situ hybridization (ISH).(1) Blood lead concentrations were significantly increased in both high and low doses of lead-exposed rats (P0.01). But there were no differences among high dose groups or low dose groups (P0.05). (2) In Y-maze test, the number of electric stroke during learning in lead-exposed group was significantly increased (P0.01) while that in Gastrodia elata and E-gelatin groups was significantly decreased (P0.05), and that in combined use group was more significantly decreased (P0.01). (3) There were much more deep-colored c-fos positive cells in CA3 area of hippocampus in low dose of Pb-exposed with Gastrodia elata + E-gelatin group. These cells were also found in high Pb with combined use or single use group, but which were not so densely distributed as the former. And they were hardly found in high and low doses of Pb alone groups. The changes of expression of c-fos cells in cerebellam were similar to those in hippocampus.The down regulation of c-fos expression may be one of the molecular mechanism of lead-induced impairment of learning and memory. Gastrodia elata and E-gelatin may antagonize the effect of lead on c-fos expression, and combined use of both drugs may potentiate the antagonism.

To observe the counteraction of Gastrodia elata and E-gelatin on the effect of subchronic lead poisoning on the ability of learning and memory and the ultrastructure in hippocampus.Subchronic lead acetate exposure was given to rats (0.2 g x kg(-1) x d(-1)). Single and combined administration of Gastrodia elata (4 g x kg(-1) x d(-1)) and E-gelatin (1 g x kg(-1) x d(-1)) were conducted at the same time. Pb concentration in blood, and the ability of learning and memory (Y-maze test) of rats were measured. Ultrastructure of CA3 pyramidal cells in hippocampus under transmission electron microscope was observed.Blood Pb concentrations in each group (Pb group: 690.6 micro g/L, Pb + Gastodiae eleta group: 688.8 micro g/L, Pb + E-gelatin group: 663.8 micro g/L, Pb + combined group: 667.2 micro g/L) were higher than that in the control (28.24 micro g/L, P0.01). But there was no significant difference (P0.05) among these groups. In Y-maze test, the number of electric stroke in Pb group is higher than that in control (P0.01). Gastrodia elata or E-gelatin used singly could significantly reduce the number of electric stroke of lead-exposed groups (P0.05 in the first month and P0.01 in the second and third month). And the effect of combined use of them was more efficient than single use (P0.01). Under electron microscope, no anomaly was seen in the pyramidal cells of CA3 area in hippocampus of control group. But there was significant anomaly such as neucleus separation in the cells of Pb exposed group. In Pb-Gastrodia elata group, there were some stress response phenomena such as the occurrence of huge mitochondria while in Pb-E-gelatin group, the anomaly was mild. The cells in the CA3 area in hippocampus of the pb-Gastrodia-E-gelatin group were almost normal, and also showed some stress response phenomena.Gastrodia elata and E-gelatin may protect the neurons in CA3 area of hippocampus against damage induced by lead to improve the ability of learning and memory, and they have synergistic effect.

Background Young neurons in the developing brain establish a polarized morphology for proper migration. The PIWI family of piRNA processing proteins are considered to be restrictively expressed in germline tissues and several types of cancer cells. They play important roles in spermatogenesis, stem cell maintenance, piRNA biogenesis, and transposon silencing. Interestingly a recent study showed that de novo mutations of PIWI family members are strongly associated with autism. Results Here, we report that PIWI-like 1 (PIWIL1), a PIWI family member known to be essential for the transition of round spermatid into elongated spermatid, plays a role in the polarization and radial migration of newborn neurons in the developing cerebral cortex. Knocking down PIWIL1 in newborn cortical neurons by in utero electroporation of specific siRNAs resulted in retardation of the transition of neurons from the multipolar stage to the bipolar stage followed by a defect in their radial migration to the proper destination. Domain analysis showed that both the RNA binding PAZ domain and the RNA processing PIWI domain in PIWIL1 were indispensable for its function in neuronal migration. Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons. Conclusions PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs). Our finding of PIWIL1’s function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism. Electronic supplementary material The online version of this article (doi:10.1186/s13041-015-0131-0) contains supplementary material, which is available to authorized users.

Background The morphogenesis of the cerebral cortex depends on the precise control of gene expression during development. Small non-coding RNAs, including microRNAs and other groups of small RNAs, play profound roles in various physiological and pathological processes via their regulation of gene expression. A systematic analysis of the expression profile of small non-coding RNAs in developing cortical tissues is important for clarifying the gene regulation networks mediating key developmental events during cortical morphogenesis. Results Global profiling of the small RNA transcriptome was carried out in rat cerebral cortex from E10 till P28 using next-generation sequencing technique. We found an extraordinary degree of developmental stage-specific expression of a large group of microRNAs. A group of novel microRNAs with functional hints were identified, and brain-enriched expression and Dicer-dependent production of high-abundant novel microRNAs were validated. Profound editing of known microRNAs at “seed” sequence and flanking sequence was observed, with much higher editing events detected at late postnatal stages than embryonic stages, suggesting the necessity of microRNA editing for the fine tuning of gene expression during the formation of complicated synaptic connections at postnatal stages. Conclusion Our analysis reveals extensive regulation of microRNAs during cortical development. The dataset described here will be a valuable resource for clarifying new regulatory mechanisms for cortical development and diseases and will greatly contribute to our understanding of the divergence, modification, and function of microRNAs.