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PDF file - 746K, Forest plot of overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival in OSCC patients treated with surgery and post-operative radiotherapy with and without TPF induction chemotherapy.

PDF file - 81K, Supplemental table S1: Survival comparison between the cN2 patients treated with and without TPF induction chemotherapy. Supplemental table S2: Univariate Cox model analysis. Supplemental table S3: Multivariate Cox model analysis with interaction analysis. Supplemental table S4: Correlation between cyclin D1 expression and response to TPF induction chemotherapy. Supplemental table S5: Survival comparison between the cN2 patients treated with and without TPF induction chemotherapy according to cyclin D1 expression.

Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients with cancer with biomarker detection. To investigate the prognostic and predictive values of cyclin D1 expression in patients with oral squamous cell carcinoma (OSCC) who were treated in a prospective, randomized, phase III trial evaluating standard treatment with surgery and postoperative radiotherapy preceded or not by induction docetaxel, cisplatin, and 5-fluorouracil (TPF), immunohistochemical staining for cyclin D1 was conducted in pretreatment biopsy specimens of 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Cyclin D1 index was estimated as the proportion of tumor cells with cyclin D1 nuclear staining. A low cyclin D1 expression predicted significantly better overall survival (OS; P = 0.001), disease-free survival (P = 0.005), locoregional recurrence-free survival (P = 0.003), and distant metastasis-free survival (DMFS; P = 0.002) compared with high cyclin D1 expression. Cyclin D1 expression levels were not predictive of benefit from induction TPF in the population overall. However, patients with nodal stage cN2 whose tumors had high cyclin D1 expression treated with TPF had significantly greater OS (P = 0.025) and DMFS (P = 0.025) when compared with high cyclin D1 cN2 patients treated with surgery upfront. Patients with low cyclin D1 level or patients with cN0 or cN1 disease did not benefit from induction chemotherapy. This study indicates that cN2 OSCC patients with high cyclin D1 expression can benefit from the addition of TPF induction chemotherapy to standard treatment. Cyclin D1 expression could be used as a biomarker in further validation studies to select cN2 patients that could benefit from induction therapy. Mol Cancer Ther; 12(6); 1112–21. ©2013 AACR.

PDF file - 3255K, Subgroup analysis of overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis free-survival in 232 OSCC patients with low and high cyclin D1 expression

PDF file - 2826K, Overall survival (A), disease-free survival (B), locoregional recurrence-free survival (C), and distant metastasis-free survival (D) in 232 OSCC patients with low and high cyclin D1 expression.

PDF file - 10421K, Immunohistochemical staining for cyclin D1, negative (A), weak positive (B), and strong positive staining (C), original magnification �200.

Venous malformations (VMs) are congenital vascular malformations characterized by a chronically enlarged and malformed venous cavity. Although TIE2 mutation has been commonly recognized as a vital genetic landscape in VMs, the role of TIE2 in regulating the contraction function of smooth muscle cells remains unclear. We generated mouse models through endothelial germline/somatic expression of Tie2-R848W, which has been identified as a typical mutation in autosomal inherited venous malformations, multiple cutaneous and mucosal venous malformation (VMCM). Tie2-R848Wfl/fl;Tie2Cre+ mice develop pulmonary vascular malformations with internal hemorrhage. Tie2-R848W in Tie2-R848Wfl/fl;AplnER+ mice induces postnatal retinal vascular malformations. Accordingly, we demonstrate that dysregulated function and phenotypic transition of vascular smooth muscle cells (VSMCs) may be the pathogenic basis of Tie2-related vascular malformations. The phenotypic transition of VSMCs was further identified in human VMs of the head and neck carrying TIE2 mutations and in an in vitro model. Downregulated ion transmembrane transport and TNFSF10 may play a substantial role in initiating the phenotypic transition process of VSMCs. In conclusion, germline/somatic TIE2 mutation in ECs might induce an abnormal regulatory relationship between ECs and VSMCs, which is highly associated with the phenotypic transition of VSMCs. Weakened contractility and abnormal proliferation induce a chronic expansion cavity and thickening of the muscle layer, which may develop into venous malformation.

To investigate the clinicopathological characteristics, immunoprofile, and molecular alterations of adenoid cystic carcinoma (ACC) in children and young adults.Twelve cases of ACC were included. MYB, MYBL1, Ki-67, type IV Collagen, Laminin, and LAMB1 expression were detected by immunohistochemistry. MYB and MYBL1 rearrangements were detected by fluorescence in situ hybridization.Among 12 patients, four were female and eight were male. Seven cases (58.3%) located in major salivary glands and eight cases (66.7%) were classified as Grade I. Ten tumors (83.3%) had collagenous and hyalinized stroma. MYB was positive in 83.3% cases, and the average Ki-67 labeling index (LI) was 8.3%. LAMB1, type IV Collagen, and Laminin were positive in 91.7%, 66.7%, and 58.3% cases, respectively. Besides, three out of eight tumors had MYB rearrangement. Cases without MYB rearrangement were negative for MYBL1 expression and MYBL1 rearrangement. The average follow-up time was 91.8 months. Four patients had recurrent diseases.ACC in children and young adults was seen more frequently in males and major salivary glands. Most cases had ECM and hyaline stroma. Grade III tumors, higher Ki-67 LI, negative expression of type IV Collagen, and Laminin showed a tendency of higher recurrence rate.

Novel neoadjuvant therapy regimens are needed to improve the outcomes of patients with locally advanced resectable oral squamous cell carcinoma (OSCC). We conducted a prospective, open-label, single-arm trial (n = 21, NCT04393506) to determine the safety and feasibility of neoadjuvant camrelizumab (an anti-PD-1 antibody) plus apatinib (a VEGFR inhibitor) for locally advanced resectable OSCC. The primary endpoints were safety and major pathological response (MPR). Neoadjuvant camrelizumab plus apatinib was well-tolerated and the MPR rate was 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃ 10 had MPR. Additionally, patients achieving MPR showed more CD4+ T cell infiltration and a higher CD8+/FoxP3+ ratio than those without MPR (p < 0.05), and decreased CD31 and ɑ-SMA expression were observed after neoadjuvant therapy. Our findings demonstrate that neoadjuvant therapy with a chemo-free combination of camrelizumab and apatinib is safe and yields a promising MPR rate, supporting further trials.

Phosphorization of metal oxides/hydoxides to promote electronic conductivity as a promising strategy has attracted enormous attention for improving the electrochemical properties of anode material in lithium ion batteries. For this article, selective phosphorization from NiCo2O4 to NiO/Ni2Co4P3 microspheres was realized as an efficient route to enhance the electrochemical lithium storage properties of bimetal Ni-Co based anode materials. The results show that varying phosphorizaed reagent amount can significantly affect the transformation of crystalline structure from NiCo2O4 to intermediate NiO, hybrid NiO/Ni2Co4P3, and, finally, to Ni2Co4P3, during which alterated sphere morphology, shifted surface valance, and enhanced lithium-ion storage behavior are detected. The optimized phosphorization with 1:3 reagent mass ratio can maintain the spherical architecture, hold hybrid crystal structure, and improve the reversibly electrochemical lithium-ion storage properties. A specific capacity of 415 mAh g−1 is achieved at 100 mA g−1 specific current and maintains at 106 mAh g−1 when the specific current increases to 5000 mA g−1. Even after 200 cycles at 500 mA g−1, the optimized electrode still delivers 224 mAh g−1 of specific capacity, exhibiting desirable cycling stability. We believe that understanding of such selective phosphorization can further evoke a particular research enthusiasm for anode materials in lithium ion battery with high performances.

Background: To evaluate the feasibility ofdelineating subvolume target in brain tumor radiotherapy using gd-based contrast clearance difference.Methods：Twenty-six patients with malignant brain tumor were scanned with MRI. The first and second acquisitions of standard T2-weighted images (T2WI) andT1-weighted images (T1WI) were respectively performed?> at 5 minutes and 60 minutesafter injection of contrast agent. Delayed contrast extravasation MRI(DCEM) computed by Brainlab concludesregions of contrast agent clearance which represent active tumor，andregions of contrast accumulation which represent non-tumor tissues. Based on T2WI images,14 patients were divided into group A and group B, with andwithout liquefaction necrosis, respectively. Then,gross target volume (GTV) was delineated on T1WI images. Based on the GTV, active tumor (GTV tumor) and non-tumorregions(GTV non-tumor) were delineated on T1WI-DCEM fusion images, whileliquefaction necrosis (GTVliquefaction)and non-liquefaction(GTVnon-liquefaction)were delineated on T1-T2WI fusion images. Finally, the differences between different subvolumes were compared by paired t-test.Results：In group A,the mean value of GTVA was 21.38±25.70 cm3, and the GTVnon-liquefaction and GTVliquefaction were 13.65±18.15cm3 and6.30±7.57cm3, respectively. The GTV tumor was 10.40±13.52 cm3 whilethe GTV non-tumor was 9.55±14.57 cm3, The GTVnon-liquefaction increased by an average of 28.2%（P＜0.05）,compared to GTV tumor . While the GTV non-tumor increased by an average of 46.3% (P＜0.05), compared tothe GTVliquefaction.In group B, the mean value of GTVB on enhanced T1WI was4.39±3.75 cm3. The GTV non-tumorreduced by an average of 50.3% (P＜0.05) , compared totheGTV tumor.Conclusion：Comparedto T2WI, the DCEM has advantages in identifyingthe liquefaction areaand could clearly differentiatesubvolume of active tumor from non-liquefaction necrosis.DCEMis meaningful in guiding the delineation of subvolume in primary and metastatic brain tumors.

Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used (68)Ga, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by (68)Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of (89)Zr and (68)Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of (68)Ga-labeled CAR T cells is only one twenty-fourth of (89)Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of (68)Ga instead of (89)Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.

To construct clinical practice system, making up for the shortcomings in the instructional framework of oral histology and pathology, promoting the integration of theory and clinical practice, and enhancing teaching quality of long-term students of stomatology.Laying down clinical practice plans and formulating technical operation criteria for pathological experiments, constructing a complete database and training high-level teachers, and evaluating through the following three aspects: practice assessment, teacher-student symposium and questionnaire survey.After completing the clinical practice, the students got the average score of 89.37. In questionnaire survey, the students generally expressed that they had a better understanding of the specialized characteristics and routine skills of the speciality, and improved their practical ability, thus stimulating their interest in self-directed learning.The construction and practice of clinical practice system of oral histology and pathology can effectively improve the educational objectives and teaching quality of this discipline, which will play a positive role in scientific research and future medical work of long-term students majoring in stomatology.

To determine whether ectopic thyroid had the same computed tomography (CT) value as orthotopic thyroid. Twenty-one patients with 23 ectopic thyroids and 23 controls with orthotopic thyroids underwent CT scans and were included in this retrospective study. The CT images were reviewed in a blinded fashion by two radiologists. Independent-Samples T-test was used for comparison of CT attenuation values between two groups. Ectopic thyroids had significantly lower non-enhanced attenuation (91.04 ± 5.97 Hounsfield Units vs. 106.56 ± 4.06 Hounsfield Units, P = 0.038) and contrast-enhanced attenuation (141.32 ± 6.42 Hounsfield Units vs. 169.82 ± 4.30 Hounsfield Units, P = 0.001) values than orthotopic thyroids. Ectopic thyroids have lower CT attenuation values than orthotopic thyroids probably due to the structural or functional abnormalities. The dysgenesis and pathological changes of the ectopic thyroids may contribute to functional deficiency which finally leads to decrease of the CT attenuation values.

This paper investigates Cauchy problems for nonlinear fractional time–space generalized Keller–Segel equation D t β 0 c ρ + ( − △ ) α 2 ρ + ∇ ⋅ ( ρ B ( ρ ) ) = 0 , where Caputo derivative D t β 0 c ρ models memory effects in time, fractional Laplacian ( − △ ) α 2 ρ represents Levy diffusion and B ( ρ ) = − s n , γ ∫ R n x − y | x − y | n − γ + 2 ρ ( y ) d y is the Riesz potential with a singular kernel which takes into account the long rang interaction. We first establish L r − L q estimates and weighted estimates of the fundamental solutions ( P ( x , t ) , Y ( x , t ) ) (or equivalently, the solution operators ( S α β ( t ) , T α β ( t ) ) ). Then, we prove the existence and uniqueness of the mild solutions when initial data are in L p spaces, or the weighted spaces. Similar to Keller–Segel equations, if the initial data are small in critical space L p c ( R n ) ( p c = n α + γ − 2 ), we construct the global existence. Furthermore, we prove the L 1 integrability and integral preservation when the initial data are in L 1 ( R n ) ∩ L p ( R n ) or L 1 ( R n ) ∩ L p c ( R n ) . Finally, some important properties of the mild solutions including the nonnegativity preservation, mass conservation and blowup behaviors are established.

In this paper, Lie point symmetry group of the Harry-Dym type equation with Riemann-Liouville fractional derivative is constructed. Then complete subgroup classification is obtained by means of the optimal system method. Finally, corresponding group-invariant solutions with reduced fractional ordinary differential equations are presented via similarity reductions.

Homocysteine (Hcy) regulates endothelial injury and methylation status of key genes in cerebral ischemia. Thrombomodulin (TM) may be protective against cerebral ischemia by downregulating coagulation. However, it remains unclear whether Hcy involved in methylation and expression of TM in cerebral infarction (CI). Here, we find patients with cerebral infarction had a higher TM methylation level than controls (74.2% vs 47.5%, X(2) = 14.724, P = 0.00), which are positively correlated with plasma levels of tHcy (r = 0.701, P = 0.00) and negatively related to mRNA expression of TM (r = -0.711, P = 0.00). Plasma levels of tHcy (t = 7.566, P = 0.00) and sTM (t = 17.268, P = 0.00) are significantly higher in cases than in controls. Our data indicate hyperhomocysteine leads to hypermethylation of the TM gene and further induces TM gene silencing, which may play an important role in the occurrence and development of CI. Plasma higher concentrations of sTM in cases are not caused by TM expression and may be only a result of Hcy induced endothelial injury.

OBJECTIVE: To study the association between overweight/obesity in parents before maternal pregnancy and the development of autism spectrum disorders (ASD) in offspring. METHODS: A total of 36 children who were diagnosed with ASD (ASD group) and 72 normal children matched for sex and age (control group) were enrolled. A questionnaire survey was performed to collect the general information, including body height and body weight of parents before maternal pregnancy and maternal weight gain during pregnancy. Univariate and multivariate logistic regression analyses were used to investigate the association between overweight/obesity in parents before maternal pregnancy and ASD in offspring. RESULTS: The ASD group had a significantly higher detection rate of overweight/obesity in the father than the control group (56% vs 32%; P=0.018) before maternal pregnancy. The univariate and multivariate logistic regression analyses showed that overweight/obesity of the father before maternal pregnancy was a risk factor for ASD in offspring (OR=2.66 and 2.58 respectively; P < 0.05). CONCLUSIONS: Overweight/obesity of the father before maternal pregnancy is an independent risk factor for ASD in offspring, and therefore, it is important for the father to control his body mass index within the normal range before maternal pregnancy.

In this paper, a consistent Riccati expansion method is developed to solve nonlinear fractional partial differential equations involving Jumarie's modified Riemann–Liouville derivative. The efficiency and power of this approach are demonstrated by applying it successfully to some important fractional differential equations, namely, the time fractional Burgers, fractional Sawada–Kotera, and fractional coupled mKdV equation. A variety of new exact solutions to these equations under study are constructed.

Copper nanoparticles (Cu NPs) spaced reduced graphene oxide (rGO) films are fabricated by integrating electrophoresis deposition (EPD) with thermal H2 annealing. The Cu NPs are formed through thermal aggregation and reduction of Cu(II) ions which are counter cations of GO. By tuning the annealing temperature from 400 to 850 °C, the mean diameter of the Cu NPs increases from 35 to 124 nm. Chemical characterizations reveal that the EPD technique may partially remove the O-containing groups of the GO film, while complete removal of the O-containing groups and effective repair of the graphene defects are achieved by thermal H2 treatment. With the implantation of Cu NPs, the resultant rGO/Cu NP films exhibit high porosity and amazing electric conductivities, enabling their direct use as lithium-ion battery (LIB) electrodes (vs. Li/Li+) without a general current collector, binder, and other additives. This novel LIB has a high charge/discharge capacity (>463 mA h g−1), an excellent reversibility, and a high coulombic efficiency (nearly 100%) for 300 cycles at a current density of 0.2 A g−1. It also exhibits good rate capacity: 849 mA h g−1@0.1 A g−1, 618 mA h g−1@0.2 A g−1, 516 mA h g−1@0.3 A g−1, and 470 mA h g−1@0.5 A g−1. Our new technique provides advanced design strategies for high performance LIBs and ultracapacitors, which might be used for mobile phone and electrical vehicles with unprecedented performances.

Geosynthetic clay liners (GCL) have been widely used as impermeable materials in landfill and other projects due primarily to their low hydraulic conductivity (k). Recently, GCLs are increasingly considered to contain mining leachates which may result in the degradation of their hydraulic performance. This study reports the hydraulic performance of a GCL under the mining solution from a mine in Hunan Province. Flexible-wall hydraulic conductivity test and free swell index test were conducted on GCL and bentonite specimens. The results indicate that the swell index decreased from 31 mL/2 g (in water) to 22 mL/2 g (under the mining solution). The hydraulic conductivity unexpectedly increased from 3 × 10−11 m/s to 4 × 10−9 m/s when changing the permeable solution from water to the mining solution. While if the GCL specimens were prehydrated with water for two days before contacting mining solution, the k value was decreased to an acceptable level (8 × 10−11 m/s). The greater effective stress also imparts a low hydraulic conductivity, the k value dropped from 4 × 10−9 m/s to 1 × 10−10 m/s when the effective stress elevated from 35 kPa to 200 kPa. The results of this study could provide a helpful reference for the application of GCLs under mining solutions.

A manganese oxyhydroxide/three-dimensional reduced graphene oxide (MnOOH/3D-rGO) composite was prepared by a two-step hydrothermal procedure. Powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy analyses show that MnOOH nanoneedles grow on the porous 3D-rGO skeleton. The MnOOH/3D-rGO composite displays a high specific capacitance (327 F g−1 at 0.2 A g−1 in 1.0 M Na2SO4 electrolyte) and excellent cycling stability with 96.7% capacitance retention after 1000 cycles. The asymmetric supercapacitors made with MnOOH/3D-rGO and activated carbon exhibit excellent performances in energy storage. At a power density of 378 W kg−1, the devices can deliver a maximum energy density of 52.7 W h kg−1. The excellent electrochemical performance, including high energy density, high specific capacitance and long cycle lifetime, of the MnOOH/3D-rGO composite may be due to the synergistic effect of the 3D interpenetrating microstructure of the conductive rGO and the nanoneedle structure of MnOOH. The 3D-rGO can provide facile routes for the transfer of the ions and electrons and the nanoneedle structure is beneficial for the intercalation–deintercalation processes of Na+ ions in the MnOOH.

Oral histopathology is a course which needs to be combined with theory and practice closely. Experimental course plays an important role in teaching oral histopathology. Here, we aim to explore a series of effective measures to improve the teaching quality of experimental course and tried to train observation, thinking, analysis and problem solving skills of dental students.We re-edited and updated the experimental textbook "guidelines of experimental course of oral histopathology", and published the reference book for experimental course--"color pocket atlas of oral histopathology: experiment and diadactic teaching". The number of clinicopathological cases for presentation and class discussion was increased, and high-quality teaching slides were added and replaced the poor-quality or worn out slides. We established a variety of teaching methods based on the internet, which provided an environment of self-directed learning for dental students. Instead of simple slice-reading examination, a new evaluation system based on computer was established.The questionnaire survey showed that the students spoke positively on the teaching reform for experimental course. They thought that the reform played a significant role in enriching the teaching content, motivating learning interest and promoting self-study. Compared with traditional examination, computer-based examination showed a great advantage on mastering professional knowledge systematically and comprehensively.The measures adopted in our teaching reform not only effectively improve the teaching quality of experimental course of oral histopathology, but also help the students to have a clear, logical thinking when facing complicated diseases and have the ability to apply theoretical knowledge into clinical practice.