Measurement of the distance between tumor micro-foci and gross tumor in rectal cancer pathological specimens: implication on margin distance of clinical target volume treated with high-dose radiotherapy for rectal cancer.

PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

Spatiotemporal photosynthetic physiology responses of remnant Myricaria laxiflora populations to regulated water level fluctuations.

The construction of the Three Gorges-Gezhouba Dam cascade hydropower station has changed the water level fluctuation pattern of the habitats for remnant rare and endangered Myricaria laxiflora populations downstream of the dam. The present study utilized biochemical markers of photosynthetic physiology to evaluate the spatiotemporal responses of remnant populations to human-regulated water level fluctuations. The results showed that the photosynthetic physiological activities of remnant M. laxiflora populations underwent a period of rapid growth, followed by a gradual decline in the growth recovery phase after flooding. During the entire experimental period, photosynthetic physiological activities of remnant M. laxiflora populations changed with prolongation of emergence time: specifically, net photosynthetic rate and stomatal conductance initially decreased and then subsequently increased, intercellular carbon dioxide concentrations peaked at mid-phase and transpiration rate continuously increased. The maximum net photosynthetic rate, apparent photosynthetic quantum efficiency and dark respiration rate in the light-response curves of the plants continuously increased during growth. The water level gradient also significantly affected the photosynthetic physiological activities in the remnant populations, i.e. the photosynthetic physiological activities of high-altitude plants were significantly higher than the middle- and low-altitude plants. The changes in photosynthetic pigment content of plants in remnant populations during the growth recovery phase and the entire growth period were similar to those occurring in photosynthetic activities in plants. Further, canonical correspondence analysis showed that photosynthetic physiological activities in the plants were significantly correlated with changes in water levels, emergence time, elevation gradient, soil water and soil nitrogen contents. Therefore, the artificial regulation of water level fluctuations by large hydropower stations will inevitably affect the photosynthetic activities and growth of remnant M. laxiflora populations.

LncRNA WWC2-AS1 functions AS a novel competing endogenous RNA in the regulation of FGF2 expression by sponging miR-16 in radiation-induced intestinal fibrosis.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) were considered as important gene expression regulators involving various biological processes. In this study, we explored the role of lncRNAs in the pathogenesis of radiation-induced intestinal fibrosis (RIF). METHODS: LncRNAs were screened by microarray (Human LncRNA Array v3.0, Arraystar, Inc.) and the differentially expressed lncRNAs in RIF and non-RIF were analyzed by bioinformatics methods. The expression of WWC2-AS1/miR-16/FGF2 axis was compared on mRNA and protein level between human intestinal CCD-18Co fibroblasts cell lines and subepithelial SEMFs in response to radiation treatment. The significance of WWC2-AS1 in regulating FGF2 associated proliferation, migration, invasion and fibrosis of CCD-18Co and SEMFs by exposure to radiation was analyzed by shRNA (WWC2-AS1 shRNA) knock-down of endogenous WWC2-AS1. RESULTS: WWC2-AS1 and FGF2 level was significantly higher while miR-16 was down-regulated in radiation-treated intestinal tissues. WWC2-AS1 more potently boosted FGF2 expression via reducing miR-16, and WWC2-AS1 shRNA remarkably inhibited FGF2 associated proliferation, migration, invasion and fibrosis of radiation treatment in vitro, further demonstrating physical interaction between miR-16 and WWC2-AS1 in radiation-induced fibrosis progress. CONCLUSIONS: WWC2-AS1 was highly expressed in RIF, may function as a ceRNA in the regulation of FGF2 by binding miR-16. Targeting WWC2-AS1 thus may benefit radiation-induced fibrosis treatment.

Chitosan-Based Polysaccharide-Gated Flexible Indium Tin Oxide Synaptic Transistor with Learning Abilities.

Recently, environment-friendly electronic devices are attracting increasing interest. "Green" artificial synapses with learning abilities are also interesting for neuromorphic platforms. Here, solution-processed chitosan-based polysaccharide electrolyte-gated indium tin oxide (ITO) synaptic transistors are fabricated on polyethylene terephthalate substrate. Good transistor performances against mechanical stress are observed. Short-term synaptic plasticities are mimicked on the proposed ITO synaptic transistor. When applying presynaptic and postsynaptic spikes on gate electrode and drain electrode respectively, spike-timing-dependent plasticity function is mimicked on the synaptic transistor. Transitions from sensory memory to short-term memory (STM) and from STM to long-term memory are also mimicked, demonstrating a "multistore model" brain memory. Furthermore, the flexible ITO synaptic transistor can be dissolved in deionized water easily, indicating potential green neuromorphic platform applications.

Overexpression of NDUFA4L2 is associated with poor prognosis in patients with colorectal cancer.

BACKGROUND: NDUFA4L2 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2, also called NADH-ubiquinone oxidoreductase MLRQ subunit homologue) was clearly enriched in the mitochondrial fraction under hypoxic conditions, and immunofluorescence showed a clear colocalization of NDUFA4L2 and cytochrome c in some tumour cells. However, little study has investigated its prognostic value in colorectal cancer (CRC). METHODS: In our study, mRNA-NDUFA4L2 and protein expression were analysed in 150 cases of CRC and adjacent normal tissues using immunohistochemistry, semi-quantitative reverse transcriptase-polymerase chain reaction. The correlation between NDUFA4L2 expression and clinicopathological factors was evaluated by the Chi-square test. Overall survival of patients was analysed by the Kaplan-Meier method. RESULTS: NDUFA4L2 overexpression was observed in 84% (126/150) of CRC tissues, but only in 24.7% (37/150) of adjacent normal tissues (P < 0.05). Semi-quantitative reverse transcriptase-polymerase chain reaction showed average mRNA expression levels to be 23.34 ± 1.356 and 4.34 ± 1.132 for CRC tissue and adjacent normal tissue (P < 0.05). Statistical analysis showed a significant correlation of NDUFA4L2 expression with histological grade, Dukes' stages, lymph node metastasis and liver metastasis. More importantly, multivariate analysis indicated that overexpression of NDUFA4L2 was an independent prognostic factor for CRC patients (P = 0.002). NDUFA4L2-negative patients had a higher tumour-free/overall survival rate than patients with high NDUFA4L2 expression (P = 0.001 and 0.002, respectively). CONCLUSIONS: Our data suggest that NDUFA4L2 overexpression is associated with tumour progression and a poor prognosis in CRC patients.

Primary NK/T-cell lymphoma of the larynx: Report of 2 cases and review of the English-, Japanese-, and Chinese-language literature.

Natural killer/T (NK/T) -cell lymphoma in the larynx is extremely rare, as only 29 cases have been previously reported in the English-language, Japanese-language, and Chinese-language literature. Its characteristics have never been systematically illustrated. We report 2 new cases of laryngeal NK/T-cell lymphoma, and we discuss the process of the diagnosis of this disease, the choice of treatment, and treatment outcomes. We also summarize all 31 cases reported thus far. Symptoms of laryngeal NK/T-cell lymphoma are difficult to differentiate from those of other laryngeal diseases. The most common laryngeal subsite in the reported cases was the supraglottis, and roughly one-third of these cases involved the cervical lymph nodes. Because of our limited experience with this disease and the difficulties encountered in interpreting the pathologic findings, most patients required multiple biopsies over a few months before their diagnosis was confirmed. The outcome of treatment was generally poor. Radiotherapy, alone or combined with chemotherapy, was superior to chemotherapy alone in treating this disease in its early stages. In view of the frequency of local lymph node metastasis, irradiation fields should cover the entire cervical area. We believe that prompt diagnosis and treatment with radiotherapy are both critical to improving survival for patients with laryngeal NK/T-cell lymphoma.

MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction.

Colorectal cancer (CRC) is the third most common cancer type and the fourth leading cause of cancer­associated mortality worldwide. MicroRNA (miR)­1246 is involved in differentiation, invasion, metastasis and chemoresistance of certain types of tumor cells. CCNG2 encodes an unconventional cyclin homolog, cyclin G2 (CycG2), associated with growth inhibition, which correlated significantly with lymph node metastasis, clinical stage, histological grade and poor overall survival in numerous cancer types. To investigate the regulation of miR­1246 on CycG2 expression, and their effects on proliferation and metastasis of CRC, HCT­116 and LOVO cells were transfected with pre­miR­1246 anti­miR­1246 and their negative controls. It was demonstrated that the expression of miR­1246 was significantly increased in CRC tissues and cell lines, which was the opposite of CycG2. miR­1246 negatively regulated the expression of CycG2 in HCT­116 and LOVO CRC cells. CCNG2 is a direct target of miR­1246 in CRC cells. Overexpression of miR­1246 induced cell proliferation, migration and invasion, while knockdown of miR­1246 inhibited proliferation, migration and invasion in the CRC cells. Upregulation of miR­1246 mediated the malignant progression of CRC and is partly attributed to the downregulation of the expression of CycG2. Consequently, these findings provided a molecular basis for the role of miR­1246/CCNG2 in the progression of human CRC and suggested a novel target for the treatment of CRC.

Inorganic proton conducting electrolyte coupled oxide-based dendritic transistors for synaptic electronics.

Ionic/electronic hybrid devices with synaptic functions are considered to be the essential building blocks for neuromorphic systems and brain-inspired computing. Here, artificial synapses based on indium-zinc-oxide (IZO) transistors gated by nanogranular SiO2 proton-conducting electrolyte films are fabricated on glass substrates. Spike-timing dependent plasticity and paired-pulse facilitation are successfully mimicked in an individual bottom-gate transistor. Most importantly, dynamic logic and dendritic integration established by spatiotemporally correlated spikes are also mimicked in dendritic transistors with two in-plane gates as the presynaptic input terminals.

Memory and learning behaviors mimicked in nanogranular SiO2-based proton conductor gated oxide-based synaptic transistors.

In neuroscience, signal processing, memory and learning function are established in the brain by modifying ionic fluxes in neurons and synapses. Emulation of memory and learning behaviors of biological systems by nanoscale ionic/electronic devices is highly desirable for building neuromorphic systems or even artificial neural networks. Here, novel artificial synapses based on junctionless oxide-based protonic/electronic hybrid transistors gated by nanogranular phosphorus-doped SiO2-based proton-conducting films are fabricated on glass substrates by a room-temperature process. Short-term memory (STM) and long-term memory (LTM) are mimicked by tuning the pulse gate voltage amplitude. The LTM process in such an artificial synapse is due to the proton-related interfacial electrochemical reaction. Our results are highly desirable for building future neuromorphic systems or even artificial networks via electronic elements.

Predictive value of Xrcc1 gene polymorphisms for side effects in patients undergoing whole breast radiotherapy: a meta-analysis.

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

[Effect of early rehabilitation training on radiation-induced trismus in nasopharyngeal carcinoma patients].

BACKGROUND & OBJECTIVE: Many nasopharyngeal carcinoma (NPC) patients could survive for a long time after radiotherapy. But the complications of radiotherapy, such as trismus, severely influence the quality of life of NPC patients. This study was to observe the effect of early rehabilitation training on radiation-induced trismus of NPC patients. METHODS: A total of 108 NPC patients received rehabilitation guidance by doctors at initial radiotherapy and subjected to early rehabilitation training regularly and intensively after radical radiotherapy between Dec. 2003 and Dec. 2004 at Xiangya Hospital of Central South University. They continued on rehabilitation training out of hospital as the same in hospital. According to the data of rehabilitation training obtained by questionnaire at 1 month after radiotherapy, the patients who completed the amount of rehabilitation training (>or=75%) were brought into rehabilitation training group, the others was brought into control group. The distance between two dens incivus medialis (DDIM) of the patients was measured at 1 month and 1 year after radiotherapy. RESULTS: The difference of rehabilitation training score was significantly higher in rehabilitation training group than in control group (9.80+/-3.02. vs.4.75+/-1.90 at 1 month after radiotherapy, P<0.05û 9.00+/-2.67 vs. 2.20+/-0.82 at 1 year after radiotherapy, P<0.05). The occurrence rates of trismus were 44.1% at 1 month and 51.5% at 1 year after radiotherapy in rehabilitation training group, and 60.0% and 85.0% in control group. The reduction of DDIM was significantly smaller in rehabilitation training group than in control group [(0.50+/-0.48) cm vs. (1.20+/-0.74) cm at 1 month after radiotherapy, P<0.05û (0.58+/-0.62) cm vs. (2.42+/-0.84) cm at 1 year after radiotherapy, P<0.01]. CONCLUSIONS: Early rehabilitation training is helpful to decrease the occurrence of trismus in NPC patients after radiotherapy and improve the quality of life of NPC patients.