OBJECTIVETo establish DNA microarrays-based microRNA (miRNA) expression profiles of squamous cell carcinoma of larynx, using archived formalin-fixed paraffin-embedded tissue blocks, and to screen out and identify the differentially expressed miRNAs associated with the biological characteristics of this malignant disease.

METHODSTotal RNA was prepared from the formalin-fixed paraffin-embedded tissue blocks. After quality identification and fluorescent labeling, the RNA samples were hybridized with the Agilent human miRNA microarrays which contains 723 probes for human miRNAs. The data was processed with the softwares GeneSpring GX and R-Project.

RESULTSFrom the formalin-fixed paraffin-embedded tumor blocks collected, 24 RNA samples were obtained with the quality accorded to the requirement of miRNA microarray analysis, and both the hybridization and consequent data processing were accomplished. A total of 319 miRNAs were identified and among them 96 were detected in all the 24 formalin-fixed paraffin-embedded blocks of laryngeal carcinoma; and 5 differentially expressed miRNAs (false discovery rate < 0.05) were found to be associated significantly with the lymphatic metastasis of laryngeal squamous cell carcinoma (P < 0.05), including miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425.

CONCLUSIONSHistopathological archives of well-annotated formalin-fixed paraffin-embedded tissue specimens are the valuable resources for miRNA study including to collect RNA samples for miRNA microarray analysis. A panel of differentially expressed miRNAs (miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425) derived from the miRNA expression profile may serve as the potential molecular biomarkers for the prediction of metastasis development in laryngeal squamous cell carcinoma.

Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Gene Expression Profiling ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Lymphatic Metastasis ; MicroRNAs ; metabolism ; Oligonucleotide Array Sequence Analysis ; methods ; Paraffin Embedding

Objective To observe the optimal timing of operation and the therapeutic effect of endoscopic optic nerve decompression for traumatic optic neuropathy (TON). Methods The clinical records of 90 consecutive patients with TON (93 eyes) after head and/or maxillofacial trauma from April 1998 to March 2007 were reviewed and analyzed. All patients were either unresponsive or intolerant to medication before they underwent intranasal endoscopic optic nerve decompression. The time interval between the injury and operation ranged from one day to 97 days (median 5.5 days). Among the 93 eyes, there were 71 eyes with no visual acuity before operation and 22 eyes with residue visual acuity, including light perception in 1 eye, hand movement in 5 eyes, counting fingers in 13 eyes, 0.04 in 1 eye, and 0.1 in 2 eyes. Duration of follow-up ranged from 6 days to two years (median 8 days). Results After decompression, 35 patients (36/93 eyes, 38.7%) showed improvement of visual acuity, 53 patients (55 eyes, 59.1%) remained the same as before operation, while 2 patients (2 eyes, 2.2%) showed decreased visual acuity. Among patients with visual acuity beyond light perception before decompression, 68.2% of them (15/22 eyes) experienced visual improvement ,whereas only 22.9% (8/35 eyes, 0.02 in two eyes) among patients who lost visual acuity immediately after injury, and 36.1% (13/36 eyes, 0.02 in five eyes) among those who lost visual acuity gradually after injury. There was a significant difference in visual improvement between group with visual acuity and group with no visual acuity (X2 = 11. 864, P < 0.01). Among patients with no visual acuity, 41.2% of those (7/17 eyes) who underwent operation within 3 days of injury, experienced improvement in visual acuity, compared with 25.9% (14/54 eyes) for those who underwent the operation more than 3 days after injury. It was indicated that no significant difference in visual improvement between these two groups (X2 = 1.46, P > 0.05). When comparing different sites of fracture, the effect of surgery was the most desirable (55.6%, 10/18 eyes improved) if the fracture occurred simultaneously in both exterior and interior walls of optic canal, followed by the interior wall fracture (45.7%, 21/46 eyes). The operation was less effective if there was no fraction (20% , 4/20 eyes) or if the fracture occurred in exterior wall alone (11.1%, 1/9 eyes). Conclusions Endoscopic optic nerve decompression is a minimally invasive procedure with no adverse cosmetic effects. Early operation is recommended for saving vision, even though visual acuity is lost immediately after injury. However, the satisfactory clinical effects of endoscopic optic nerve decompression require further study.

BACKGROUNDThe ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population.

METHODSSubjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Odds ratios were estimated using a case-control study design by controlling confounding factors.

RESULTSThe A/A genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41, 95% CI 1.03-1.94), increased waist circumference (OR 1.75, 95% CI 1.26-2.42), and increased fast blood glucose (OR 1.49, 95% CI 1.07-2.06) in women. The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37, 95% CI 1.02-1.84).

CONCLUSIONThe polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.

Adult ; Aged ; Cholesterol, HDL ; blood ; Female ; Genotype ; Humans ; Male ; Metabolic Syndrome ; blood ; genetics ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Ghrelin ; genetics

BACKGROUNDThe prevalence of metabolic syndrome (MetS) in hypertensive population in Chinese countryside is unknown. Firstly, this study compared the prevalence of MetS according to National Cholesterol Education Program (NCEP) ATPIII, revised NCEP and International Diabetes Federation (IDF) definitions. Secondly, it investigated the association between MetS, coronary heart disease (CHD) and stroke in patients with hypertension.

METHODSIn this cross sectional study, the cluster sampling method was used. Three MetS definitions were applied to 1418 normal subjects and 5348 hypertensive patients aged 40-75 years in rural areas in China. The agreement between different MetS definitions was estimated by kappa statistics. Logistic regression analyses determined the association between MetS defined by the three MetS definitions and CHD and stroke.

RESULTSIn subjects without hypertension, the prevalence of Mets was 4.1% by NCEP definition, 8.3% revised NCEP definition and 7.8% IDF definition. In hypertensive individuals, the prevalence was 14.0%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by the same definitions, respectively. In hypertensive individuals, the agreement was 94.4% in men and 97.0% in women between revised NCEP and IDF definitions. The IDF defined MetS was more strongly associated with CHD than the NCEP or revised NCEP defined MetS (adjusted odds ratio: 1.92 compared with 1.85 and 1.69 in men; 1.64 compared with 1.48 and 1.60 in women).

CONCLUSIONSIn the patients with hypertension, the revised NCEP and IDF definitions identified more individuals than NCEP definition and their agreement is very high. The IDF defined MetS is more strongly associated with CHD than the NCEP or revised NCEP defined MetS, but weakly or not associated with stroke.

Adult ; Aged ; Cardiovascular Diseases ; etiology ; Coronary Disease ; etiology ; Cross-Sectional Studies ; Female ; Humans ; Hypertension ; complications ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Prevalence ; Stroke ; etiology

Previous reports suggested that a novel stimulus pattern of multi-train stimulus at low-frequency (2-Hz or 5-Hz) could induce stable long-term depression (LTD) in the CA1 area of adult rat hippocampus. In the present study, in order to determine the mechanism in LTD induced by the two novel tetanus patterns, changes in the population spikes (PS) in the hippocampal CA1 area of adult rats following the multi-train stimulus in the presence of AP5 [antagonist of N-methyl-D-aspartate receptors (NMDARs)] or MCPG [antagonist of type I/II metabotropic glutamate receptors (mGluRs)] were recorded. The results showed that both AP5 and MCPG inhibited the LTD induced by 2-Hz multi-train stimulus. The mean amplitude of population spikes (PSA) normalized to the baseline was (96.0±3.5)% after applying AP5 (n=10) and (95.7±4.1)% after applying MCPG (n=8), respectively, measured at 20 min post-tetanus. While 5-Hz multi-train tetanus failed to induce LTD in the presence of MCPG. The mean PSA was (73.6±4.4)% (n=10) and (98.2±8.9)% (n=8) in the presence of AP5 and MCPG, respectively, measured at 35 min post-tetanus. So it is suggested that LTD induced by 2-Hz multi-train tetanus involves co-activation of NMDARs and mGluRs, while LTD induced by 5-Hz multi-train tetanus is only related to activation of mGluRs.
2-Amino-5-phosphonovalerate ; pharmacology ; Animals ; CA1 Region, Hippocampal ; physiology ; Glycine ; analogs & derivatives ; pharmacology ; Long-Term Synaptic Depression ; Rats ; Receptors, Metabotropic Glutamate ; antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors

OBJECTIVETo evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

METHODSTotally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy.

RESULTSOf the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group.

CONCLUSIONThis phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.

Adult ; Aged ; Antibodies, Monoclonal ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; pathology ; therapy ; Combined Modality Therapy ; Female ; Fever ; etiology ; Humans ; Hypotension ; etiology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Quality of Life ; Radiotherapy ; adverse effects ; methods ; Receptor, Epidermal Growth Factor ; immunology ; Remission Induction

There is no unambiguous report so far on whether short reinforcing training could establish stable spatial long-term memory and how the NMDA/NR1 expression in the hippocampal formation changes after establishment of short- and long-term memory. In the present study, three spatial memory training modes of Morris water maze were used: spatial long-term memory training mode (LT group), spatial short-term memory training mode (ST group) and short reinforcing training mode (SRT group). The characteristics of those memories established by different training modes were compared. The immunofluorescence histochemical staining technique was used to observe the changes of NMDA/NR1 expression in the hippocampal formation in the three groups. The results showed that, during Morris water maze training, no significant difference was found in the mean latency and the strategies to the target between the LT and SRT groups. The examination of the memories following different trainings indicated that the mean latency and the strategies to the target as well as the times crossing the target in LT group were not significantly different from those in SRT group, except that the mean time remaining in the platform quadrant in LT group was significantly longer than that in SRT group. In addition, no significant difference in the intensity of NMDA/NR1 immunoreactivity in CA1, CA3 and dentate gyrus of the hippocampal formation was observed between the control and ST groups or between LT and SRT groups. However, the intensity of NMDA/NR1 immunoreactivity in CA1 area and dentate gyrus in both LT and SRT groups was significantly increased as compared with that in ST or the control groups. These results suggest that the short reinforcing training mode can establish long-term spatial memory, which is almost the same as that established by the long-term training mode, and that the increase of NMDA/NR1 expression in CA1 area and dentate gyrus of the hippocampal formation may be one of the mechanisms of spatial long-term memory formation.
Animals ; Hippocampus ; chemistry ; physiology ; Male ; Memory ; Memory, Short-Term ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis ; Spatial Behavior

Previous reports suggested that a low-frequency stimulus (LFS) of 1~2 Hz (600~900 pulses) induced a homosynaptic long-term depression (LTD) of synaptic efficacy in the hippocampal CA1 area of young rats (< 4-week old). However, these stimulation protocols often failed to induce LTD in the adult CA1 hippocampus. In the present study, we examined the effects of two novel tetanus patterns on LTD induction in adult rat hippocampal slices. We determined that these novel stimulation protocols induced LTD in the adult hippocampus, and that the characteristics of induced LTD were parameter-specific, including latency (period from the end of tetanus to a beginning of LTD) and the amplitude of LTD. These results suggest that LFS with certain patterns can induce LTD in the CA1 area of adult rat hippocampal slices, and that the multi-trains of 2-Hz protocol provided more effective response than the 5-Hz protocol.
Animals ; CA1 Region, Hippocampal ; physiology ; Electric Stimulation ; In Vitro Techniques ; Long-Term Synaptic Depression ; physiology ; Male ; Rats ; Rats, Sprague-Dawley

This paper presents a remote controlled multimode micro-stimulator based on the chip nRF24E1, which consists mainly of a micro-control unit (MCU) and a radio frequency (RF) transceiver. This micro-stimulator is very compact (18 mmx28 mm two layer printed circuit board) and light (5 g without battery), and can be carried on the back of a small animal to generate electrical stimuli according to the commands sent from a PC 10 meters away. The performance and effectiveness of the micro-stimulator were validated by in vitro experiments on the sciatic nerve (SN) of the frog, where action potentials (APs) as well as artifacts were observed when the SN was stimulated by the micro-stimulator. It was also shown by in vivo behavioral experiments on operant conditioned reflexes in rats which can be trained to obey auditory instruction cues by turning right or left to receive electrical stimulation ('virtual' reward) of the medial forebrain bundle (MFB) in a maze. The correct response for the rats to obey the instructions increased by three times and reached 93.5% in an average of 5 d. This micro-stimulator can not only be used for training small animals to become an 'animal robot', but also provide a new platform for behavioral and neurophysiological experiments.
Acoustic Stimulation ; Animals ; Behavior Control ; methods ; Conditioning, Operant ; physiology ; Electric Stimulation ; instrumentation ; Equipment Design ; Male ; Medial Forebrain Bundle ; physiology ; Movement ; Rats ; Rats, Sprague-Dawley ; Remote Sensing Technology ; Robotics

Synaptic ultrastructural changes after long-lasting long-term potentiation (L-LTP) induced by 2 and 100 Hz tetanus were investigated by electron microscopic and stereological approach in slices of the developing rat visual cortex (postnatal days 15~21). Both 2 and 100 Hz tetanus-induced L-LTP groups showed significant increases in synaptic interface curvature, synaptic numeric density and postsynaptic density thickness, as well as significant decreases in the cleft width, as compared with the control groups. In addition, the volume density of the active zone (AZ) was increased significantly in the 100 Hz tetanus-induced L-LTP group, but not in the 2 Hz group. The mean lateral area of individual AZ in the 100 Hz group was relatively higher than that in the 2 Hz group. These data suggest that newly formed synapses in the 100 Hz tetanus-induced L-LTP group are larger than those in the 2 Hz group and that 100 Hz tetanus might trigger reorganization or synthesis of postsynaptic cytoskeleton.
Animals ; Animals, Newborn ; Electric Stimulation ; methods ; Long-Term Potentiation ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Synapses ; ultrastructure ; Synaptic Transmission ; physiology ; Visual Cortex ; physiology ; ultrastructure