A neural circuit state change underlying skilled movements.

In motor neuroscience, state changes are hypothesized to time-lock neural assemblies coordinating complex movements, but evidence for this remains slender. We tested whether a discrete change from more autonomous to coherent spiking underlies skilled movement by imaging cerebellar Purkinje neuron complex spikes in mice making targeted forelimb-reaches. As mice learned the task, millimeter-scale spatiotemporally coherent spiking emerged ipsilateral to the reaching forelimb, and consistent neural synchronization became predictive of kinematic stereotypy. Before reach onset, spiking switched from more disordered to internally time-locked concerted spiking and silence. Optogenetic manipulations of cerebellar feedback to the inferior olive bi-directionally modulated neural synchronization and reaching direction. A simple model explained the reorganization of spiking during reaching as reflecting a discrete bifurcation in olivary network dynamics. These findings argue that to prepare learned movements, olivo-cerebellar circuits enter a self-regulated, synchronized state promoting motor coordination. State changes facilitating behavioral transitions may generalize across neural systems.

Cell-Type-Specific Optical Recording of Membrane Voltage Dynamics in Freely Moving Mice.

Electrophysiological field potential dynamics are of fundamental interest in basic and clinical neuroscience, but how specific cell types shape these dynamics in the live brain is poorly understood. To empower mechanistic studies, we created an optical technique, TEMPO, that records the aggregate trans-membrane voltage dynamics of genetically specified neurons in freely behaving mice. TEMPO has >10-fold greater sensitivity than prior fiber-optic techniques and attains the noise minimum set by quantum mechanical photon shot noise. After validating TEMPO's capacity to track established oscillations in the delta, theta, and gamma frequency bands, we compared the D1- and D2-dopamine-receptor-expressing striatal medium spiny neurons (MSNs), which are interspersed and electrically indistinguishable. Unexpectedly, MSN population dynamics exhibited two distinct coherent states that were commonly indiscernible in electrical recordings and involved synchronized hyperpolarizations across both MSN subtypes. Overall, TEMPO allows the deconstruction of normal and pathologic neurophysiological states into trans-membrane voltage activity patterns of specific cell types.

The function role of HIGD1A in nonalcoholic steatohepatitis from chronic hepatitis B.

BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.

Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.

Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, L-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in L-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.

Neural ensemble dynamics underlying a long-term associative memory.

The brain's ability to associate different stimuli is vital for long-term memory, but how neural ensembles encode associative memories is unknown. Here we studied how cell ensembles in the basal and lateral amygdala encode associations between conditioned and unconditioned stimuli (CS and US, respectively). Using a miniature fluorescence microscope, we tracked the Ca2+ dynamics of ensembles of amygdalar neurons during fear learning and extinction over 6 days in behaving mice. Fear conditioning induced both up- and down-regulation of individual cells' CS-evoked responses. This bi-directional plasticity mainly occurred after conditioning, and reshaped the neural ensemble representation of the CS to become more similar to the US representation. During extinction training with repetitive CS presentations, the CS representation became more distinctive without reverting to its original form. Throughout the experiments, the strength of the ensemble-encoded CS-US association predicted the level of behavioural conditioning in each mouse. These findings support a supervised learning model in which activation of the US representation guides the transformation of the CS representation.

Mechanism and Progress of Natural Products in the Treatment of NAFLD-Related Fibrosis.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disorder worldwide, with liver fibrosis (LF) serving as a pivotal juncture in NAFLD progression. Natural products have demonstrated substantial antifibrotic properties, ushering in novel avenues for NAFLD treatment. This study provides a comprehensive review of the potential of natural products as antifibrotic agents, including flavonoids, polyphenol compounds, and terpenoids, with specific emphasis on the role of Baicalin in NAFLD-associated fibrosis. Mechanistically, these natural products have exhibited the capacity to target a multitude of signaling pathways, including Hedgehog, Wnt/ß-catenin, TGF-ß1, and NF-κB. Moreover, they can augment the activities of antioxidant enzymes, inhibit pro-fibrotic factors, and diminish fibrosis markers. In conclusion, this review underscores the considerable potential of natural products in addressing NAFLD-related liver fibrosis through multifaceted mechanisms. Nonetheless, it underscores the imperative need for further clinical investigation to authenticate their effectiveness, offering invaluable insights for future therapeutic advancements in this domain.

Kilohertz two-photon brain imaging in awake mice.

Two-photon microscopy is a mainstay technique for imaging in scattering media and normally provides frame-acquisition rates of ~10-30 Hz. To track high-speed phenomena, we created a two-photon microscope with 400 illumination beams that collectively sample 95,000-211,000 µm2 areas at rates up to 1 kHz. Using this microscope, we visualized microcirculatory flow, fast venous constrictions and neuronal Ca2+ spiking with millisecond-scale timing resolution in the brains of awake mice.

Fast, in vivo voltage imaging using a red fluorescent indicator.

Genetically encoded voltage indicators (GEVIs) are emerging optical tools for acquiring brain-wide cell-type-specific functional data at unparalleled temporal resolution. To broaden the application of GEVIs in high-speed multispectral imaging, we used a high-throughput strategy to develop voltage-activated red neuronal activity monitor (VARNAM), a fusion of the fast Acetabularia opsin and the bright red fluorophore mRuby3. Imageable under the modest illumination intensities required by bright green probes (<50 mW mm-2), VARNAM is readily usable in vivo. VARNAM can be combined with blue-shifted optical tools to enable cell-type-specific all-optical electrophysiology and dual-color spike imaging in acute brain slices and live Drosophila. With enhanced sensitivity to subthreshold voltages, VARNAM resolves postsynaptic potentials in slices and cortical and hippocampal rhythms in freely behaving mice. Together, VARNAM lends a new hue to the optical toolbox, opening the door to high-speed in vivo multispectral functional imaging.

Prognosis of Pediatric Patients With Mucoepidermoid Carcinoma of the Parotid Gland.

OBJECTIVE: To summarize the prognosis of pediatric patients with mucoepidermoid carcinoma (MEC) of the parotid gland. METHODS: Pediatric patients with MEC of parotid gland who were surgically treated at the Capital Medical University School of Stomatology from 2000 to 2014 were retrospectively analyzed. Clinical characteristics, pathology reports, and operation records were reviewed and analyzed. RESULTS: In total, 33 patients with an average age of 13.2 years were enrolled. The 5-year overall survival and disease-free survival were 95.8% and 84.4%, respectively. The disease-free survival and overall survival rates were lower in the under-10 age group (75.0 versus 87.7% and 83.3% versus 100%), though no statistically significant difference was found (P = 0.279 and P = 0.075). The patients who underwent complete resection all had a good prognosis without any recurrence or death regardless of whether the cut margin was 1.0 cm, 0.5 cm, or only extracapsular. One patient experienced 3 recurrences within 18 months and eventually died of disease. CONCLUSION: Good outcomes were achieved in pediatric patients with MEC of the parotid gland. Radical resection ensured a good prognosis regardless of the extent of resection. Frequent recurrence in a short period was associated with a poor prognosis. TRIAL REGISTRATION: None.

Nodal Yield: Is it a Prognostic Factor for Head and Neck Squamous Cell Carcinoma?

PURPOSE: The prognostic value of lymph node yield (LNY) in head and neck squamous cell carcinoma (HNSCC) remains controversial. The aim of this study was to explore whether LNY influences locoregional recurrence risk and prognosis in patients with HNSCC. PATIENTS AND METHODS: This retrospective cohort study reviewed the records of 1,546 eligible patients with HNSCC who were treated at Beijing Stomatological Hospital, Capital Medical University, from July 1989 to October 2012. The predictor variable was LNY. The main outcome assessment parameters were 2-year neck recurrence rate (NRR) and 5-year disease-specific survival (DSS). All statistical analyses were performed using SPSS 19.0 for Windows. RESULTS: The mean and median LNY per neck dissection were 25.1 and 23.0, respectively. There was no significant association between LNY quartile and 2-year NRR in the pN0 (P = .397) or pN(+) (P = .335) group. Univariate analysis of the pN0 group showed no significant association between LNY and 5-year DSS (P = .676). The analysis of patients with pN(+) who underwent only selective neck dissection showed a significantly higher prognostic risk with an increased LNY (LNY <19 vs ≥34, 79.2% vs 59.4%; P = .014). Interestingly, in the comprehensive neck dissection subgroup, there was an obvious tendency for patients with a high LNY to have a better 5-year DSS than those with a low LNY (LNY <19 vs ≥34, 55.6% vs 76.4%; P = .021). Multivariate analysis showed that LNY was not an independent predictive factor for 2-year NRR or 5-year DSS. CONCLUSIONS: LNY is statistically associated with the risk of lymph node metastasis, but does not predict neck recurrence. The exact prognostic value of LNY for patients with pN(+) remains unknown, and further study is needed to validate the present findings.

Clinical Features of Non-Alcoholic Fatty Liver Disease in the Non-Lean Population.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.

Growth, nutritional status, and signs of rickets in 0-5-year-old children in a Kashin-Beck disease endemic area of Central Tibet.

UNLABELLED: In order to describe the growth of 0-5-year-old Tibetan children living in a Kashin-Beck disease (KBD) endemic rural area and to examine the relationship between anthropometric indicators and clinical signs of rickets, we analyzed the baseline data of a cohort of 668 children enrolled in a prospective program of calcium and vitamin D supplementation. Tibetan children suffer from growth retardation. Z score of weight-for-age, height-for-age, weight-for-height was below -2 in 32.5%, 27.7%, and 12.1% of the children, respectively. Clinical signs of severe rickets are highly prevalent. Underweight, stunting, and clinical rickets increases with age. Prevalence of malnutrition was higher in the presence of signs of rickets. The proportion of children with a head circumference Z score < -2 was lowest when signs of rickets were observed. CONCLUSION: Stunting and underweight are frequent and probably associated with rickets.

The role of magnetic resonance imaging in assessing the extent of tongue squamous cell carcinoma: A prospective cohort study.

PURPOSE: To assess the false-positive and false-negative MRI results in evaluating the extent of tongue squamous cell carcinoma. METHODS: A prospective cohort series of 165 patients was enrolled to assess the false-positive and false-negative MRI results in evaluating the extent of tongue squamous cell carcinoma by comparing intraoperative tumor profile images and postoperative pathological sections. The differences between two-dimensional tumor margins were analyzed using Mimics 15.0 and Geomagic Control 16.0. A paired-samples t-test was used to analyze the agreement among MRI, intraoperative and pathological findings regarding the extent of tongue tumors. Multiple linear regression analysis was used to analyze associated factors. RESULTS: The mean and maximum false-positive values of pathological specimens was 1.95±1.39 mm (95% limit of agreement (LoA) 1.70-2.14) and 3.21 mm, respectively; the false-negative value was 0.44±0.49 mm. The false-positive value of intraoperative specimens was 1.52±0.87 mm (95% LoA 1.36-1.64); the false-negative value was 0.35±0.20 mm. Tumor morphology (ulcer type) (p<0.01) and depth of invasion (DOI) (≤5 mm) (p<0.01) were significantly correlated with the false-positive values of intraoperative and pathology specimens. CONCLUSION: The false-positive values are important when judging the invasion margin of tongue cancer and forming MRI-based operative plans; the false-negative value was almost negligible.

The identify role and molecular mechanism of the MALAT1/hsa-mir-20b-5p/TXNIP axis in liver inflammation caused by CHB in patients with chronic HBV infection complicated with NAFLD.

BACKGROUND/AIMS: To identify the inflammatory damage caused by chronic hepatitis B (CHB) in patients of chronic hepatitis B virus (HBV) infection complicated with non-alcoholic fatty liver disease (NAFLD), then guiding clinicians to carry out antiviral treatment. METHODS: According to the pathological features of liver biopsy, treatment-naïve obese patients of chronic HBV infection complicated with NAFLD who had elevated alanine transaminase (ALT) were divided into CHB group and NASH group. Transcriptome chips were used to analyze the expression profiles of long non-coding RNA (lncRNA) and mRNA in liver puncture tissues from the two groups. The chip data of CHB and NASH groups were analyzed for differential expression analysis, gene function analysis, signal pathway analysis, target gene prediction and competing endogenous RNAs (ceRNA) network analysis. RESULTS: By comparing CHB group with NASH group, a total of 44 differentially expressed lncRNAs and 567 differentially expressed mRNAs were screened. GO analysis predicted that the differentially expressed mRNAs may affect monooxygenase activity and oxidoreductase activity. KEGG analysis predicted that the differentially expressed mRNAs may be related to signaling pathways involved in oxidative phosphorylation, phagosomes, and NAFLD. Differential analysis of lncRNA shown that the expression of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in CHB group was significantly upregulated. Subsequently, through target gene prediction and ceRNA network analysis, we found thioredoxin interacting protein (TXNIP), which was significantly upregulated in the CHB group and had a ceRNA relationship with MALAT1. It is predicted that there may be a ceRNA regulation relationship of MALAT1/hsa-miR- 20b-5p/TXNIP. CONCLUSION: The MALAT1/hsa-miR-20b-5p/TXNIP axis may mediate CHB-induced inflammatory damage in chronic HBV infection complicated with NAFLD, and the mechanism may be related to the activation of NLRP3 inflammatory bodies and downstream inflammatory responses.

Serum SCCA, Cyfra 21-1, EGFR and Cyclin D1 levels in patients with oral squamous cell carcinoma.

OBJECTIVES: To determine the concentrations of SCCA, Cyfra 21-1, EGFR and Cyclin D1 in serum of patients with oral squamous cell carcinoma, and investigate their diagnostic value and their relationship with clinical stage, histological differentiation and lymph node metastasis. METHODS: Seventy hospitalized patients with oral squamous cell carcinoma and 72 healthy individuals were included in the study. Venous blood was collected from all study participants, in the oral carcinoma patients before tumor resection. One week after surgery, venous blood was collected again from 20 patients. Serum marker levels were determined by enzymelinked immunosorbent assay (ELISA). RESULTS: The serum SCCA, EGFR and Cyclin D1 concentrations were significantly higher in patients with oral squamous cell carcinoma than in healthy controls, while there was no significant difference in Cyfra 21-1 levels between patients and controls. The serum SCCA concentration decreased after surgery, but there was no significant difference in the serum Cyfra 21-1, EGFR and Cyclin D1 concentrations before and after surgery. Serum SCCA, Cyfra 21-1, EGFR and Cyclin D1 concentrations were not correlated with clinical stage, histological differentiation and lymph node metastasis. When SCCA, EGFR and Cyclin D1 were measured separately, EGFR had the highest diagnostic sensitivity and accuracy and Cyclin D1 had the highest specificity; when any two of the markers were tested in combination, the combined detection of EGFR and Cyclin D1 had the highest sensitivity, specificity and accuracy. CONCLUSIONS: SCCA, EGFR and Cyclin D1 may prove to be useful tumor markers in oral squamous cell carcinoma. The combined determination of EGFR and Cyclin D1 may be of value in the diagnosis of oral squamous cell carcinoma. Serum SCCA may be used as an adjunct in monitoring treatment response.

[The analysis of follow-up results of 612 cases of cholecystolithiasis treated with the minimal invasive operation with gallbladder preserved via choledochoscopy].

OBJECTIVE: To discuss the feasibility of the operation of minimal invasive with gallbladder preserved via choledochoscopy. METHODS: From February 1992 to June 2006, there were 760 patients who underwent cholecystolithiasis treated with the minimal invasive operation with gallbladder preserved via choledochoscopy, among which there were 428 males and 332 females, aged from 18 to 81 years old. All cases were diagnosed by ultrasonography and their gallbladder functions were proved normal by the examination of oral cholecystography or ECT before operation. In the operation gallstones were removed from gallbladder completely. RESULTS: There were 612 cases who were followed up for 1-15 years and the follow-up rate was 80.5%. All patients recovered well after operation. The post-operation rate of recurrence of gallstone was 0.49%, 4.39%, 5.83%, 6.60%, 7.21% and 8.38% within the first year, the second year, the third year, the fifth year, the seventh year and the ninth year respectively, rate of recurrence of gallstone were 10.11% within both the tenth and the fifteenth year. CONCLUSIONS: The minimal invasive operation with gallbladder preserved via choledochoscopy is effective to cholecystolithiasis patients whose gallbladder function is normal. It is a feasible operation that preserves the normal functional gallbladder and improves the patients' life quality.

Accuracy of magnetic resonance imaging in evaluating the depth of invasion of tongue cancer. A prospective cohort study.

OBJECTIVES: This study compared the consistency of depth of invasion (DOI) measurements by magnetic resonance imaging (MRI) and intraoperative and postoperative pathological sections due to a lack of large sample studies. MATERIALS AND METHODS: From April 2015 to December 2017, patients with squamous cell carcinoma of the tongue were included in the study. Different invasion depths were measured by MRI and on intraoperative and postoperative pathological sections. The differences between two-dimensional tumor margins were analyzed using Mimics 15.0 and Geomagic Control 16.0. Statistical analyses were performed using IBM SPSS software version 25.0 (IBM Corp., Armonk, NY). RESULTS: This study included 150 patients, the overall difference between MRI and postoperative pathological sections (DMP) and the overall difference between intraoperative and postoperative pathological sections (DIP) based on pathological specimens were 2.32 ±â€¯1.68 mm and 0.68 ±â€¯0.99 mm. The overall difference between MRI and intraoperative pathological sections (DMI) based on intraoperative specimens was 1.64 ±â€¯1.32 mm. The tumor growth pattern and T stage were significantly correlated with measurement differences. The cutoff value of MRI depth that could identify nodal metastasis was 8 mm, and were both 11 mm for OS and DSS. CONCLUSION: Clinicians performing T staging on patients with tongue cancer based on MRI measurements must consider the false-positive mean depth of 2.3 mm as well as the growth pattern and specific infiltration depth. The prognostic MRI depths that enabled the identification of nodal metastasis, OS and DSS were 8 mm, 11 mm and 11 mm, respectively. CLINICAL TRIAL REGISTRATION: Name: A Prospective, Observational, Real-world Study Based on the Register System of Oral and Maxillofacial Malignant Tumors. (ClinicalTrials.gov ID: NCT02395367).

Benzo (a) pyrene induced tumorigenesity of human immortalized oral epithelial cells: transcription profiling.

BACKGROUND: The present study was designed to examine and analyze the global gene expression changes during the tumorigenesis of a human immortalized oral epithelial cell line, and search for the possible genes that may play a role in the carcinogenesis of oral cancer associated with benzo (a) pyrene. METHODS: The human immortalized oral epithelial cells, which have been established through transfection of E6/E7 genes of human papillomavirus type 16 and proved to be non-tumorigenic in nude mice, were treated with benzo (a) pyrene. Tumorigenicity of the treated cells were examined through nude mice subcutaneous injection. The global gene expression profiles of immortalized cells and the tumorigenic cells were acquired through hybridization of a microarray of Affymetrix U133 plus 2.0. The data were analyzed using Spring 7.0 software and treated statistically using one-way analysis of variance (ANOVA). The differentially expressed genes were classified using a Venn diagram and annotated with gene ontology. Several highlighted genes were validated in cells using a real-time polymerase chain reaction. RESULTS: There were 883 differentially expressed genes during the tumorigenesis and most of them changed expression in the early stage of tumorigenesis. These genes mainly involved in macromolecule metabolism and signal transduction, possessed the molecular function of transition metal ion binding, nucleotide binding and kinase activity; their protein products were mainly integral to membranes or localized in the nucleus and cytoskeleton. The expression patterns of IGFBP3, S100A8, MAP2K, KRT6B, GDF15, MET were validated in cells using a real-time polymerase chain reaction; the expression of IGFBP3 was further validated in clinical oral cancer specimens. CONCLUSIONS: This study provides the global transcription profiling associated with the tumorigenesis of oral epithelial cells exposed to benzo (a) pyrene; IGFBP3 may play a potential role in the initiation of oral cancer related to benzo (a) pyrene exposure.

Non-invasive imaging of firefly luciferase reporter gene expression using bioluminescence imaging in human prostate cancer models.

Monitoring the expression of therapeutic genes in targeted tissues in disease models is important to assess the effectiveness and safety of systems of gene therapy delivery. In the present study, we employed a CCD (charge-coupled-device) imaging system to monitor how a prostate-specific adenovirus vector (AdPSA-Luc) mediated the long-term, sustained expression of firefly luciferase (Luc) in living human prostate cancer mouse models. The in vivo bioluminescence imaging revealed significantly high levels of luciferase expression up to 1 month, not only in prostate tumours, but also in lungs after intratumoural injection. Systemic tail vein injection of AdPSA-Luc revealed significant luciferase expression in lungs of both human prostate cancer mouse models and naïve mice, but significantly higher in the former, while the control virus, AdCMV-Luc, containing CMV (cytomegalovirus) promoter and luciferase gene, just restricted expression in the livers. Our findings demonstrate the ability of the cooled CCD camera to sensitively and non-invasively track the location, magnitude and persistence of luciferase gene expression in human prostate cancer mouse models. Monitoring of gene therapy studies in small animals may be aided considerably with further extensions of this technique.

Clinicopathological features, management and outcome of patients with poorly-differentiated oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to explore the clinicopathological features, risk factors, and management of poorly differentiated oral and oropharyngeal squamous cell carcinoma (OOSCC) patients in the northern Chinese population. METHOD: A total of 118 poorly differentiated OOSCC patients from 2236 consecutive cases were retrospectively enrolled in this study. RESULTS: Cox regression analysis showed that site (hazard ratio (HR): 2.561, 95% confidence interval (CI): 1.064-6.164, p = 0.036) and lymph node ratio (LNR) (HR: 3.915, 95% CI: 1.797-8.530, p = 0.001) were independent predictive factors for 5-year disease-specific survival (DSS). LNR >0.036, oropharynx site, and advanced clinical stage formulate a model of risk stratification. The patients with a risk score of ≥2 were identified as the high-risk population, and patients with a risk score of 0 or 1 were identified as the low-risk population. Patients in the high-risk population who underwent surgery plus concurrent chemoradiotherapy (CCRT) had markedly better 5-year DSS than those who only underwent surgery (60.0% vs. 20.0%, p = 0.016). However, patients in the low-risk population who underwent surgery alone exhibited a similar 5-year DSS (68.2%) compared with those who received surgery plus radiotherapy (RT) (68.2%) or surgery plus CCRT (50.0%) (p = 0.907). CONCLUSIONS: High LNR, oropharynx site and advanced clinical stage constitute a model of risk stratification for patients with poorly differentiated OOSCC. If two or more risk factors are present, surgery and adjuvant chemoradiotherapy can give the best prognosis.