Biomedical subjects

Gang Chen

Publications and source records attributed to Gang Chen.

At least 19 recordsLinked to original sources

PubMed2026

Molecular differences between poorly and well/moderately differentiated lung adenocarcinoma and their clinical implications.

BACKGROUND: Diagnostic and therapeutic techniques for lung adenocarcinoma (LUAD) have advanced rapidly. However, the morphology-based assessment of tumor differentiation commonly used in clinical practice has several limitations, including strong subjectivity, inability to reflect tumor heterogeneity, and limited prognostic predictive value. This study aimed to identify key genetic mutations associated with tumor differentiation features and explored their potential clinical impact of these molecular features on tumor prognosis and therapeutic response. METHODS: In this study, 196 LUAD tissue samples collected from Fujian Cancer Hospital between 2021 and 2023 were analyzed using integrated high-throughput sequencing and comprehensive bioinformatics approaches. Molecular differences between poorly differentiated tumors and moderately/well-differentiated tumors were characterized. The effects of these molecular alterations on tumor behavior and therapeutic response were examined, with the aim of exploring biomarkers associated with poor prognosis and treatment in LUAD. RESULTS: Our findings showed a significant quantitative difference in tumor mutation burden, EGFR co-mutations, patterns of co-occurrence resulting in distinct clinical outcomes. Among these alterations, mutations in LRP1B and TP53, as well as EGFR amplification, MET amplification, JAK2 deletion and CDKN2B deletion were significantly enriched in the poorly differentiated group, whereas EGFR mutations were significantly enriched in the moderately/well-differentiated group. We also identified MET amplification and LRP1B mutation as independent poor prognostic factors in LUAD. Moreover, a subset of poorly differentiated group exhibited DNA double-strand breaks possibly due to homologous recombination deficiency (HRD), along with frequent alterations of immune evasion-related genes. CONCLUSIONS: These findings provide novel insights into the molecular basis of LUAD and the development of novel targeted differentiation-related therapies and precision genome-guided treatments.

Lung adenocarcinoma (LUAD)↗

PubMed2026

Efficacy and safety of rib-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation at two different targets for primary palmar hyperhidrosis: a randomized controlled trial.

OBJECTIVES: To compare the efficacy and safety of computed tomography-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation (RFT) targeting the upper versus lateral margin of the fourth rib head for severe primary palmar hyperhidrosis (PPH). METHODS: Patients with severe PPH were randomly divided into Group U (upper margin target) and Group L (lateral margin target). Outcome measures included 1-year recurrence rate, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI), palm skin temperature, finger perfusion index (PI), compensatory hyperhidrosis and patient satisfaction. RESULTS: Both groups (n = 55 each, 110 sides) successfully underwent RFT. No preprocedural PI differences were found (p > 0.05). Immediately post-RFT, PI in Group L was significantly higher than in Group U (left p = 0.025, right p = 0.013). No significant differences in HDSS grades were observed between groups before and at 1 day, 2 weeks, 1 month and 3 months post-procedure. However, at 6 and 12 months, Group L showed significantly lower HDSS grades (left p = 0.033 and 0.016; right p = 0.039 and 0.025) and lower DLQI scores (p = 0.037 and 0.024) than Group U. Patient satisfaction did not differ within 6 months, but Group L had significantly higher satisfaction at 12 months (p = 0.036). CONCLUSIONS: Targeting the lateral margin of the fourth rib head for RFT achieved greater efficacy, better quality of life and higher patient satisfaction compared to the upper margin target.

Humans↗

PubMed2026

Multimodal Analysis Reveals Aberrant Expression of SUMO2 and Its Significant Association With Key Mechanisms of Metabolic Pathways in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. However, the role of small ubiquitin-like modifier 2 (SUMO2), a core member of the small ubiquitin-like modifier (SUMO) family, regarding its expression patterns and metabolism-related functions in HCC remains inadequately understood. METHODS: A multidimensional analytical framework was applied, integrating immunohistochemistry (153 HCC vs. 21 non-HCC samples), proteomics (159 paired samples), bulk transcriptomics (3240 HCC vs. 2267 non-HCC samples), single-cell RNA sequencing (RNA-seq) (10 HCC vs. 8 non-HCC samples), spatial transcriptomics, and external CRISPR/Cas9 functional genomics data. Systematic analyses included standardized mean difference (SMD), pathway enrichment, pseudotime trajectory inference, in silico knockout, cell-cell communication, metabolic flux scoring, immune infiltration, clinical correlation, drug sensitivity prediction, and molecular docking. RESULTS: At the protein level, immunohistochemistry (nuclear positivity) and external proteomic data collectively demonstrated consistent SUMO2 overexpression in HCC. Consistent upregulation was also observed at the mRNA level across large-scale cohorts. Single-cell RNA-seq and spatial transcriptomics localized SUMO2 enrichment to malignant hepatocytes and tumor-dominant regions. CRISPR-mediated SUMO2 knockout suppressed proliferation in multiple HCC cell lines. Mechanistically, high SUMO2 expression was significantly associated with metabolic reprogramming involving glycolysis/gluconeogenesis, pyruvate metabolism, and the tricarboxylic acid cycle. SUMO2-high malignant hepatocyte subpopulations exhibited enhanced activity of the macrophage migration inhibitory factor signaling axis and enhanced iron-sensor interactions. Further, the immune infiltration analysis revealed a negative correlation between SUMO2 expression and M1 macrophages and a positive correlation between follicular helper T cells and regulatory T cells. Clinically, elevated SUMO2 levels were found to be associated with adverse prognostic features. Furthermore, high SUMO2 expression was associated with increased sensitivity to dasatinib, and molecular docking simulations predicted potential binding between SUMO2 and dasatinib, with a Vina score of -8.5 kcal/mol. CONCLUSIONS: SUMO2 is aberrantly expressed at the protein, mRNA, single-cell, and spatial transcriptomic levels in HCC and is significantly associated with metabolic reprogramming and altered migration inhibitory factor (MIF)-mediated intercellular communication, suggesting its potential as a novel biomarker for diagnosis and treatment.

Humans↗

PubMed2026

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans↗

PubMed2026

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans↗

PubMed2026

Age-stratified associations of glycemia, blood pressure, and cholesterol with mortality in diabetes: A prospective cohort study.

BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. METHODS: In this prospective cohort study, 43,732 Chinese adults aged ≥ 40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (< 55, 55-<65, 65-<75, ≥ 75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. RESULTS: During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction < 0.05). Among participants aged < 75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged < 65 years and 160 mmHg in those aged 65-<75 years. Among those aged ≥ 75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c ≥ 9%, with a hazard ratio (HR) of 1.51 (95% confidence interval [CI]: 1.19-1.91) for all-cause mortality and a subdistribution hazard ratio (SHR) of 1.70 (95% CI: 1.23-2.36) for cardiovascular mortality, while SBP showed no significant association with any mortality outcome in this age group. Moreover, LDL-C emerged as a significant risk factor for cardiovascular mortality. Compared with participants with LDL-C < 1.8 mmol/L, those with LDL-C of 1.8-<2.6 mmol/L exhibited a significantly higher risk (SHR: 1.86; 95% CI: 1.11-3.11). Additionally, LDL-C had the largest PAF for cardiovascular mortality (9.6%) within this age group. CONCLUSIONS: The impacts of ABC factors on mortality risk vary substantially by age among adults with diabetes. In patients aged ≥ 75 years, less stringent glycemic and blood pressure targets may be appropriate, whereas lipid management remains critically important for reducing cardiovascular mortality.

Humans↗

PubMed2026

RPL32: From housekeeping gene to potential biomarker and therapeutic target in cancer and multiple system diseases.

Ribosomal protein L32 (RPL32) is a core component of the 60S ribosomal subunit and a stable reference gene. Mounting evidence shows that RPL32 is upregulated in hepatocellular carcinoma, lung cancer, breast cancer, prostate cancer, and other malignancies, correlating with poor prognosis. RPL32 promotes cancer cell proliferation, invasion, and progression partly through the MDM2-p53-autophagy axis, and its expression is regulated by promoter methylation, copy number variations, and transcription factors. RPL32 represents a promising prognostic biomarker and candidate intervention target for cancer. However, its clinical translation requires further validation regarding intervention efficacy, systemic toxicity, druggability, and companion diagnostics. This narrative review summarizes the structure, function, and regulatory mechanisms of RPL32, emphasizes its oncogenic roles and translational potential in cancer, and briefly describes its pathological implications in non-cancer diseases, providing a framework for future cancer research.

Humans↗

PubMed2026

Analysis of CYLD gene variants in 41 patients with multiple familial trichoepithelioma.

OBJECTIVE: To investigate the variants of the CYLD gene in Chinese patients with multiple familial trichoepithelioma (MFT), aiming to provide a scientific basis for genetic counseling and prenatal diagnosis, thereby creating favorable conditions for intervention treatment and improving the prognosis of patients. PATIENTS AND METHODS: Whole-exome sequencing (WES) was performed in patients from eleven families to identify candidate variants, which were subsequently confirmed by Sanger sequencing. The minigene technique was used to perform functional analyses of the variants c.2342-8C>G and c.1685-9T>G. Whole-genome sequencing (WGS) was applied in patients with negative WES results. RESULTS: All 41 patients presented with multiple papules or nodules on the nose. We identified six novel pathogenic variants and three recurrent pathogenic variants. Conversely, no gene variants were detected in four patients. The c.1685-9T>G variant caused aberrant mRNA splicing, resulting in the insertion of an 8-base intronic sequence into the mRNA and subsequent premature termination, while the variant c.2342-8C>G led to premature mRNA splicing seven bases upstream of the canonical splice site. CONCLUSIONS: This study identified six novel and three recurrent pathogenic variants in the CYLD gene among 41 patients with MFT. Comprising the largest sample size report in this field to date, this work considerably expands the mutational spectrum of the CYLD gene (currently comprising 144 variants) and carries important implications for genetic counseling.

Humans↗

PubMed2026

Genetically predicted associations between blood cell perturbation responses and bronchiectasis through immune mediation: A Mendelian Randomization study.

BACKGROUND: Bronchiectasis is a chronic airway disease characterized by persistent inflammation and structural damage, with substantial clinical and etiologic heterogeneity. Although previous studies have identified associations between blood cells and bronchiectasis, the causal relationships remain unclear. Moreover, the mechanisms underlying blood cell perturbation responses and their potential mediation by immune cells in disease progression are largely unexplored. METHODS: Two-sample Mendelian randomization (MR) analysis was used to explore genetically predicted associations among immune cell traits, blood cell perturbation response phenotypes, and bronchiectasis, based on genome-wide association study summary data. Mediation MR analysis was further applied to assess whether immune cells mediate these associations. Multiple sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed to evaluate the validity and robustness. RESULTS: Five blood cell perturbation response phenotypes and twenty-nine immune cell traits showed significant genetically predicted associations with bronchiectasis. Mediation analysis showed that natural killer (NK) cell absolute count partially mediated the causal effect between the eosinophil perturbation response and bronchiectasis, with a mediation proportion of 9.626%. CD38 on transitional B cells mediated the causal effect between the monocyte perturbation response and bronchiectasis, with a mediation proportion of 10.580%. Additionally, CD45 on NK cells played a mediating role in the association between the white blood cell perturbation response and bronchiectasis, with a mediation proportion of 10.651%. CONCLUSION: This study systematically explores genetically predicted associations between blood cell perturbation responses and bronchiectasis and highlights potential immune-mediated pathways. These exploratory findings provide novel genetic insights into the pathogenesis of bronchiectasis and identify potential therapeutic targets for future strategies.

Humans↗

PubMed2007

Carbon nanotube/poly(methyl methacrylate) (CNT/PMMA) composite electrode fabricated by in situ polymerization for microchip capillary electrophoresis.

We describe the development and application of a novel carbon nanotube/poly(methyl methacrylate) (CNT/PMMA) composite electrode as a sensitive amperometric detector of microchip capillary electrophoresis (CE). The composite electrode was fabricated by the in situ polymerization of a mixture of CNTs and prepolymerized methyl methacrylate in the microchannel of a piece of fused silica capillary under heat. The performance of this unique system was demonstrated by the separation and detection of phenolic pollutants and purines. The new CNT-based CE detector offered significantly lower operating potentials, yielded substantially enhanced signal-to-noise characteristics, and exhibited resistance to surface fouling and, hence, enhanced stability. Long-term stability and reproducibility with relative standard deviations of less than 5 % for the peak current (n=20) were also demonstrated. The simplicity and significant performance exhibited by the CNT/PMMA composite electrode indicate great promise for conventional CE, flowing-injection analysis, and other microfluidic analysis systems.

Electrochemistry↗

PubMed2007

Knock-down of P-glycoprotein reverses taxol resistance in ovarian cancer multicellular spheroids.

We previously established that multicellular ovarian cancer spheroids develop intrinsic multidrug resistance with the appearance of quiescent cell areas. p27 protein is a determinant of such resistance. However, the precise molecular basis of such resistance remains unknown. We demonstrated herein that these multicellular ovarian cancer spheroids expressed high levels of p27 and P-gp protein. Compared with monolayer cells, there is a significant increase in the resistance of spheroids cells to anticancer reagent Taxol. Antisense oligodeoxynucleotide not only mediated down-regulation of p27, but also P-gp expression in multicellular spheroids. Selective small interfering RNAs (siRNA) of P-gp with MDR1-targeted short hairpin RNAs (shRNA) expression vector sensitized the cells to Taxol. These results suggest that both p27 and P-gp can modulate Taxol sensitivity respectively, while p27 requires P-gp for its full function. Increased P-gp protein expression through p27 mediation is one of the major mechanisms of Taxol resistance in ovarian cancer multicellular spheroids.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Inhibition of lesion-induced neurogenesis impaired behavioral recovery in adult ring doves.

We have previously shown that electrolytic lesion-induced neurogenesis in the ventromedial nucleus of the hypothalamus (VMN) is significantly correlated with the recovery of courtship behavior in adult male ring doves. Here we revealed that reduction of lesion-induced neurogenesis in VMN impaired the behavioral recovery suggesting therefore a causal link between neurogenesis and behavioral recovery. Our results lend support that adult neurogenesis is latent in repair of injured brain.

Amino Acids↗

PubMed2006

Prevention of renal ischemic injury by silencing the expression of renal caspase 3 and caspase 8.

BACKGROUND: Apoptotic pathways mediated by caspases play a critical role in renal ischemia-reperfusion injury (IRI). Downregulation of the caspase cascade, using small interfering RNA (siRNA) to silence the expression of caspase 3 and caspase 8, may have substantial therapeutic potential for limiting renal injury. METHODS: IRI was induced in mice by clamping of the renal vein and artery for 25 or 35 min at 37 degrees C. Caspase 3 and caspase 8 (caspase 3/8) siRNA was administrated by hydrodynamic injection. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to analyze the gene silencing efficacy, and the therapeutic effects of siRNA were evaluated by renal function analysis, histological examination, and overall survival of mice suffering from IRI. RESULTS: In this study, we have shown, using quantitative PCR, that IRI is associated with increased levels of renal caspase 3/8 mRNA. Mice treated with caspase 3/8 siRNA showed a significant down-regulation in kidney expression of caspase 3/8 at both, transcriptional and protein levels. Kidney function in IRI was protected by siRNA therapy, as levels of blood urea nitrogen and creatinine were significantly reduced in mice treated with siRNA. Histological examination demonstrated that tissue injury caused by IRI was significantly reduced as a result of caspase 3/8 siRNA treatment. Furthermore, survival data showed that more than 70% of mice in siRNA-treated groups survived until the end of the eight-day observation period. CONCLUSION: Herein, we have demonstrated the therapeutic potential of using siRNA to knock down the expression of caspases and prevent acute renal injury.

Animals↗

PubMed2006

Protection of renal ischemia injury using combination gene silencing of complement 3 and caspase 3 genes.

BACKGROUND: Ischemia/reperfusion (I/R) injury occurs in clinical kidney transplantation, which results in graft dysfunction and rejection. It has been documented that I/R injury is associated with complement activation and renal cell apoptosis. The purpose of this study was to develop a strategy to prevent I/R injury using small interfering RNA (siRNA) that target complement 3 (C3) and caspase 3 genes. METHODS: siRNA-expression vectors were constructed to target C3 and caspase 3 genes. Gene silencing efficacy was assessed using real-time polymerase chain reaction. In vivo gene silencing was performed by hydrodynamic injection with C3 and caspase 3 siRNA. Renal I/R injury was induced through clamping the renal vein and artery for 25 min. I/R injury was evaluated using kidney histopathology, blood urea nitrogen (BUN), serum levels of creatinine, and survival. RESULTS: Effective gene silencing was first confirmed in vitro. Notably upregulated expression of C3 and caspase 3 genes was observed from 2 to 48 hr after I/R injury, which were effectively and specifically inhibited by C3 and caspase 3 siRNA. In comparison with control mice, serum levels of creatinine and BUN were also significantly decreased in C3 and caspase 3 siRNA-treated mice. Furthermore, the therapeutic effect of siRNA was assessed in a severe, lethal I/R injury experiment, in which siRNA treatment significantly reduced mortality. Tissue histopathology showed an overall reduction in injury area in siRNA-treated mice. CONCLUSIONS: This is the first demonstration that renal I/R injury can be prevented through silencing the complement gene and apoptosis gene, highlighting the potential for siRNA-based clinical therapy.

Animals↗

PubMed2006

Pretreatment of wastewater from triazine manufacturing by coagulation, electrolysis, and internal microelectrolysis.

We studied the pretreatment of concentrated wastewater from triazine manufacturing by coagulation, electrolysis, and internal microelectrolysis. Results show that coagulation by polyaluminum chloride at dosage of 0.5 g/L could remove up to 17.2% chemical oxygen demand (COD) from the wastewater. Electrolysis using iron electrode achieved 33.2% COD removal at current of 2A in 180 min, which was attributed to coagulation and oxidation of the organic contaminants in the wastewater by the radicals (OH and O) and oxidants (O2, O3, and H2O2) produced in electrochemical reactions. Internal microelectrolysis using iron chips and granular activated carbon (GAC) showed that up to 60.5% COD could be removed under the conditions of iron/GAC/wastewater volumetric ratio of 3:2:490, sparge ratio (ratio of air flow rate to volume of wastewater) of 2:490 min(-1), and reaction time of 132 h. COD reduction in internal microelectrolysis was attributed to a combination of chemical and physical processes, mainly oxidation by radicals and oxidants formed in electrochemical reactions, adsorption on, co-precipitation with, and enmeshment in ferrous and ferric hydroxides resulted from Fe2+ released during anode oxidation. The results suggest that internal microelectrolysis using iron chips and GAC is a promising, low-cost alternative for pretreating concentrated wastewater from pesticide manufacturing.

Aluminum Hydroxide↗

PubMed2006

Deletion of the intracellular domain of coxsackie and adenovirus receptor (CAR) enhances the expression of itself and boosts the efficiency of current adenovirus-mediated gene therapy in ovarian cancer cell lines in vitro.

The failure of adenovirus-mediated gene therapy often derives from the absence of coxsackie and adenovirus receptor (CAR) expression in target cells. We hypothesize that the slight up-regulation of CAR expression might boost the effect of adenovirus-mediated gene therapy in ovarian cancer. To test this hypothesis, we transfected full-length and intracellular-domain-deleted (tailless) CAR plasmids into CAR-deficient ovarian cancer cell line SKOV3. We observed significant elevations of the in vitro killing effect of Adv-TK and oncolytic adenovirus-mediated cytopathic effect (CPE) in transfected sub-clones, and tailless-transfected SKOV3 showed higher CAR expressions than full-length CAR-transfected cells. We conclude that the extracellular domain of CAR is essential for adenovirus-based gene therapy and, furthermore, that its intracellular domain might play an important role in the regulation of its own expression.

Adenoviridae Infections↗

PubMed2006

Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?

BACKGROUND: Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition with parecoxib in spontaneously hypertensive rats (SHRs) subjected to transient middle cerebral artery occlusion (tMCAo). METHODS: Sixty-four male SHRs were randomized to 90 min of intraluminal tMCAo or sham surgery. Parecoxib (10 mg/kg) or isotonic saline was administered intraperitoneally (IP) during the procedure, and twice daily thereafter. Nineteen animals were euthanized after 24 hours, and each hemisphere was examined for mRNA expression of pro-inflammatory cytokines and COX enzymes by quantitative RT-PCR. Twenty-three tMCAo animals were studied with diffusion and T2 weighted MRI within the first 24 hours, and ten of the SHRs underwent follow-up MRI six days later. Thirty-three SHRs were given 5-bromo-2'-deoxy-uridine (BrdU) twice daily on Day 4 to 7 after tMCAo. Animals were euthanized on Day 8 and the brains were studied with free-floating immunohistochemistry for activated microglia (ED-1), hippocampal granule cell BrdU incorporation, and neuronal nuclei (NeuN). Infarct volume estimation was done using the 2D nucleator and Cavalieri principle on NeuN-stained coronal brain sections. The total number of BrdU+ cells in the dentate gyrus (DG) of the hippocampus was estimated using the optical fractionator. RESULTS: We found a significant reduction in infarct volume in parecoxib treated animals one week after tMCAo (p < 0.03). Cortical ADC values in the parecoxib group were markedly less increased on Day 8 (p < 0.01). Interestingly, the parecoxib treated rats were segregated into two subgroups, suggesting a responder vs. non-responder phenomenon. We found indications of mRNA up-regulation of IL-1beta, IL-6, TNF-alpha and COX-2, whereas COX-1 remained unaffected. Hippocampal granule cell BrdU incorporation was not affected by parecoxib treatment. Presence of ED-1+ activated microglia in the hippocampus was related to an increase in BrdU uptake in the DG. CONCLUSION: IP parecoxib administration during tMCAo was neuroprotective, as evidenced by a large reduction in mean infarct volume and a lower cortical ADC increment. Increased pro-inflammatory cytokine mRNA levels and hippocampal granule cell BrdU incorporation remained unaffected.

Journal Article↗

PubMed2006

An inverse method to design RF coil arrays optimized for SENSE imaging.

A new method to design MRI RF coils that are optimized for SENSE (sensitivity encoding) imaging is introduced. In this approach, the inverse problem was solved where the surface current density distribution on a coil former was calculated to maximize the SNR(sense) within a volume of interest (VOI). For that purpose, an analytic relationship was formulated between the SNR(sense) and surface current density on the coil former. The SNR at pixel rho in a SENSE-MR image, SNR(sense,rho), is inversely proportional to the g-factor: therefore, the g-factor was formulated in terms of the B1 distribution of the coils. Then, by specifying the geometry of the desired coil former and using a finite element mesh (FEM), the surface current distribution was calculated to maximize the SNR(sense), by minimizing (1/SNR(sense)) in the VOI using a least squares procedure. A simple two-coil array was designed and built to test the method and phantom images were collected. The results show that the new coil design method yielded better uniformity and SNR in SENSE images compared to those of standard coils.

Algorithms↗