Research Progress of GABA Receptors in Alzheimer’s Disease / 中国生物化学与分子生物学报

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the early symptom of A β plaque, tau hyperphosphorylation neuronal tangle formation in cells. At present, accumulated evidence shows that the changes of GABA receptors are closely related to AD. Some studies have shown that the expression level of each subunit of the GABA receptor changes in AD patients. Therefore, it is speculated that the changes of GABA subunits may be related to the pathogenesis of AD, but there is no better methods to improve AD by targeting GABA receptors. In order to further understand the relationship between the changes of GABA receptors and AD, this paper first reviewed the changes of GABA receptors in AD patients and animal models’ brains and found that there was differential expression in GABA(A) receptor subunits in AD patients. Then we summarized the changes of GABA receptor subunits in Alzheimer database. Based on the data, we found that a few GABA subunits had significant changes. The evidence shows that the change of GABA receptors alters the neural activity in the brain. Other studies have found that the treatment of mice with GABA receptor agonists and antagonists can improve the cognitive ability of mice. We hope that understanding the differential expression of GABA receptors in AD will provide a more accurate target for the treatment of AD.

Quantitative and comparative proteomics analysis in clear cell renal cell carcinoma and adjacent noncancerous tissues by 2-D DIGE / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify specific protein markers for renal cell carcinoma detection and diagnosis, as well as develop new potential therapeutic targets of the disease.</p><p><b>METHODS</b>We used two-dimensional difference in-gel electrophoresis (2-D DIGE) technique conjunction with mass spectrometry (MS) for the identification of significant differentially expressed proteins between 15cases of paired clear cell renal cell carcinoma (ccRCC) and adjacent normal renal tissues. The protein spots were considered as differentially expressed if a 1.5-fold altered expression level was observed (Student's t test, P value<0.05).</p><p><b>RESULTS</b>Of the 27 differentially expressed protein spots, 26 proteins were successfully identified. 11 proteins up-regulated in renal cell carcinoma,15 proteins down-regulated. Among them Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACDSB), Aldose 1-epimerase (GALM), Peroxiredoxin-4 (PRDX4), Macrophage-capping protein (CAPG), Beta-defensin 107 (D107A), Microfibril-associated glycoprotein 4 (MFAP4) were first time screening as new differential expressed proteins by protomic study in renal cell carcinoma.</p><p><b>CONCLUSIONS</b>2-D DIGE is a useful technique for screening and analysis differential expressed proteins in renal cell carcinoma. These new differently expressed proteins may be useful for development new molecular markers for the tumor.</p>

Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT).</p><p><b>METHODS</b>Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay.</p><p><b>RESULTS</b>Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits.</p><p><b>CONCLUSION</b>Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia.</p>

Patient outcome and prognostic factors of renal cell carcinoma in clinical stage T(1-3)N(1-2)M(0): a single-institution analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To report our data of patients with clinical stage T(1-3)N(1-2)M(0) renal cell carcinoma (RCC) and explore the biological behavior of this malignancy.</p><p><b>METHODS</b>A total of 531 patients with no distant metastatic RCC underwent open radical nephrectomy at our institution between 1988 and 2008, among whom 42 patients with histological nodal metastases had successful surgical tumor resection. The clinical data and outcomes of the 42 patients were analyzed.</p><p><b>RESULTS</b>Of those 42 patients, 19.0% had T1, 21.4% had T2, and 59.5% had T3 stage tumors; 42.9% had N1 and 57.1% had N2 stage tumors. Tumor recurred in 30 (71.4%) patients after the surgery, and death occurred in 26 (61.9%) cases at the last follow-up; among the recurrent cases, 83.3% (25/30) had multiple metastases at the initial recurrence. The median cancer-specific survival (CSS) and disease-free survival (DFS) was 23 and 11 months in these cases, respectively. Multivariate analysis demonstrated that Fuhrman grade (P=0.005), N stage (P=0.014) and T stage (P=0.037) were the independent predictors of CSS; Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P=0.002), tumor size (P=0.007), Fuhrman grade (P=0.009) and N stage (P=0.019) were the independent predictors of DFS.</p><p><b>CONCLUSION</b>Patients with T(1-3)N(1-2)M(0) RCC have poor prognosis. N stage is an independent predictor of both CSS and DFS, suggesting that extended lymph node dissection should be performed when suspicious enlarged nodal disease is found during surgery.</p>

Synchronous squamous cell carcinoma of the renal pelvis and squamous cell carcinoma of the ureter: report of two cases and review of literature / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the clinicopathological characteristics of synchronous squamous cell carcinoma (SCC) of the renal pelvis and SCC of the ureter.</p><p><b>METHODS</b>The clinical data of two cases of synchronous SCC of the renal pelvis and SCC of the ureter were retrospectively reviewed and analyzed. In case 1, a 68-year-old man with hematuria for a month, imaging modalities revealed a right renal pelvis tumor and a right distal ureter tumor. The patient underwent nephroureterectomy and excision of the bladder cuff. Case 2, a 60-year-old man with the complaint of lower abdominal pain and left flank pain for a month, was diagnosed as left distal ureteral stone in another hospital. Ureterolithotomy was performed and a ureteral tumor was found at the lower site of the stone intraoperatively. The pathological report demonstrated SCC, and the patient was transferred to our hospital for further treatment. We found a left renal mass invading the left hemicolon during surgery, and nephroureterectomy was performed with a bladder cuff excision, left hemicolon resection, and also complete lymph node dissection. Neither of patients received adjuvant radiotherapy/chemotherapy.</p><p><b>RESULTS</b>Moderately differentiated SCC was reported in both of renal pelvis and ureter in case 1 and the tumor invaded the subepithelial connective tissue in the renal pelvis and superficial muscle in the ureter. In case 2, moderately differentiated SCC of the left renal pelvis with colon metastasis and poorly differentiated SCC of the ureter was reported with two retroperitoneal lymph node metastases. The two patients died from tumor recurrence and metastasis 5 and 6 months after the surgery, respectively.</p><p><b>CONCLUSION</b>Synchronous SCC of the renal pelvis and SCC of the ureter are rare and has high likeliness of early recurrence and metastasis, often with poor prognosis.</p>

Brain structure abnormality as genetic endophenotype of schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the role of genetic factors in the brain structural variation by using magnetic resonance imaging scan in schizophrenic patients and their unaffected siblings, and to provide experimental evidence for identifying endophenotype of schizophrenia.</p><p><b>METHODS</b>The optimized voxel-based morphometry (OVBM) was used to process the brain magnetic resonance images in 15 first episode drug-naive schizophrenic patients, 19 unaffected siblings of the patients and 38 normal control subjects. The data were analyzed by using general linear model.</p><p><b>RESULTS</b>Compared to the normal control subjects, significant decreases of gray matter was observed in first episode drug-naive schizophrenia in bilateral temporal lobe, bilateral occipital lobe, left insula, left frontal lobe superior frontal gyrus and right lentiform nucleus medial globus pallidus. Significant increases of gray matter in bilateral parietal lobe, bilateral limbic lobe cingulate gyrus in patients group while compared to controls were also found. In unaffected siblings, significant decreases of gray matter was observed in the right temporal lobe, bilateral occipital lobe, left insula, and left frontal lobe precentral gyrus, and significant increases of gray matter were found in left parietal lobe and bilateral cerebellum posterior lobe. Increased gray matter in left parietal lobe precuneus was found in first episode drug-naive schizophrenia when compared with their unaffected siblings.</p><p><b>CONCLUSION</b>There were similar brain structure abnormalities between the first episode drug-naive schizophrenia and their unaffected siblings. Genetic factor may play important role in brain structural abnormality in schizophrenia, which suggested that the brain structural change might be a genetic endophenotype of schizophrenia.</p>