Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK) has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f). Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1³¹² (encoding constitutively active AMPKα1) whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1). In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

Background: Rs31489 in the cleft lip and palate transmembrane1-like gene (CLPTM1L) has been identified to be associated with lung cancer through genome-wide association studies (GWAS). However, some recent replication studies yielded inconclusive results. Thus, we undertook this study to investigate the precise effect of rs31489 on lung cancer susceptibility. Materials and Methods: A hospital-based case-control study in 1,673 Chinese subjects (611 individuals with lung cancer and 1,062 controls) and a meta-analysis among 32,199 subjects (16,364 cases and 15,835 controls) were performed in this study. Results: In our case-control study, rs31489 was inversely associated with lung cancer (AC versus CC: OR=0.68, 95%CI=0.52-0.88; additive model: OR=0.68, 95%CI=0.54-0.85; dominant model: OR=0.65, 95%CI =0.51-0.84). Stratification analysis by smoking status showed a significant association and strong genetic effect in non-smokers but not in smokers. Our metaanalysis further confirmed the association, although with significant heterogeneity contributed by study design and source of controls, as shown by stratified analysis. Sensitive and cumulative analyses both indicated robust stability of our results. In addition, there was no observable publication bias in our meta-analysis. Conclusions: Overall, the findings from our replication study and meta-analysis demonstrated that CLPTM1L gene rs31489 is significantly associated with lung cancer.

Background & Objectives:The Pr evious studies of multidetector CT (MDCT) of the lower extremities for the detection of peripheral vascular disease showed high diagnostic accuracy but were performed with older generation systems. Our study aimed at assessing the diagnostic value of 128 MDCTA compared with that of digital subtraction angiography (DSA) in the grading of focal arterial disease of lower extremity arteries on the basis of anatomic regions. Materials & Methods: Forty-two patients with peripheral arterial occlusive diseases underwent both MDCTA and DSA. Lower extremity arteries depicted at MDCTA and DSA were graded separately for the degree of stenosis into 3 anatomic regions and 33 segments. Grading by MDCTA and DSA was done independently. Homogeneity analysis was used between MDCTA and DSA measurements in each patient. The sensitivity, specificity, positive predictive value and negative predictive value for detection of stenotic lesions were calculated for all anatomic regions, with findings at DSA used as the reference standard. Results: No statistically significant difference (P>.05) between DSA and MDCTA was present in Aorto-iliac and poplitiofemoral regions while there was statistically significant difference (P<.05) in the infrapopliteal region. The Sensitivity, Specificity, Positive Predictive Value and Negative Predictive Value based on a reading of MDCTA were 84.3%, 93.8%, 89.4% and 90.6% for aorto-iliac 86.6%, 94.7%, 84.1% and 94.7% for poplitiofemoral and 95.7%, 86.1%, 85.6% and 95.9% for infra-popliteal region respectively. Conclusion: MDCTA is excellent alter native in diagnosing lower extremity arterial occlusive diseases above the knee. DSA remains better on illustrating distal runoff vessels. Key words: Digital Subtr action Angiogr aphy; Multidetector CT Angiography; Peripheral Arterial Occlusive Disease Citation: Pangeni R, Han P, Pan F, Lamsal LP, Zhang Z, Yu J , Rizal R. Assessment of occlusive disease of lower extremity arteries on the basis of anatomic region: Value of 128-slice multidetector CT angiography in comparison with digital subtraction angiography. JCMS Nepal. 2016;12(4):179-86. 180 high accuracy for detection of steno-occlusive diseases compared with DSA. 4 Its advantages over DSA includes minimal invasiveness, smaller required volume of contrast material, shorter scan time and fast data acquisition. Other advantages of MDCT angiography include three dimensional (3D) volumetric data analysis and display, visualization of mural plaque and calcium. Unlike catheter angiography, MDCTA not only depicts the vessels but also allows assessment of perfusion in adjacent organs. These advantages have led to CTA replacing DSA for diagnosis at many centers. 5 However, there is a paucity of studies comparing the 128-slice MDCTA with DSA on the basis of region of blood vessel regarding grading in lower extremity. The purpose of the present study was to evaluate the diagnostic accuracy of 128-slice MDCTA in comparison with DSA in patients with PAD depending on the region o...