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BackgroundMultiple studies have confirmed the significant role of cathepsins in the development and progression of digestive system tumors. However, further investigation is needed to determine the causal relationships.MethodsWe conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from a genome-wide association study (GWAS) to assess the causal associations between nine cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z) and six types of digestive system tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract cancer (BTC), colorectal cancer (CRC), gastric carcinoma (GC), and esophageal cancer (EC). We employed the following methods including inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran’s Q, MR-PRESSO, MR-Egger intercept test and leave-one-out sensitivity analysis. The STROBE-MR checklist for the reporting of MR studies was used in this study.ResultsThe risk of HCC increased with high levels of cathepsin G (IVW: p = 0.029, odds ratio (OR) = 1.369, 95% confidence interval (CI) = 1.033-1.814). Similarly, BTC was associated with elevated cathepsin B levels (IVW: p = 0.025, OR = 1.693, 95% CI = 1.070-2.681). Conversely, a reduction in PCa risk was associated with increased cathepsin H levels (IVW: p = 0.027, OR = 0.896, 95% CI = 0.812-0.988). Lastly, high levels of cathepsin L2 were found to lower the risk of CRC (IVW: p = 0.034, OR = 0.814, 95% CI = 0.674-0.985).ConclusionOur findings confirm the causal relationship between cathepsins and digestive system tumors, which can offer valuable insights for the diagnosis and treatment of digestive system tumors.

This paper presents an ultra-wideband, low insertion loss, and high accuracy 6-bit digital step attenuator (DSA). To improve the accuracy of amplitude and phase shift of the attenuator, two innovative compensation structures are proposed in this paper: a series inductive compensation structure (SICS) designed to compensate for high frequency attenuation values and a small bit compensation structure (SBCS) intended for large attenuation bits. Additionally, we propose insertion loss reduction techniques (ILRTs) to reduce insertion loss. The fabricated 6-bit DSA core area is only 0.51 mm2, and it exhibits an attenuation range of 31.5 dB in 0.5 dB steps. Measurements reveal that the root-mean-square (RMS) attenuation and phase errors for the 64 attenuation states are within 0.18 dB and 7°, respectively. The insertion loss is better than 2.54 dB; the return loss is better than −17 dB; and the input 1 dB compression point (IP1 dB) is 29 dBm at IF 12 GHz. To the best of our knowledge, this chip presents the highest attenuation accuracy, the lowest insertion loss, the best IP1dB, and a good matching performance in the range of 2–22 GHz using the 0.25 μm GaAs p-HEMT process.