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Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes‐associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically‐related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that β1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, β1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery‐induced ECM stiffness can influence integrin–FAK–YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.

Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (OR, 3.12; 95% CI, 1.803-5.407). The LIG4 TT genotype carriers had decreased progressive motile sperm (p<0.05) and increased non-progressive motile sperm (p<0.001) compared with the CC genotype. Moreover, sperm concentration in subjects carrying the CT genotype was lower than that observed in CC carriers (p<0.05). The results revealed that the GG/CT and GA/CT combinations of genotypes increase the risk of infertility 3.5 and fourfold, respectively (p=0.021 and 0.004, respectively). This study demonstrated that there was an association between LIG4 Thr9Ile polymorphism and male infertility and suggests CT genotype as a risk factor for male infertility.

Introduction: Percutaneous nephrolithotomy (PCNL) is the recommended first-line treatment for staghorn stones. To achieve complete stone clearance, PCNL may require using multiple tracts. Objective: To evaluate outcome of PCNL in patients with staghorn calculi and its correlation with the number of tracts and stone features. Materials and Methods: One hundred consecutive patients with staghorn renal stone who underwent PCNL were included in the study. Perioperative and postoperative features were recorded. Correlation of the variables with number of tracts and stone size was assessed. Results: Mean age (±SD) was 49.6 ± 14.7 years. Our patients were ASA class I. The mean cumulative stone burden was 365.9 ± 156.5 mm². The mean number of tracts was 2.4 (range: 1–7), and stone-free rate was 83%. The stone-free rate (p = 0.026) and hospital stay (p = 0.005) correlated with stone size, but not with number of tracts. Postoperative fever correlated with stone size (p = 0.017) and number of tracts (p = 0.037). Conclusion: PCNL using multiple tracts seem to be effective and safe in treatment of staghorn calculi. Most outcome measures correlated with stone size rather than number of tracts.

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