ABSTRACT
BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer, characterized by frequent mucin overexpression. MUC1 has been identified as a critical oncogene in the progression of CCA. However, the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete. AIM: To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients. METHODS: Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins, complemented by bioinformatic analyses. Subsequent validations were conducted through spatial transcriptomics and immunohistochemistry. The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm, which was further confirmed by independent cohorts and diverse data types. RESULTS: CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness. MUC5AC-high cells were found to promote CCA progression through WNT signaling. MUC5B-high cells exhibited robust cellular oxidation activities, leading to resistance against antitumoral treatments. MUC13-high cells were observed to secret chemokines, recruiting and transforming macrophages into the M2-polarized state, thereby suppressing antitumor immunity. MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils. Utilizing the expression levels of these mucins, a risk factor evaluation formula for CCA was developed and validated across multiple cohorts. CCA samples with higher risk factors exhibited stronger metastatic potential, chemotherapy resistance, and poorer prognosis. CONCLUSION: Our study elucidates the functional mechanisms through which mucins contribute to CCA development, and provides tools for risk stratification in CCA.
ABSTRACT
OBJECTIVE: To investigate the clinical efficacy and safety of 0.1% bromfenac sodium hydrate ophthalmic solution in myopia and astigmatism eyes after sub-Bowman keratomileusis (SBK) METHODS: A case control study. Number of patients with low to moderate myopia (-6.00 D ≤ spherical equivalent < -2.00 D) in the test and control groups was 17 cases (32 eyes) and 20 cases (40 eyes), respectively. Number of patients with high myopia (-11.00 D ≤ spherical equivalent < -6.00 D) in the test and control groups was 22 cases (42 eyes) and 15 cases (26 eyes) respectively. The first day after SBK, 0.1% bromfenac sodium hydrate eye drops was administrated 2 times/day in patients in the test group and continued for 10 and 14 days in low and high myopia, respectively. In the control group, 0.1% fluorometholone eye drops was used 4 times/day, then reduced gradually and continuously for 16 days. Visual acuity, computer refraction, intraocular pressure (IOP) and corneal topography examination were conducted at different postoperative period. Symptoms and related complications were recorded. Ranked data were statistically analyzed using the Wilcoxon rank sum test and quantitative data were analyzed using independent samples t-test. RESULTS: For low to moderate myopic patients, average postoperative IOP and corneal curvature K2 after one and three months in the test group were (7.84 ± 1.35) and (8.13 ± 1.75) mm Hg(1 mm Hg = 0.133 kPa), and (38.66 ± 1.68) and (38.75 ± 1.45) D, respectively; in the control group, these parameters were (9.37 ± 1.28) and (9.47 ± 1.58) mm Hg and (39.56 ± 1.58), and (39.51 ± 1.50) D, respectively. All of these data in the test group were lower than those in the control group, the differences were statistically significant (t = -2.299, -2.112, P < 0.05). There were no significant differences (P < 0.05) in postoperative uncorrected visual acuity, spherical equivalent, corneal curvature K1, astigmatism CY, IOP (after 6 months) and corneal curvature K2 (after 6 months) between the test and control group. For the high myopic patients, mean postoperative uncorrected visual acuity in the test group and control group after 3 months were 5.14 ± 0.06 and 5.09 ± 0.07, respectively. The difference was statistically significant (t = 2.517, P = 0.015). There were no significant differences in symptoms between these two groups (two-sided test P > 0.1). High IOP and obvious myopia regression were not found in all patients. CONCLUSIONS: Bromfenac sodium hydrate eye drops (0.1%) can achieve the same therapeutic effect as fluorometholone eye drops after SBK and the former is better than the later in postoperative IOP control.
