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Objective: To evaluate the long‐term safety and effectiveness of inside–out transobturator tape (tension‐free vaginal tape‐obturator, TVT‐O) for the treatment of stress urinary incontinence (SUI). Patients and Methods: Between August 2004 and August 2006, 87 consecutive patients with SUI who underwent TVT‐O were enrolled in this prospective cohort study. Patients with mixed UI, or pelvic organ prolapse requiring surgery, were excluded. Data relating to long‐term postoperative complications, subjective satisfaction rate (Patient Global Impression of Improvement), objective cure rate (stress test), quality of life (QoL), and sexual function, were collected during follow‐up. The Incontinence Impact Questionnaire (IIQ‐7) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ‐12) were used to assess QoL and sexual function, respectively. Statistical analyses were performed using paired‐sample t‐tests. Results: At the 12‐year follow‐up, 73 patients (84%) were available for evaluation. Overall, the long‐term complication rate was 45.2%. De novo overactive bladder was observed in 12.3% of patients. None of the patients reported severe voiding dysfunction that required treatment by tape removal or catheterisation. However, 16 patients (16/73, 21.9%) had voiding changes compared with their preoperative status. Persistent groin pain was reported in 1.4% of the patients, and tape exposure occurred in 5.5%. The subjective satisfaction rate and objective cure rate were 80.8% and 82.2%, respectively. Compared with preoperative scores, the IIQ‐7 score decreased significantly (P < 0.05), whilst there was no significant difference in the PISQ‐12 score (P = 0.893). Conclusions: This 12‐year follow‐up study showed that TVT‐O is a highly effective procedure for the treatment of SUI. The long‐term complication rate appears to be slightly high, which should raise concern. [ABSTRACT FROM AUTHOR]

Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5 mg/mL LBP, 10 μΜ OXA) group ( p < 0.05). Cells in the LBP + OXA (2.5 mg/mL LBP, 10 μΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 ( p < 0.05), while it was found to upregulate Bax ( p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment ( p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups ( p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels ( p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT ( p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Ai, Xiao, Wang, Shi, Bai, Zhu and Ma.)