Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2–5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.
Background Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. Methods A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case–control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR–RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan–Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. Results The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P < 0.05) HR-HPV infection. However, no association was found between TLR4 polymorphisms and HR-HPV infection status. Kaplan–Meier time to HR-HPV clearance analysis demonstrated that women carrying rs187084 and rs352140 mutant genotypes take longer duration to clear HR-HPV infection compared with wild-type genotype carriers (P1 = 0.012; P2 = 0.031). Conclusion Our results suggested that TLR9 polymorphisms, but not TLR4, were associated with cervical persistent and multiple HR-HPV infections, which could be useful as a potential predictor of HR-HPV infection status.
This study investigated the interactions between different irrigation and nitrogen (N) fertilization rates and their effects on the 15N fertilizer absorption and utilization of Cabernet Sauvignon grapevines in a vineyard near Xinjiang, China. The fertilizer treatments consisted of three 15N-labeled urea nitrate fertilizer applications (191.4, 254.4, and 317.4 kg/ha). The irrigation treatments included two fractions (0.75 and 1.0) of estimated vineyard water use (ETc). The results showed that: (i) the residual amount of 15N fertilizer in the soil was mainly in the surface layer (0–20 cm), the residual fertilizer N in the surface layer accounted for 68–87% of the total residual N, the residual 15N fertilizer at different depths differed significantly, and the residual 15N was positively correlated with the amount of fertilizer applied (p < 0.05); (ii) The absorption of fertilizer N by grapevines accounted for only 12–17% of the total N absorption, and the proportion absorbed from soil N was as high as 82–87%. There was no significant difference in the amount of N absorbed between different water and fertilizer treatments; (iii) The 15N uptake under the different water and fertilizer treatments differed and was significantly higher in the roots than in other organs, followed by the fruit, the leaves, and finally, the stems. Our results provide a reference for improving the soil environment and encouraging a sustainable development of the grape industry. According to the experimental results, it was recommended that farmers adopt irrigation levels of 1.0 ETc and fertilizer application of 254.4 kg N/ha.
Aim: Toll-like receptors involved in tumor-associated inflammatory response, this study aimed to investigate the role of TLR4 and TLR9 gene polymorphisms in the risk and progression of HPV-related cervical lesions. Materials & methods: A total of 220 cervical lesion patients and 227 healthy controls were enrolled. Single-nucleotide polymorphisms were genotyped using PCR-restriction fragment length polymorphism. Results: A significantly decreased risk of cervical lesions was observed to be associated with the TLR4 rs10116253 (C), rs1927911 (T) and rs10759931 (G) mutant alleles. rs187084-rs1927911-HPV-16/18 was the best interaction model to affect cervical lesion risk. Conclusion: TLR4 rs10116253, rs1927911 and rs10759931 were potential biomarkers for cervical lesion susceptibility.
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