Tree peony (Paeonia ostii) is an economically important ornamental plant native to China. It is also notable for its seed oil, which is abundant in unsaturated fatty acids such as α-linolenic acid (ALA). Here, we report chromosome-level genome assembly (12.28 Gb) of P. ostii. In contrast to monocots with giant genomes, tree peony does not appear to have undergone lineage-specific whole-genome duplication. Instead, explosive LTR expansion in the intergenic regions within a short period (~ two million years) may have contributed to the formation of its giga-genome. In addition, expansion of five types of histone encoding genes may have helped maintain the giga-chromosomes. Further, we conduct genome-wide association studies (GWAS) on 448 accessions and show expansion and high expression of several genes in the key nodes of fatty acid biosynthetic pathway, including SAD, FAD2 and FAD3, may function in high level of ALAs synthesis in tree peony seeds. Moreover, by comparing with cultivated tree peony (P. suffruticosa), we show that ectopic expression of class A gene AP1 and reduced expression of class C gene AG may contribute to the formation of petaloid stamens. Genomic resources reported in this study will be valuable for studying chromosome/genome evolution and tree peony breeding.
IntroductionThe balance between Th17 and Treg cells controls the immune response and is an important regulator of helper T cells acting on autoimmune diseases. Focal cerebral ischemia-reperfusion injury can induce imbalance of Th17/Treg cells in the brain and the peripheral immune system of rats. The aim of this study was to investigate the effect of salidroside (Sal) on the ratio of Th17 and Treg cells in an adult rat model of middle cerebral artery occlusion (MCAO).Material and methodsForty rats were divided into 4 groups: normal group, sham group, surgery group, and Sal group. After treatment, the neurological deficits in rats were evaluated. Peripheral blood mononuclear cells were isolated and the count of Th17 and Treg cells was detected by flow cytometry. The infarct size and expression of RORt and Foxp3 were detected in rat brain tissue. Rat spleen cells were isolated, CD4+ T cells were purified by immunomagnetic beads. Treg cells were induced by adding cytokine TGF-. Th17 cells were induced by adding cytokine IL-6. The expression of STAT-3 was inhibited by SiRNA, and the effect of Sal on the differentiation of Th17/Treg cells was analyzed. The expression levels of IL-6, TNF-, MCP-1, STAT-3 and NF--B2 proteins were examined.ResultsThe results show that MCAO can induce an imbalance of Th17 and Treg cells in peripheral blood of rats. Sal treatment can significantly reduce the neurological deficit and infarct size of MCAO rats, reverse the oxidative stress of rat brain tissue, and inhibit the apoptosis of brain cells in MCAO rats. In the brain tissue of MCAO rats, Sal could significantly inhibit the expression of IL-6, TNF-, MCP-1, STAT-3 and NF--B2. Down-regulation of STAT-3 significantly reversed the therapeutic effects of Sal treatment.ConclusionsOur results indicate that Sal can increase the tolerance of rat brain tissue to ischemia, inhibit cell apoptosis and reduce oxidative stress by targeting STAT-3.
Background: This study aimed to compare the survival outcomes of radio-chemotherapy (R-CT) and radical hysterectomy with postoperative standard therapy (RH) in stage IB1-IIA2 cervical cancer patients. Methods: Based on the large amount of diagnostic and treatment cervical cancer data in China, a real-world study and 1:1 case-control matching were used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients. Results: In this real-world study, the 5-year OS and DFS in the R-CT group (n = 8949) were lower than those in the RH group (n = 18,152). After applying the inclusion criteria, the OS and DFS in the R-CT group (n = 582) were lower than those in the RH group (n = 4308). After 1:1 case-control matching, the 5-year OS and DFS in the R-CT group (n = 535) were lower than those in the RH group (n = 535) (OS: 76.1% vs. 84.6%, p < 0.001, HR = 1.819; DFS: 75.1% vs. 81.5%, p < 0.001, HR = 1.462, respectively). Further stratification showed that for stage IB1 and IIA1 patients, the 5year OS and DFS in the R-CT group (n = 300) were lower than those in the RH group (n = 300) (OS: 78.9% vs. 87.0%, p < 0.001, HR = 2.160; DFS: 77.0% vs. 84.9%, p < 0.001, HR = 2.053, respectively). In stage IB2 and IIA2 patients, the 5year OS in the R-CT group (n = 235) was lower than that in the RH group (n = 235) (72.5% vs. 81.5%, p = 0.039; HR = 1.550), but no difference in the 5-year DFS was found between the two groups (72.6% vs. 76.9%, p = 0.151). Conclusions:Our study found that for stage IB1-IIA2 cervical cancer patients, RH offers better overall survival and disease-free survival outcomes than R-CT, however, due to the inherent biases of retrospective study, it needs to be confirmed by randomized trials. In addition, we need to further understand the quality of life of the two treatments.Trial registration: registration number: CHiCTR1800017778; International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/.
Background Current opinions on whether surgical patients with cervical cancer should undergo para-aortic lymphadenectomy at the same time are inconsistent. The present study examined differences in survival outcomes with or without para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer. Methods We retrospectively compared the survival outcomes of 8802 stage IB1-IIA2 cervical cancer patients (FIGO 2009) who underwent abdominal radical hysterectomy + pelvic lymphadenectomy (n = 8445) or abdominal radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy (n = 357) from 37 hospitals in mainland China. Results Among the 8802 patients with stage IB1-IIA2 cervical cancer, 1618 (18.38%) patients had postoperative pelvic lymph node metastases, and 37 (10.36%) patients had para-aortic lymph node metastasis. When pelvic lymph nodes had metastases, the para-aortic lymph node simultaneous metastasis rate was 30.00% (36/120). The risk of isolated para-aortic lymph node metastasis was 0.42% (1/237). There were no significant differences in the survival outcomes between the para-aortic lymph node unresected and resected groups. No differences in the survival outcomes were found before or after matching between the two groups regardless of pelvic lymph node negativity/positivity. Conclusion Para-aortic lymphadenectomy did not improve 5-year survival outcomes in surgical patients with stage IB1-IIA2 cervical cancer. Therefore, when pelvic lymph node metastasis is negative, the risk of isolated para-aortic lymph node metastasis is very low, and para-aortic lymphadenectomy is not recommended. When pelvic lymph node metastasis is positive, para-aortic lymphadenectomy should be carefully selected because of the high risk of this procedure.
Background: Current opinions on whether surgical patients with cervical cancer should undergo para-aortic lymphadenectomy at the same time are inconsistent. The present study examined differences in survival outcomes with or without para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer.Methods: We retrospectively compared the survival outcomes of 8802 cervical cancer patients with stage IB1-IIA2 (FIGO 2009) from 37 hospitals in mainland China, who underwent abdominal radical hysterectomy + pelvic lymphadenectomy (n=8445) or abdominal radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy (n=357).Results: Among the 8802 patients with stage IB1-IIA2 cervical cancer, 1618 (18.38%) patients had postoperative pelvic lymph node metastasis, and 37 (10.36%) patients had para-aortic lymph node metastasis. When pelvic lymph node metastasized, the para-aortic lymph node simultaneous metastasis rate was 30.00% (36/120). The risk of isolated para-aortic lymph node metastasis was 0.42% (1/237). There were no significant differences in the survival outcomes between the para-aortic lymph node unresected and resected groups. No differences in the survival outcomes were found before or after matching between the two groups regardless of pelvic lymph node negativity/positivity. Conclusion: Para-aortic lymphadenectomy did not improve 5-year survival outcomes in surgical patients with stage IB1-IIA2 cervical cancer. Therefore, when pelvic lymph node metastasis is negative, the risk of isolated para-aortic lymph node metastasis is very low, and para-aortic lymphadenectomy is not recommended. When pelvic lymph node metastasis is positive, para-aortic lymphadenectomy should be carefully selected because of the high risk of this procedure.
Background: Nomograms are predictive tools widely used for estimating cancer prognosis. We aimed to develop/validate a nomogram to predict the postsurgical 5-year overall survival (OS) and disease-free survival (DFS) probability for patients with stages IB1, IB2, and IIA1 cervical cancer [2018 International Federation of Gynecology and Obstetrics (FIGO 2018)]. Methods: We retrospectively enrolled cervical cancer patients at 47 hospitals with stages IB1, IB2, and IIA1 disease from the Clinical Diagnosis and Treatment for Cervical Cancer in China database. All patients were assigned to either the development or validation cohort (75% of patients used for model construction and 25% used for validation). OS and DFS were defined as the clinical endpoints. Clinicopathological variables were analyzed based on the Cox proportional hazards regression model. A nomogram was established and validated internally (with bootstrapping) and externally, and its performance was assessed according to the concordance index (C-index), receiver-operating characteristic curve, and calibration plot. Results: In total, 4,065 patients were enrolled and assigned to the development cohort (n=3,074) or validation cohort (n=991). The OS nomogram was constructed based on age, FIGO stage, stromal invasion, and lymphovascular space invasion (LVSI). The DFS nomogram was constructed based on the FIGO stage, histological type, stromal invasion, and LVSI. Both nomograms showed greater discrimination than the FIGO 2018 staging system in the development cohort [OS nomogram vs. FIGO 2018: C-index =0.69 vs. 0.61, area under the curve (AUC): 69.8 vs. 60.3; DFS nomogram vs. FIGO 2018: C-index =0.64 vs. 0.57, AUC: 62.6 vs. 56.9], and the same results were observed the definition in the validation cohort. Calibration plots demonstrated good agreement between the predicted and actual probabilities of 5-year OS/DFS in the development and validation cohorts. We stratified the patients into 3 subgroups with differences in OS/DFS.Each risk subgroup presented a distinct prognosis.^ ORCID: 0000-0002-1708-3047. Conclusions:We successfully developed a robust and powerful model for predicting 5-year OS/DFS in stages IB1, IB2, and IIA1 cervical cancer (FIGO 2018) for the first time. Internal and external validation showed that the model had great prediction performance and was superior to the currently utilized FIGO staging system.
Objective: To compare the oncological results and surgical outcomes of abdominal Q-M type B and type C2 radical hysterectomy (RH) for patients with FIGO 2018 stage IB1 cervical cancer.Methods: We retrospectively compared the oncological results and surgical outcomes of 1158 cervical cancer patients treated with Q-M type B (n=775) or type C2 (n=383) RH between January 2004 and December 2018 at 47 hospitals in mainland China.Results: The type B group and type C2 group showed similar 5-year DFS and OS rates (OS: 98.5% vs 98.0%, P=0.461; DFS: 94.3% vs 93.3%, p=0.461) in the total study population. Multivariable analysis revealed that Q-M type B RH was not associated with a worse 5-year OS rate (hazard ratio [HR]=1.493; 95% CI=0.522-4.269, P=0.455 95% CI: 0.522-4.269;p=0.455) or DFS rate (HR=1.169;95%CI: 0.650-2.101;p=0.603). Compared with type C2, type C resulted in a significantly shorter operating time (215 min vs. 188 min, P<0.001). The defecation time and atherization time were less in the type B group than in the type C2 RH group (3.04 d vs. 2.81 d, P<0.001; 10.59 d vs. 8.97 d, P<0.001). Additionally, intraoperative complications occurred with Q-M type C2 RH compared with Q-M type B RH (OR = 11.287, 95% CI= 4.667-27.300, P<0.001). Conclusion: Among cervical cancer patients with FIGO 2018 stage IB1 disease, the oncological outcomes of Q-M type B RH and Q-M type C2 RH were similar, and Q-M type B RH was associated with a shorter operation time, less intraoperative blood loss and fewer intraoperative complications. This suggests that Q-M type B RH might be an rational option for FIGO 2018 stage IB1 cervical cancer.
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