Lipid profile as a novel prognostic predictor for patients with acute myeloid leukemia.

Purpose: This study investigated the relationship between serum lipid levels and clinical outcomes in acute myeloid leukemia (AML) by establishing a predictive risk classification model. Method: A total of 214 AML patients who were pathologically diagnosed and treated with standard induction chemotherapy at Sun Yat-Sen University Cancer Center were included. The patients were randomly divided into the training (n = 107) and validation (n=107) cohorts. Univariate and multivariate Cox analyses were used to assess the value of triglyceride (TG), Apolipoprotein B (Apo B), Apo Apolipoprotein A-I (Apo A-I), cholesterol (CHO), and high-density lipoprotein (HDL) as prognostic factors for AML. Results: After a series of data analyses, a five-factor model was established to divide the patients into high- and low-risk groups. Kaplan-Meier survival analysis showed that the high-risk group had a poor prognosis (P<0.05). The area under the curve of the novel model for five-year OS was 0.737. A nomogram was constructed to integrate the model with age and the 2017 ELN cytogenetic classification, with the merged model showing improved accuracy with an area under the curve of 0.987 for five-year OS. Conclusion: A novel model was constructed using a combination of the serum lipid profile and clinical characteristics of AML patients to enhance the predictive accuracy of clinical outcomes. The nomogram used the lipid profile which is routinely tested in clinical blood biochemistry and showed both specific prognostic and therapeutic potential.

Impact of prolonged use of adjuvant tocolytics after cervical cerclage on late abortion and premature delivery.

We evaluated the impact of cervical cerclage combined with one or more uterine contraction inhibitors in persistent inhibition of uterine contraction for the treatment of late abortion and premature delivery. This retrospective case series study analysed the medical data of 58 patients who underwent cervical cerclage for cervical insufficiency and simultaneously received one or more uterine contraction inhibitors (indomethacin, ritodrine, and atosiban) and magnesium sulphate at the Zibo Maternal and Child Health Hospital between January 2019 and December 2020.Patients are normal pregnancy who received cervical cerclage without complications. The rate of successful treatment was 74.14% (43/58). The prolonged gestation duration was 16.42 ± 7.84 weeks, and the average delivery gestational age was 35.91 ± 5.16 weeks. The longest duration of treatment with a uterine contraction inhibitor or inhibitors in combination or with magnesium sulphate alone was 15.34 ± 13.16 days, and nine cases developed adverse reactions. Persistent uterine contraction inhibition after cervical cerclage could prolong pregnancy and improve pregnancy outcomes.Impact statementWhat is already known on this subject? A crucial reason for treatment failure of cervical cerclage is that uterine contraction was not effectively inhibited.What do the results of this study add? Persistent inhibition of uterine contraction after cervical cerclage prolonged pregnancy duration, increased gestational age at delivery, and improved pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? This study may provide a clinical basis for prolonging gestational age, preventing late abortion and premature delivery, and improving the survival rate and quality of life of premature infants.

Comprehensive analysis of a pyroptosis-related gene signature of clinical and biological value in acute myeloid leukaemia.

Acutemyeloidleukaemia(AML) is an illness of varied origin and unpredictable prognosis. Pyroptosis, a novel class of gasdermin-mediated programmed cell death (PCD), serves a critical function in anti-leukemia. But, the correlation between pyroptosis-related genes (PRGs) and AML prognosis is undetermined. Here, we obtained the RNA profile and matched clinical information of AML patients from the TCGA and GEO databases. 6 PRGs were identified to be strongly related to AML prognosis via univariate COX analysis. Next, the LASSO regression analysis was used to develop a PRG signature for AML prognosis, which was then employed for the stratification of patients into a low- (LR) or high-risk (HR) group. Kaplan-Meier analysis revealed that the HR group, but not the LR group, had worse prognosis. In addition, ROC curve analysis revealed that our prognotic model had good predictive value. Functional enrichment analysis indicated that the immune status was remarkably different between the two risk groups. In vitro experiments demonstrated that pyroptosis serves an essential function in anti-leukemia treatment. In summary, our newly developed model has good predictive value and can offer guidance into the precise estimation of AML prognosis and targeting pyroptosis is a potential therapeutic alternative for AML.

Integrative Analysis of a Pyroptosis-Related Signature of Clinical and Biological Value in Multiple Myeloma.

Purpose: Pyroptosis is an inflammation-based programmed cell death that holds great potential as a novel cancer therapeutic target in patients with multiple myeloma (MM). However, thus far, the function of pyroptosis-related genes (PRGs) in MM and their prognostic relevance remains undetermined. Methods: The model was established by the LASSO analysis, based on the Gene Expression Omnibus (GEO) dabatase, and its efficacy was verified using two external datasets. The model's predictive ability was assessed by the Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves. Finally, a nomogram was established for clinical application. We also confirmed the validity of our model using specimens and in vitro experiments. Results: We established an 11-PRG signature profile, and verified its efficacy using two validation cohorts (VCs). In both cohorts, patients were separated into two subpopulations, according to their median risk scores (RS). Our analysis revealed that high-risk (HR) patients experienced considerably lower overall survival (OS), compared to the low-risk (LR) patients. Using functional enrichment and immune infiltration analyses, we demonstrated that the immunologic status was strongly related to RS. Furthermore, using a pyroptosis inhibitor Q-VD-OPh, we revealed that MM cell proliferation and progression was drastically suppressed and the doxorubicin (DOX)-induced apoptosis was reversed. Conclusion: Based on our analysis, pyroptosis not only serves as a measure of MM treatment efficiency and patient prognosis, but is also a possible target for anti-MM therapy.

Establishment of a prognostic ferroptosis-related gene profile in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a heterogeneous disease with a difficult to predict prognosis. Ferroptosis, an iron-induced programmed cell death, is a promising target for cancer therapy. Nevertheless, not much is known about the relationship between ferroptosis-related genes and AML prognosis. Herein, we retrieved RNA profile and corresponding clinical data of AML patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate Cox analysis was employed to identify ferroptosis-related genes significantly associated with AML prognosis. Next, the least absolute shrinkage and selection operator (LASSO) regression was employed to establish a prognostic ferroptosis-related gene profile. 12 ferroptosis-related genes were screened to generate a prognostic model, which stratified patients into a low- (LR) or high-risk (HR) group. Using Kaplan-Meier analysis, we demonstrated that the LR patients exhibited better prognosis than HR patients. Moreover, receiver operating characteristic (ROC) curve analysis confirmed that the prognostic model showed good predictability. Functional enrichment analysis indicated that the infiltration of regulatory T cells (Treg) differed vastly between the LR and HR groups. Our prognostic model can offer guidance into the accurate prediction of AML prognosis and selection of personalized therapy in clinical practice.

MiR-483 Targeted SOX3 to Suppress Glioma Cell Migration, Invasion and Promote Cell Apoptosis.

OBJECTIVE: Glioma is the most common malignant brain tumor that has high aggressiveness. The aim of this study was to investigate the potential therapeutic targets for gliomas. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to calculate the expression of miRNA and genes. The connection between the expression of miR-483 and patients' overall survival rate was evaluated using Kaplan-Meier analysis. In addition, the underlying mechanism was detected using luciferase assay. RESULTS: The expression level of miR-483 was significantly decreased in glioma tissue samples and cell lines, compared to the adjacent tissues and normal cell lines. Downregulation of miR-483 or upregulation of SOX3 was associated with overall survival of glioma patients. Additionally, overexpression of miR-483 promotes cell invasion and migration and inhibits apoptosis. In addition, miR-483 directly targeted to SOX3, and the expression of miR-483 has a negative correlation with SOX3 in glioma tissues. SOX3 reversed partial functions of miR-483 on cell migration, invasion, and promoted cell apoptosis in glioma. CONCLUSION: MiR-483 inhibited glioma cell migration, invasion, and promoted glioma cell apoptosis by targeting SOX3. MiR-483 maybe acted as a potential target for the treatment of glioma.

Neuroprotective effects of pretreatment of ginsenoside Rb1 on severe cerebral ischemia-induced injuries in aged mice: Involvement of anti-oxidant signaling.

AIM: Ginsenosides, a class of ginseng compounds of herbal medicine, have been shown to have therapeutic potential for the neuroprotection of brain damage after cerebral ischemia because of their activities including anti-oxidant and anti-inflammation. In the elderly population, aging-induced oxidative stress has been implicated in exacerbating brain injury, which might also be ameliorated by anti-oxidants, such as ginsenosides. However, this hypothesis has yet to be explored. METHODS: Here we present in vivo studies highlighting a protective function of ginsenoside Rb1, a natural steroid glycoside derivative purified from saponin of Panax ginseng, in neurological injury during aging. RESULTS: Compared with young mice, the recovery of brain damage after middle cerebral artery occlusion is significantly impaired in aged mice, whereas the long-term pretreatment with ginsenoside Rb1 through oral administration can greatly prevent the injury in a dose-dependent manner. In addition, we further explored the involvement of oxidative stress and extracellular signal-regulated kinase activation in aged mice stimulated by cerebral ischemia, both of which were found to be blocked by ginsenoside Rb1. CONCLUSIONS: These observations suggest that ginsenoside Rb1 could represent promising applications as anti-oxidants for the anti-aging treatment of neurological disorders, such as stroke, in elderly patients. Geriatr Gerontol Int 2017; 17: 338-345.

Thalidomide: features and potential significance in oral precancerous conditions and oral cancer.

BACKGROUND: Thalidomide was originally marked as a sedative and anti-emetic, but was withdrawn after severe teratogenic effects had been discovered. More recently it has been claimed to alleviate a wide range of inflammatory disorders and malignancies. Studies showed that thalidomide might play a role in the management of some oral premalignant conditions and its potential to be an adjunct in the prevention of oral cancer. AIM: The aim of this study is to summarize the characteristics and feasibility of thalidomide in the development and prevention of oral precancerosis, and to draw attentions of researchers to its therapeutic potential in oral cancer. METHODS: Databases were searched on the basis of PubMed and EMbase. Thalidomide associated with the oral lichen planus, chronic discoid lupus erythematosus (CDLE) and oral cancer were assessed. RESULTS: We have summed up the structure and pharmacokinetics of thalidomide, possible role of thalidomide in cancer prevention, as well as the recent data concerning its effects in prevention of oral premalignant conditions and potential for the treatment of oral cancer. CONCLUSIONS: Therapeutic effects of thalidomide in oral lichen planus and CDLE have been discussed by clinical trials. And increasing evidences from in vitro and in vivo experiments show that thalidomide is a promising anticancerous agent for oral cancer, which should be paid attention to. It is necessary to perform more studies and clinical trials of large sample size to clarify underlying mechanisms and demonstrate the potential roles of thalidomide in clinical routine management of oral diseases.