Platinum desensitization therapy and its impact on the prognosis of ovary high-grade serous adenocarcinoma: a real world-data

BackgroundTo examine the value of five-step platinum desensitization therapy in epithelial ovarian cancerMethodsA retrospective study was conducted on the high-grade serous adenocarcinoma of the ovary (HGSAO) patients who developed a platinum allergy during treatment and received desensitization therapy between January, 2016 and December, 2020. The logistic-regression was adopted to analyze the relationship between platinum desensitization therapy and prognosis in HGSAO patients.Results92 HGSAO patients were included in the study. Among these, 35 patients (38.0%) experienced mild allergic reactions, 51 (55.4%) experienced moderate allergic reactions, and 6 (6.5%) experienced severe allergic reactions. The desensitization therapy was successful in 86 patients (93.5%). Six patients had desensitization failure, of which five experienced severe allergic reactions during desensitization. The logistic-regression analysis revealed no significant correlation between platinum desensitization therapy and progression-free survival (PFS) or overall survival (OS) of patients (P < 0.05). However, the subgroup analysis demonstrated that the success or failure of platinum desensitization therapy significantly impacted the OS of patients who were platinum-sensitive recurrence. The patients who had successful desensitization therapy had a superior OS.ConclusionFive-step platinum desensitization therapy has potential application value in patients who were platinum-sensitive recurrence after first-line treatment but may bear the risk of severe allergic reactions

Optimization of Inner Dumping Uncovered Height with Partially Covered End Wall in Adjacent Surface Coal Mining Districts

In order to analyze the relationships of inner dumping with covered end wall in adjacent surface coal mining districts, a trough-shaped uncovered end wall model was put forward. A mathematical model concerning uncovered end wall height (UEWH) was established based on minimum cost method. The inner dump capacity was considered regarding its effect on UEWH. Besides, a comprehensive model was established for calculating optimal UEWH in inner dumping with partially covered end wall mode and a shifting distance optimization model based on cost compensation method for building a provisional haulage system to connect inner dump. As for case study in Huolinhe number 1 surface coal mine, research results show that optimal UEWH was 225 m between North Pit and South Pit whereas in number 3 mining district of North Open-Pit Mine it was 23.50 m when making its transition from cross mining to mining along strike. Nevertheless, due to limited inner dump capacity, inner dump height in South and North mining districts shall be appropriately increased and closed pits from earlier period shall be fully utilized to make room for inner dumping with partially uncovered end walls

Signal processing and generation of bioactive nitric oxide in a model prototissue

The design and construction of synthetic prototissues from integrated assemblies of artificial protocells is an important challenge for synthetic biology and bioengineering. Here we spatially segregate chemically communicating populations of enzyme-decorated phospholipid-enveloped polymer/DNA coacervate protocells in hydrogel modules to construct a tubular prototissue-like vessel capable of modulating the output of bioactive nitric oxide (NO). By decorating the protocells with glucose oxidase, horseradish peroxidase or catalase and arranging different modules concentrically, a glucose/hydroxyurea dual input leads to logic-gate signal processing under reaction-diffusion conditions, which results in a distinct NO output in the internal lumen of the model prototissue. The NO output is exploited to inhibit platelet activation and blood clot formation in samples of plasma and whole blood located in the internal channel of the device, thereby demonstrating proof-of-concept use of the prototissue-like vessel for anticoagulation applications. Our results highlight opportunities for the development of spatially organized synthetic prototissue modules from assemblages of artificial protocells and provide a step towards the organization of biochemical processes in integrated micro-compartmentalized media, micro-reactor technology and soft functional materials

PARP inhibitor maintenance treatment for newly diagnosed ovarian cancer patients: a real-world study from China

PurposeThis study evaluated the efficacy and safety in a real-world population of epithelial ovarian cancer (EOC) treated with poly (ADP-ribose) polymerase inhibitor (PARPi) as first-line maintenance therapy in the largest gynecologic oncology center in Western China.MethodsThis study included patients newly diagnosed EOC who received PARPi as first-line maintenance therapy in West China Second University Hospital from August 1, 2018 to September 31, 2022. The primary endpoints were progression-free survival (PFS) and safety evaluated by Common Terminology Criteria for Adverse Events Version 5.0(CTCAE 5.0). The secondary endpoints were overall survival (OS) and prognostic factors influencing the PFS of patients in real world.ResultsAmong the eligible 164 patients, 104 patients received olaparib and 60 patients received niraparib. 100 patients (61.0%) had mutations in breast cancer susceptibility gene (BRCA). 87 patients (53.0%) received primary debulking surgery (PDS) while 77 patients (47.0%) received interval debulking surgery (IDS). 94 patients (94/164, 57.3%) achieved R0 and 39 patients (23.8%) achieved R1 after PDS/IDS. 112 (68.3%) achieved complete response (CR) after first-line chemotherapy, while 49 (29.9%) achieved partial response (PR). The median follow-up time was 17.0 months (95% CI 15.6-18.4), and the median PFS has not been reached yet. Multivariate analysis demonstrated that BRCA mutations and CR/PR after platinum-based chemotherapy were independent factors associated with prolonged PFS. Hematologic toxicity was the most common grade≥3 AE. There were no incidence of myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML).ConclusionFocusing on PARPi as first-line maintenance therapy for patients with EOC, this study represented the largest single-center real-world study in China to date. Two independent factors were identified to prolong the PFS of patients: BRCA mutated type and CR/PR after primary treatment, which should be further confirmed with long-term follow-up and large sample sizes

Sensitive fluorescence detection of nucleic acids based on isothermal circular strand-displacement polymerization reaction

Here we have developed a sensitive DNA amplified detection method based on isothermal strand-displacement polymerization reaction. This method takes advantage of both the hybridization property of DNA and the strand-displacement property of polymerase. Importantly, we demonstrate that our method produces a circular polymerization reaction activated by the target, which essentially allows it to self-detect. Functionally, this DNA system consists of a hairpin fluorescence probe, a short primer and polymerase. Upon recognition and hybridization with the target ssDNA, the stem of the hairpin probe is opened, after which the opened probe anneals with the primer and triggers the polymerization reaction. During this process of the polymerization reaction, a complementary DNA is synthesized and the hybridized target is displaced. Finally, the displaced target recognizes and hybridizes with another probe, triggering the next round of polymerization reaction, reaching a target detection limit of 6.4 × 10−15 M

Serum and Adipose Tissue mRNA Levels of ATF3 and FNDC5/Irisin in Colorectal Cancer Patients With or Without Obesity

Objectives: To explore the activating transcription factor 3 (ATF3) and fibronectin type III domain-containing protein 5 (FNDC5)/irisin protein levels in serum and mRNA levels in subcutaneous and visceral white adipose tissue (sWAT and vWAT) in normal-weight (NW) and overweight/obese (OW/OB) patients with colorectal cancer (CRC).Methods: 76 CRC patients and 40 healthy controls were recruited. Serum ATF3 and irisin levels were detected by using ELISA kits, and the mRNA expression levels in sWAT and vWAT were measured by performing RT-qPCR.Results: The serum ATF3 levels were greater by 37.2%, whereas the irisin levels were lower by 23.3% in NW+CRC patients compared with those in healthy controls. CRC was independently associated with both ATF3 and irisin levels. The probability of CRC greater by 22.3-fold in individuals with high ATF3 levels compared with those with low ATF3 levels, whereas the risk of CRC in subjects with high irisin levels was lower by 78.0% compared to the risk in those with low irisin levels after adjustment for age, gender, BMI, and other biochemical parameters. Serum ATF3 and irisin could differentiate CRC patients from controls with receiver operating characteristic (ROC) curve areas of 0.745 (95% CI, 0.655–0.823) and 0.656 (95% CI, 0.561–0.743), respectively. The combination of ATF3 and irisin exhibited improved diagnosis value accuracy with ROC curve areas of 0.796 (95% CI, 0.710–0.866) as well as 72.6% sensitivity and 80.0% specificity.Conclusion: Increased ATF3 and reduced irisin levels were observed in sera from CRC patients. Individuals with high ATF3 and low irisin levels were more likely to have CRC. ATF3 and irisin represent potential diagnostic biomarkers for CRC patients