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

Different dose series of human papillomavirus vaccine in young females: a pair-wise meta-analysis and network meta-analysis from randomized controlled trials

ObjectiveTo investigate the application value of different dose of HPV vaccine in young females.Data sourcesThe following databases were searched: Cochrane Library, PubMed, Embase, Web of Science, SINOMED, and Wanfang Data, from the establishment of the database to August 1st, 2022.Study eligibility criteriaThe inclusion criterias were: healthy young women younger than 25 years old as the research object, randomized controlled study as the research type, and the efficacy and safety of single-dose, two-dose or three-dose HPV vaccines as the intervention measures and research endpoints.Study appraisal and synthesis methodsMeta-analysis was performed to analyze the protective effects of single-dose, 2-dose and 3-dose HPV vaccine series on young females.ResultsA total of eight eligible studies involving 16 publications were included. There is no difference in the immunogenicity between the 2-dose and 3-dose series within 12 months after the last dose of HPV vaccine. However, 3-dose series was better than the 2-dose series, which performed better than the single-dose vaccine, after 12 months. With respect to the prevention of HPV16/18 infection or HPV31/33/45 infection, the single-dose vaccine worked better than 2-dose or 3-dose series.ConclusionsThe present study showed that the immunogenicity of low-dose HPV vaccine was significantly less, but it reduced the risk of high-risk HPV infection. The low-dose HPV vaccine series may not offer a preventive effect on cervical lesions, though it needs to be further confirmed by additional studies

miR-300/FA2H affects gastric cancer cell proliferation and apoptosis

MicroRNA (miR/miRNA) expression disorders play a crucial role in the development of gastric cancer (GC). Increasing evidence has indicated that miRNAs participate in the process of numerous cancers. Previous research has demonstrated that miR-300 acts as a cancer-promoting factor or tumor suppressor in a number of tumors. However, to the best of our knowledge, the effects of miR-300 on GC cells remain largely unknown. The present study investigated the effects of miR-300 on GC cells and analyzed its molecular mechanism. First, reverse transcription–quantitative polymerase chain reaction showed that miR-300 expression was increased in GC tissues and cell lines, with the highest expression observed in human gastric cancer cell line AGS. Subsequent results indicated that fatty acid 2-hydroxylase (FA2H) was a target of miR-300. FA2H-plasmid inhibited AGS cell proliferation and induced apoptosis. Finally, miR-300 inhibitor reduced cell proliferation and induced apoptosis, whereby these effects were reversed by FA2H-small interfering RNA. Therefore, the data demonstrated that miR-300/FA2H might be a new potential biomarker and therapeutic target for GC treatment

Comparative Phytonutrient Analysis of Broccoli By-Products: The Potentials for Broccoli By-Product Utilization

The phytonutrient concentrations of broccoli (Brassica oleracea var. italica) florets, stems, and leaves were compared to evaluate the value of stem and leaf by-products as a source of valuable nutrients. Primary metabolites, including amino acids, organic acids, and sugars, as well as glucosinolates, carotenoids, chlorophylls, vitamins E and K, essential mineral elements, total phenolic content, antioxidant activity, and expression of glucosinolate biosynthesis and hydrolysis genes were quantified from the different broccoli tissues. Broccoli florets had higher concentrations of amino acids, glucoraphanin, and neoglucobrassicin compared to other tissues, whereas leaves were higher in carotenoids, chlorophylls, vitamins E and K, total phenolic content, and antioxidant activity. Leaves were also good sources of calcium and manganese compared to other tissues. Stems had the lowest nitrile formation from glucosinolate. Each tissue exhibited specific core gene expression profiles supporting glucosinolate metabolism, with different gene homologs expressed in florets, stems, and leaves, which suggests that tissue-specific pathways function to support primary and secondary metabolic pathways in broccoli. This comprehensive nutrient and bioactive compound profile represents a useful resource for the evaluation of broccoli by-product utilization in the human diet, and as feedstocks for bioactive compounds for industry

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

Background. Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). Materials and methods. A network pharmacology combining experimental validation was used to investigate potential mechanisms of QDD against CLI. We firstly screened the bioactive compounds with pharmacology analysis platform of the Chinese medicine system (TCMSP) and gathered the targets of QDD and CLI. Then, we constructed a compound-target network and a protein-protein interaction (PPI) network and enriched core targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. At last, we used a CLI rat model to confirm the effect and mechanism of QDD against CLI. Enzyme-linked immunosorbent assay (ELISA), western blot (WB), and real-time quantitative polymerase chain reaction (RT-qPCR) were used. Results. 48 bioactive compounds of QDD passed the virtual screening criteria, and 53 overlapping targets were identified as core targets of QDD against CLI. A compound-CLI related target network containing 94 nodes and 263 edges was constructed. KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxia-inducible factor (HIF)-1 signaling pathway. Three PPI clusters were identified and enriched in hepatitis B and tumor necrosis factor (TNF) signaling pathway, apoptosis and hepatitis B pathway, and peroxisome pathway, respectively. Animal experiment indicated that QDD decreased serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), and IL-17 and increased prothrombin time activity (PTA) level. WB and RT-qPCR analyses indicated that, compared with the model group, the expression of cysteinyl aspartate specific proteinase-9 (caspase-9) protein, caspase-3 protein, B-cell lymphoma-2 associated X protein (Bax) mRNA, and cytochrome c (Cyt c) mRNA was inhibited and the expression of B-cell lymphoma-2 (Bcl-2) mRNA was enhanced in the QDD group. Conclusions. QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. This study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically

Multifunctional CuO-Coated Mesh for Wastewater Treatment

Funding Information: T.M. and J.Z. contributed equally to this work. The authors acknowledge the National Key R&D Program of China (No. 2017YFA0207202), the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2021JM‐202 and 2019KJXX‐064), the Innovation Capability Support Program of Shaanxi (No. 2020TD‐024), the Program for Science & Technology Innovation Team of Shaanxi Province (No. 2018TD‐030) and the Fundamental Research Funds for the Central Universities (GK202002007), and the College Students’ Innovative Entrepreneurial Training Plan Program (S202010718079) for financial supports. B. Peng acknowledges the financial support from the Academy of Finland (No. 321443 and No. 328942). Publisher Copyright: © 2021 Wiley-VCH GmbHThe complex pollutants in wastewater including insoluble oils, organic dyes, and bacteria, have caused severe environmental problems, which are harmful to ecosystems and human health and are complex and difficult to achieve wastewater purification with one material or single procedure. Herein, a facile, yet environmentally benign strategy is proposed to fabricate a superhydrophilic/underwater superoleophobic CuO-coated mesh for all-in-one wastewater treatment. In this strategy, the hierarchical micro/nanostructured CuO-coated mesh is fabricated via an oxidation–dehydration process, which simultaneously endows the mesh with superwetting ability, remarkable photocatalytic degradation ability, and excellent photodynamic antibacterial activity. This CuO-coated mesh first exhibits the special underwater superoleophobicity, superior durability, reusability, and high antifouling capability, which ensures its high separation efficiency for oil/water mixtures. Then, this CuO-coated mesh is underwater superoleophobic, possessing the remarkable photocatalytic degradation performance of organic dye contaminates in water and excellent photodynamic antibacterial activities against Escherichia coli and Staphylococcus aureus under visible-light irradiation. As such, it plays a multi-role in wastewater remedy, significantly simplifying the implementation and saving the cost in practice. This work suggests a promising approach for the design of multi-functional materials in environmental remedies.Peer reviewe

Comparative Transcriptome Analysis Provides Novel Insight into Morphologic and Metabolic Changes in the Fat Body during Silkworm Metamorphosis

The fat body plays key roles in energy storage and utilization as well as biosynthetic and metabolic activities in insects. During metamorphosis from larva to pupa, the fat body undergoes dramatic changes in morphology and metabolic processes. However, the genetic basis underlying these changes has not been completely understood. In this study, the authors performed a time-course transcriptome analysis of the fat body during silkworm metamorphosis using RNA-sequencing. A total of 5217 differentially expressed genes (DEGs) were identified in the fat body at different developmental time points. DEGs involved in lipid synthesis and degradation were highly expressed at the third day of the last larval instar and during the prepupal-pupal transition, respectively. DEGs involved in the ecdysone signaling and bone morphogenetic protein (BMP) signaling pathways that modulate organ development exhibited a high expression level during the fat body remodeling process from prepupa to pupa. Intriguingly, the RNA interference-mediated knockdown of either decapentaplegic (Dpp) or protein 60A (Gbb), two DEGs involved in the BMP signaling pathway, inhibited fat body dissociation but promoted lipid mobilization, suggesting that the BMP signaling pathway not only is required for fat body remodeling, but also moderately inhibits lipid mobilization to ensure an appropriate lipid supply during the pupal-adult transition. In conclusion, the comparative transcriptome analysis provides novel insight into morphologic and metabolic changes in the fat body during silkworm metamorphosis

Highly Selective Photoelectrochemical Conversion of Carbon Dioxide to Formic Acid

Harvesting solar energy and converting excess carbon dioxide (CO₂) in the atmosphere into energetic products hold promise in addressing both problems of detrimental energy use and serious greenhouse gas effects. Catalytic activity and selectivity were the most important aspects of this investigation. Herein, an N-Fe₂O₃/TiO₂ catalyst was reported as well as the development of a customized method for regulating the catalytic properties and mechanism for CO₂ reduction. This method enabled elevated electron transfer and regulated formation of target products (formic acid and ethanol) and control of the specific product proportions. Under optimal photoelectrochemical selective conditions, the maximal rate of formic acid production reached 74896.13 nmol h^–1 cm^–2 with a selectivity of 99.89%. Such a catalyst and controlled artificial methods can ensure catalyst selectivity and activity and offer potential applications in the production of useful chemicals from CO₂ carbon feedstock

HRD effects on first-line adjuvant chemotherapy and PARPi maintenance therapy in Chinese ovarian cancer patients

Abstract Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients