Search

While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%). No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma.

ET-743 (trabectedin, Yondelis) and PM00104 (Zalypsis) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood.Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines. We found that a large number of genes have altered expression levels in CS-1/ER and CS-1/PR when compared to the parental cell line. 595 CS-1/ER and 498 CS-1/PR genes were identified as overexpressing; 856 CS-1/ER and 874 CS-1/PR transcripts were identified as underexpressing. Three zinc finger protein (ZNF) genes were on the top 10 overexpressed genes list. These genes have not been previously associated with drug resistance in tumor cells. Differential expressions of ZNF93 and ZNF43 genes were confirmed in both CS-1/ER and CS-1/PR resistant cell lines by real-time RT-PCR. ZNF93 was overexpressed in two ET-743 resistant Ewing sarcoma cell lines as well as in a cisplatin resistant ovarian cancer cell line, but was not overexpressed in paclitaxel resistant cell lines. ZNF93 knockdown by siRNA in CS-1/ER and CS-1/PR caused increased sensitivity for ET-743, PM00104, and cisplatin. Furthermore, ZNF93 transfected CS-1 cells are relatively resistant to ET-743, PM00104 and cisplatin.This study suggests that zinc finger proteins, and ZNF93 in particular, are involved in resistance to ET-743 and PM00104.

Objectives: This meta-analysis aims to assess the association between adult nap duration and risk of all-cause mortality and cardiovascular diseases (CVD). Methods: PubMed, Cochrane Library, Embase and Web of Science databases were searched to identify eligible studies. The quality of observational studies was assessed using the Newcastle-Ottawa Scale. We performed all statistical analyses using Stata software version 14.0. For the meta-analysis, we calculated hazard ratio (HR) and their corresponding 95% confidence intervals (CIs). To assess publication bias, we used a funnel plot and Egger's test. Results: A total of 21 studies involving 371,306 participants revealed varying methodological quality, from moderate to high. Those who indulged in daytime naps faced a significantly higher mortality risk than non-nappers (HR: 1.28; 95% CI: 1.18–1.38; I2 = 38.8%; P<0.001). Napping for less than 1 hour showed no significant association with mortality (HR: 1.00; 95% CI: 0.90–1.11; I2 = 62.6%; P = 0.971). However, napping for 1 hour or more correlated with a 1.22-fold increased risk of mortality (HR: 1.22; 95% CI: 1.12–1.33; I2 = 40.0%; P<0.001). The risk of CVD associated with napping was 1.18 times higher than that of non-nappers (HR: 1.18; 95% CI: 1.02–1.38; I2 = 87.9%; P = 0.031). Napping for less than 1 hour did not significantly impact CVD risk (HR: 1.03; 95% CI: 0.87–1.12; I2 = 86.4%; P = 0.721). However, napping for 1 hour or more was linked to a 1.37-fold increased risk of CVD (HR: 1.37; 95% CI: 1.09–1.71; I2 = 68.3%; P = 0.007). Conclusions: Our meta-analysis indicates that taking a nap increases the risk of overall mortality and CVD mortality. It highlights that the long duration time of the nap can serve as a risk factor for evaluating both overall mortality and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Background: Parental feeding practices (PFPs) play a key role in fostering preschoolers' dietary habits and in mitigating the risk of childhood obesity. Nevertheless, parents often employ inappropriate feeding practices, leading to children's potential nutrition-related issues. Thus, research is needed to inform interventions that focus on optimizing feeding practices. Methods: This protocol describes the evaluation of a novel intervention—Empowering Parents to Optimize Feeding Practices (EPO-Feeding Program). The program will be evaluated with a two-arm feasibility randomized controlled trial (RCT) in Yangzhou, China. The program includes four weekly group-based training sessions led by healthcare professionals for parents of preschool children. The intervention incorporates sessions, group discussions, motivational interviewing, and supplementary materials (e.g., key messages and educational videos) aimed at enhancing parents' knowledge, skills, and behaviours related to feeding practices. The primary outcomes include i) implementation feasibility, primarily assessed through retention rates; and ii) program acceptability through a survey and qualitative process evaluation. Secondary outcomes encompass the potential impacts on i) PFPs, ii) parental perception of child weight (PPCW), iii) parenting sense of competence, iv) children's eating behaviours, and v) child weight status. Quantitative analyses include descriptive estimates for evaluating the feasibility and linear mixed regression analysis for testing the potential effects. Qualitative valuation will use thematic framework analysis. Discussion: If this study shows this program to be feasible to implement and acceptable to parents, it will be used to inform a fully powered trial to determine its effectiveness. The research will also help inform policy and practices in the context of child nutrition promotion, particularly regarding implementing group-based training sessions by healthcare providers in similar settings. Trial registration: Clinicaltrials.gov, Protocol #NCT06181773, 20/11/2023. [ABSTRACT FROM AUTHOR]

Background: Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer. Methods: The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis. Results: Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58–0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65–1.43; P = 0.85; I2 = 46%). Conclusion: In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best. [ABSTRACT FROM AUTHOR]

The implementation of tax reduction policies in China represents a significant and effective strategy. Accordingly, this strategy has been designed to facilitate the development of a green economy by establishing a market-oriented allocation system for environmental and resource elements, while simultaneously invigorating microeconomic entities. As the nation navigates towards the adoption of green, low-carbon production, and lifestyles, the role of clean and green energy emerges as a vital necessity. Therefore, to explain the impact of tax reduction policies on the green energy industry, this study collected and compiled financial indicator data from 100 listed companies in the green energy sector, utilizing the China Stock Market Accounting Research database (CSMAR) as a source for research samples. A Panel Vector Auto Regression (PVAR) model was employed to observe the effects of tax reduction policies on the energy industry, while the dosage effects Difference in Difference (DID) model was utilized to verify and supplement the findings. In summary, the findings of this study can be summarized as follows: firstly, tax reduction policies exert a positive impact on the green energy industry by effectively mitigating the financial cost burden on green energy enterprises, thereby reducing production expenses and amplifying their profitability. Secondly, such policies bolster the capital turnover rate of enterprises in the short term, thereby enabling augmented research and development investments, refining production efficiency, and enhancing competitiveness. Through rigorous analysis and demonstration, the research findings accentuate the stimulative and propulsive impacts of tax reduction policies on the flourishing development of the green energy industry. Furthermore, this study provides relevant fiscal and tax policy recommendations, thoughtfully derived from the research findings. [ABSTRACT FROM AUTHOR]

Mushrooms that are morphologically indistinguishable from Russula virescens (Schaeff.) Fr. are among the most popular wild edible mushrooms in Yunnan province, southwestern China. However, almost nothing is known about their biology. This study investigated the diversity and population genetics of a R. virescens ally from Yunnan. A total of 210 samples were collected from 13 geographical locations throughout the main distribution range in Yunnan. The patterns of genetic variation within and among these geographic populations were analyzed using sequences from three nuclear and two mitochondrial DNA fragments. Analysis of the ITS sequences revealed that samples from Yunnan showed 3–6% sequence difference from R. virescens samples from North America and Europe and formed a distinct clade. Our multilocus population genetic analyses suggested frequent gene flow among geographic populations of the R. virescens ally in Yunnan. Interestingly, the nuclear and mitochondrial genes exhibited different levels of gene flow and recombination. We discuss the implications of our results for understanding speciation, reproduction and conservation of this important biological resource. [ABSTRACT FROM AUTHOR]