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1.
J Dev Biol ; 12(3)2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39311119

ABSTRACT

The NR2F family, including NR2F1, NR2F2, and NR2F6, belongs to the nuclear receptor superfamily. NR2F family members function as transcription factors and play essential roles in the development of multiple organs or tissues in mammals, including the central nervous system, veins and arteries, kidneys, uterus, and vasculature. In the central nervous system, NR2F1/2 coordinate with each other to regulate the development of specific brain subregions or cell types. In addition, NR2F family members are associated with various cancers, such as prostate cancer, breast cancer, and esophageal cancer. Nonetheless, the roles of the NR2F family in the development and diseases of the lung have not been systematically summarized. In this review, we mainly focus on the lung, including recent findings regarding the roles of the NR2F family in development, physiological function, and cancer.

2.
EMBO Rep ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39242776

ABSTRACT

Despite the efficacy of highly active antiretroviral therapy in controlling the incidence and mortality of AIDS, effective interventions for HIV-1-induced neurological damage and cognitive impairment remain elusive. In this study, we found that HIV-1 infection can induce proteolytic cleavage and aberrant aggregation of TAR DNA-binding protein 43 (TDP-43), a pathological protein associated with various severe neurological disorders. The HIV-1 accessory protein Vpu was found to be responsible for the cleavage of TDP-43, as ectopic expression of Vpu alone was sufficient to induce TDP-43 cleavage, whereas HIV-1 lacking Vpu failed to cleave TDP-43. Mechanistically, the cleavage of TDP-43 at Asp89 by HIV-1 relies on Vpu-mediated activation of Caspase 3, and pharmacological inhibition of Caspase 3 activity effectively suppressed the HIV-1-induced aggregation and neurotoxicity of TDP-43. Overall, these results suggest that TDP-43 is a conserved host target of HIV-1 Vpu and provide evidence for the involvement of TDP-43 dysregulation in the neural pathogenesis of HIV-1.

3.
Eur J Obstet Gynecol Reprod Biol ; 302: 177-183, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39288504

ABSTRACT

INTRODUCTION: This systematic review and meta-analysis aimed to describe the oncological and reproductive outcomes of patients with MSI-H/MMRd endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. METHODS: The study protocol was registered with the PROSPERO database (No: CRD42024530406). A systematic literature search in major electronic databases (PubMed, Embase, and Cochrane Library) was conducted from January 1, 2013 to August 10, 2024. The primary outcomes were complete remission (CR) rate and recurrence rate. Other outcomes included oncological outcomes in patients with Lynch syndrome and overall patient fertility status. RESULTS: The study included ten retrospective studies summarizing 66 patients with MSI-H/MMRd undergoing fertility-sparing treatment. The publication bias analysis was low. The length of follow-up varied from 3 to 164 months according to the different studies analyzed. After fertility-sparing treatment, 61.8 % of patients achieved CR, and 41.2 % of patients relapsed. Twelve patients were identified with germline mutations in Lynch syndrome, nine (75 %) achieved CR, and seven (77.8 %) relapsed. Only one study with active use of assisted reproductive technology reported a 1-year cumulative pregnancy rate of more than 60 % and more than half live births, while the remaining five studies assessed fertility outcomes and reported only one live birth. CONCLUSION: EC and AEH patients with the MSI-H/MMRd subtype had a low remission rate and high recurrence rate compared to conservative treatment. Caution is recommended when evaluating fertility-sparing therapy for patients with the MSI-H/MMRd subtype.

4.
Genes Dis ; 11(6): 101142, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39281837

ABSTRACT

Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma, representing a global health problem for which a functional cure is difficult to achieve. The HBV core protein (HBc) is essential for multiple steps in the viral life cycle. It is the building block of the nucleocapsid in which viral DNA reverse transcription occurs, and its mediation role in viral-host cell interactions is critical to HBV infection persistence. However, systematic studies targeting HBc-interacting proteins remain lacking. Here, we combined HBc with the APEX2 to systematically identify HBc-related host proteins in living cells. Using functional screening, we confirmed that proteasome activator subunit 1 (PSME1) is a potent HBV-associated host factor. PSME1 expression was up-regulated upon HBV infection, and the protein level of HBc decreased after PSME1 knockdown. Mechanistically, the interaction between PSME1 and HBc inhibited the degradation of HBc by the 26S proteasome, thereby improving the stability of the HBc protein. Furthermore, PSME1 silencing inhibits HBV transcription in the HBV infection system. Our findings reveal an important mechanism by which PSME1 regulates HBc proteins and may facilitate the development of new antiviral therapies targeting PSME1 function.

5.
Trials ; 25(1): 578, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39223633

ABSTRACT

BACKGROUND: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. METHODS: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. ETHICS AND DISSEMINATION: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. CONCLUSIONS: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.


Subject(s)
Endometrial Hyperplasia , Endometrial Neoplasms , Fertility Preservation , Gonadotropin-Releasing Hormone , Levonorgestrel , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Humans , Female , Gonadotropin-Releasing Hormone/agonists , Endometrial Hyperplasia/drug therapy , Endometrial Hyperplasia/complications , Endometrial Neoplasms/drug therapy , Fertility Preservation/methods , Pregnancy , Levonorgestrel/administration & dosage , Levonorgestrel/adverse effects , Levonorgestrel/therapeutic use , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/adverse effects , Aromatase Inhibitors/administration & dosage , Intrauterine Devices, Medicated , Treatment Outcome , Adult , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Letrozole/administration & dosage , Letrozole/therapeutic use , China , Pregnancy Rate
6.
Biotechnol Lett ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235648

ABSTRACT

Rotifers are small, ubiquitous invertebrate animals found throughout the world and have emerged as a promising model system for studying molecular mechanisms in the fields of experimental ecology, aquatic toxicology, and geroscience. However, the lack of efficient gene expression manipulation techniques has hindered the study of rotifers. In this study, we used the L4440 plasmid with two reverse-oriented T7 promoters, along with RNase-deficient E. coli HT115, to efficiently produce dsRNA and thereby present an efficient feeding-based RNAi method in Brachionus plicatilis. We targeted Bp-Ku70 & Ku80, key proteins in the DNA double-strand breaks repair pathway, and then subjected rotifers to UV radiation. We found that the mRNA expression, fecundity, as well as survival rate diminished significantly as a result of RNAi. Overall, our results demonstrate that the feeding-based RNAi method is a simple and efficient tool for gene knockdown in B. plicatilis, advancing their use as a model organism for biological research.

7.
J Psychosom Res ; 186: 111892, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39197232

ABSTRACT

BACKGROUND: Sleep disturbances are highly prevalent in oncology and often exacerbate symptoms, leading to reduced quality of life, which in turn may further affect the tolerability and efficacy of oncological treatments. Sleep disturbance and cancer have an intimate and complicated relationship, and may be a negative predictor of cancer treatment. The present study aimed to characterize the relationship between sleep disturbance and immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Data from 171 patients with advanced NSCLC, who underwent ICI treatment between December 2020 and October 2022, were analysed in our prospective study. Sleep disturbances were evaluated according to the Pittsburgh Sleep Quality Index (PSQI), with a cut-off value of 5, to investigate the impact of sleep disturbance on the survival of patients with NSCLC and the efficacy of ICI treatment. RESULTS: The median progression-free survival (PFS) was10.4 months (9 5% confidence interval [CI]:9.84-10.97). Univariate and multivariate analyses revealed that sleep disturbance and depressive symptom predicted worse prognosis with shortened PFS. Patients who experienced sleep disturbance exhibited a significant reduction in PFS (9.2 vs. 11.8 months; HR: 1.83 [9 5% CI 1.27-2.6 5]; p = 0.001), as did those with depressive states (HR 1.5 5 [9 5% CI 1.06-2.28]; p = 0.02 5). Additionally, patients with sleep disturbance and depressive symptoms exhibited significantly lower objective response rates and disease control rates. CONCLUSION: Sleep disturbance could be a factor for prognosis in patients with advanced NSCLC undergoing first- or second-line treatment with ICIs, including shorter PFS and reduced efficacy.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Sleep Wake Disorders , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/complications , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/complications , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Middle Aged , Prospective Studies , Aged , Prognosis , Adult , Depression , Quality of Life , Progression-Free Survival , Aged, 80 and over
8.
Sci Rep ; 14(1): 19780, 2024 08 26.
Article in English | MEDLINE | ID: mdl-39187553

ABSTRACT

Gingival inflammation grade serves as a well-established index in periodontitis. The aim of this study was to develop a deep learning network utilizing a novel feature extraction method for the automatic assessment of gingival inflammation. T-distributed Stochastic Neighbor Embedding (t-SNE) was utilized for dimensionality reduction. A convolutional neural network (CNN) model based on DenseNet was developed for the identification and evaluation of gingival inflammation. To enhance the performance of the deep learning (DL) model, a novel teeth removal algorithm was implemented. Additionally, a Grad-CAM + + encoder was applied to generate heatmaps for computer visual attention analysis. The mean Intersection over Union (MIoU) for the identification of gingivitis was 0.727 ± 0.117. The accuracy rates for the five inflammatory degrees were 77.09%, 77.25%, 74.38%, 73.68% and 79.22%. The Area Under the Receiver Operating Characteristic (AUROC) values were 0.83, 0.80, 0.81, 0.81 and 0.84, respectively. The attention ratio towards gingival tissue increased from 37.73% to 62.20%, and within 8 mm of the gingival margin, it rose from 21.11% to 38.23%. On the gingiva, the overall attention ratio increased from 51.82% to 78.21%. The proposed DL model with novel feature extraction method provides high accuracy and sensitivity for identifying and grading gingival inflammation.


Subject(s)
Deep Learning , Gingivitis , Humans , Gingivitis/diagnosis , Gingivitis/pathology , Neural Networks, Computer , Gingiva/pathology , Algorithms , Female , Adult , ROC Curve , Male
9.
J Affect Disord ; 364: 49-56, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39134150

ABSTRACT

Osteoarthritis (OA) is a common degenerative disease that affects millions of individuals worldwide. OBJECTIVE: There is no conclusive epidemiological evidence regarding the relationship between OA, depression, and whole-body fat mass. In this study, we conducted a two-step Mendelian randomization analysis to determine the causal relationships between them. DESIGN: The published summary-level data are from genome-wide association studies (GWAS). Our study included 357,957 samples and 10,828,862 SNPs. Finally, the outcome GWAS data for OA came from a GWAS on the genetic architecture of OA using UK Biobank data. This study included 50,508 samples and 15,845,511 SNPs. We used five different modes of analysis, including inverse variance weighted meta-analysis (IVW), MR-Egger regression, weighted median, simple mode, and weighted mode, to explore causal relationships. RESULTS: We found a positive correlation between depression and body fat mass, with depression leading to body fat mass an increase in (IVW result: p = 3.39E-07, OR (95 % CI) =2.16 (1.61, 2.90)). We also found a positive correlation between body fat mass and OA, with body fat mass increasing the risk of OA (IVW result: p = 1.65E-33, OR (95 % CI) = 1.98 (1.77, 2.21). Body fat mass played an important role as a mediator in the causal relationship between depression and OA, with approximately 14 % of the risk of OA caused by depression being mediated by body fat mass. CONCLUSIONS: Our study offers reliable evidence that depression has a detrimental impact on the risk of OA. Future research can support these associations from improving depressed effect, including social, biological, and behavioral factors, to reduce the risk of chronic diseases such as osteoarthritis. And we identified high-risk variation of alleles which associated with OA and depression can be used to predict disease and provide a basis for clinical intervention and treatment of OA.


Subject(s)
Depression , Genome-Wide Association Study , Mendelian Randomization Analysis , Osteoarthritis , Polymorphism, Single Nucleotide , Humans , Osteoarthritis/genetics , Osteoarthritis/epidemiology , Depression/genetics , Depression/epidemiology , Adipose Tissue , Genetic Predisposition to Disease/genetics
10.
Mar Environ Res ; 201: 106689, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39154542

ABSTRACT

To assess the toxicity of Hexabromocyclododecane (HBCD), the population, individual, and cellular biochemical parameters of the rotifer Brachionus plicatilis exposed to different concentrations of HBCD were investigated. The results showed that the population growth rate, reproductive period, and offspring number in B. plicatilis significantly decreased under 324 µg/L and 648 µg/L HBCD. Antioxidant enzyme activity and mRNA expression of CAT and Mn-SOD were promoted at low concentrations (32 µg/L and 64 µg/L) and inhibited at high concentrations (324 µg/L and 648 µg/L), while MDA content accumulated continuously with increasing HBCD concentrations, indicating that HBCD induced oxidation imbalance in rotifers. Further evidence was provided by the correlation between DNA fragmentation and physiological changes. The increased intercellular concentration of Ca2+ and the expression of CaM mRNA suggested that HBCD activated pathways related to calcium signaling. In summary, the excessive production of ROS induced by HBCD was considered to be the main cause of reproductive toxicity.


Subject(s)
Hydrocarbons, Brominated , Reactive Oxygen Species , Reproduction , Rotifera , Water Pollutants, Chemical , Animals , Rotifera/drug effects , Rotifera/genetics , Reactive Oxygen Species/metabolism , Water Pollutants, Chemical/toxicity , Hydrocarbons, Brominated/toxicity , Reproduction/drug effects , Calcium Signaling/drug effects
11.
J Hazard Mater ; 478: 135530, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39159580

ABSTRACT

The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on microplastic (MP) occurrence in aquatic environments deserves an in-depth study. In this study, the occurrence of MPs and environmental flux of plastics before (2019) and during (2020 and 2021) the pandemic were comparatively investigated in various aquatic compartments in the Taihu Lake Basin in China. The field-based investigations from 2019 to 2021 for Taihu Lake have shown that, at the onset of the outbreak, the MP abundance declined at a rate of 62.3 %, but gradually recovered to the pre-pandemic level. However, the amount of plastics being released into aquatic environments showed a declining trend in 2020 and 2021 compared to those in 2019, with decrease rates of 13.7 % and 15.8 %, respectively. Characterization analysis of MP particles and source apportionment framework implied that while the contributions of tire abrasion and domestic waste to MP occurrence were depleted owing to the reduction in human activity during the pandemic, weathering and fragmentation of retained plastics contributed to the recovery of stored MPs. This study provides insights into the anthropogenic influences on MP occurrence, and supports policymakers in managing and controlling plastic contamination in large freshwater systems in the "new normal" phase.


Subject(s)
COVID-19 , Environmental Monitoring , Lakes , Microplastics , Water Pollutants, Chemical , COVID-19/epidemiology , China/epidemiology , Microplastics/analysis , Water Pollutants, Chemical/analysis , Humans , SARS-CoV-2 , Pandemics
12.
Mamm Genome ; 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180568

ABSTRACT

Neurodegenerative diseases are incurable conditions that lead to gradual and progressive deterioration of brain function in patients. With the aging population, the prevalence of these diseases is expected to increase, posing a significant economic burden on society. Imaging techniques play a crucial role in the diagnosis and monitoring of neurodegenerative diseases. This study utilized a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between different imaging-derived phenotypes (IDP) in the brain and neurodegenerative diseases. Multiple MR methods were employed to minimize bias and obtain reliable estimates of the potential causal relationship between the variable exposures of interest and the outcomes. The study found potential causal relationships between different IDPs and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and frontotemporal dementia (FTD). Specifically, the study identified potential causal relationships between 2 different types of IDPs and AD, 8 different types of IDPs and PD, 11 different types of imaging-derived phenotypes and ALS, 1 type of IDP and MS, and 1 type of IDP and FTD. This study provides new insights for the prevention, diagnosis, and treatment of neurodegenerative diseases, offering important clues for understanding the pathogenesis of these diseases and developing relevant intervention strategies.

13.
RSC Adv ; 14(35): 25695-25702, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39148755

ABSTRACT

Radioiodine (mainly 129I and 131I) is known to be dangerous nuclear waste due to its high toxicity, fast mobility and long radioactive half-life. As an emerging class of novel porous organic polymers, covalent organic frameworks (COFs) have demonstrated tremendous application potential in the field of radioactive iodine capture because of their high specific surface area and tunable pore structure. Herein, three π-conjugated pyrene-based COFs, namely PyTTA-BPDA-COF, PyTTA-BPY-COF, and PyTTA-BT-COF, have been successfully prepared and used as highly efficient adsorbents for iodine capture. The experimental results show that the three COFs displayed excellent adsorption performance, with adsorption capacity of 5.03, 4.46, and 3.97 g g-1 for PyTTA-BPDA-COF, PyTTA-BPY-COF, and PyTTA-BT-COF, respectively. Additionally, the release rate of iodine-loaded COFs in methanol solution and recyclability were also impressive, demonstrating their potential for practical applications. The mechanism investigation reveals that both imine linkage and π-conjugated structure of the COFs may contribute to their high iodine adsorption capability. This work is instructive as a guide for designing and synthesizing COFs as a solid-phase adsorbent for iodine uptake.

14.
Int J Mol Sci ; 25(16)2024 Aug 18.
Article in English | MEDLINE | ID: mdl-39201665

ABSTRACT

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1-/-) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1-/-) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1-/- mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.


Subject(s)
Capsaicin , Inflammation , Lipopolysaccharides , Mice, Inbred C57BL , Obesity , TRPV Cation Channels , Toll-Like Receptor 4 , Animals , Obesity/metabolism , Obesity/drug therapy , Capsaicin/pharmacology , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Inflammation/metabolism , Inflammation/drug therapy , Humans , Mice , Toll-Like Receptor 4/metabolism , Caco-2 Cells , Mice, Knockout , Diet, High-Fat/adverse effects , Male , Occludin/metabolism , Occludin/genetics , Zonula Occludens-1 Protein/metabolism , Zonula Occludens-1 Protein/genetics , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects
15.
Front Psychol ; 15: 1428075, 2024.
Article in English | MEDLINE | ID: mdl-39006544

ABSTRACT

Once a mass health crisis breaks out, it causes concern among whole societies. Thus, understanding the individual's behavior in response to such events is key in government crisis management. From the perspective of social influence theory, this study adopts the empirical research method to collect data information in February 2020 through online survey, with a view to comprehensively describe the individuals'conformity behavior during the COVID-19 outbreak in China. The individual's conformity behavior and new influencing factors were identified. The results revealed that affective risk perception, cognitive risk perception, and individual risk knowledge had a positive significant impact on normative influence. Affective risk perception and individual risk knowledge had a positive significant on informative influence. Cognitive risk perception did not significantly impact informative influence. Informative influence and normative influence had a positive effect on conformity behavior. These results have significant implications for the management behavior of the government.

16.
Int J Gynecol Cancer ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39019492

ABSTRACT

OBJECTIVES: The aim of our study was to evaluate the feasibility of the modified International Germ Cell Cancer Collaborative Group risk classification system in Chinese female patients with malignant ovarian germ cell tumors and to identify predictive factors to enhance the risk classification system. METHODS: In this retrospective cohort analysis, patients with malignant ovarian germ cell tumors who received surgery with/without chemotherapy were included. These patients had been followed-up by Peking Union Medical College Hospital between 2011 to 2020. Patients without complete medical records or no follow-up information were excluded. RESULTS: The study enrolled a total of 271 patients. The risk model classified 106 (39.1%) patients as good-, 84 (31%) as intermediate-, and 81 (29.9%) as poor-risk. With a median follow-up time of 34 months (range 2-147), 48 (17.7%) recurrence and 16 (5.9%) deaths were observed. The risk classification significantly correlated with 3 year disease-free survival and overall survival (log rank p<0.001 and p=0.003, respectively). The survival outcomes of disease-free survival and overall survival were not statistically different among risk groups in patients who received neoadjuvant chemotherapy (log rank p=0.77 and 0.41, respectively). Univariate and multivariable analysis showed that tumor stage (p=0.033, hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.06 to 3.96) was significantly associated with relapse or progression of disease. Patients over age 40 years exhibited a poor prognosis. CONCLUSION: The modified International Germ Cell Cancer Collaborative Group risk classification system was efficacious in patients with malignant ovarian germ cell tumors and was significantly associated with disease-free survival and overall survival. Risk assessment after neoadjuvant chemotherapy may be more predictive than stratification at initial diagnosis. Age and tumor stage were definitive prognostic factors for germ cell tumors, which may need to be incorporated in the stratification system.

17.
Int J Gynecol Cancer ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39074931

ABSTRACT

OBJECTIVE: Non-platinum chemotherapy is used in platinum resistant/refractory ovarian cancer patients but offers limited efficacy, especially in those who develop platinum resistance after ≤2 lines of platinum based chemotherapy. This phase II study aimed to evaluate the efficacy and safety of oral niraparib plus etoposide in platinum resistant/refractory ovarian cancer. METHODS: Platinum resistant/refractory ovarian cancer patients after ≤2 lines of platinum based chemotherapy, histologically confirmed as non-mucinous epithelial ovarian cancer, regardless of biomarker status, were eligible. Patients received niraparib with a starting dose of 200 mg/100 mg alternate once a day, and oral etoposide of 50 mg once a day, on days 1-20 of 30 days per cycle for a maximum of 6-8 cycles, followed by niraparib until disease progression or intolerable toxicity. The primary endpoint was investigator assessed progression free survival. RESULTS: 29 patients were enrolled from 22 May 2020 to 3 February 2023; 26 patients were included in the efficacy analysis set as per protocol. Median progression free survival was 4.2 months (95% confidence interval (CI) 3.9 to 4.4). Overall response rate was 26.9% (95% CI 8.7 to 45.2). Disease control rate was 57.7% (95% CI 37.3 to 78.0). Overall response rate in patients with a BRCA mutation and homologous recombination deficiency was 50% and 41.7%, respectively. Median progression free survival in patients with primary platinum resistance was 4.5 months (95% CI 3.6 to 5.3). 29 patients were included in the safety analysis set, and 8 (28%) patients experienced treatment related adverse events of grade ≥3. There was no treatment related discontinuation. CONCLUSIONS: Niraparib combined with etoposide showed evidence of antitumor activity in platinum resistant/refractory ovarian cancer after ≤2 lines of platinum based chemotherapy, particularly in patients with a BRCA mutation, homologous recombination deficiency, or primary platinum resistance. This once-a-day oral combination was a convenient option. TRIAL REGISTRATION NUMBER: NCT04217798.

18.
Environ Sci Pollut Res Int ; 31(31): 44348-44360, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38951394

ABSTRACT

Aluminum electrolyte is a necessity for aluminum reduction cells; however, its stock is rising every year due to several factors, resulting in the accumulation of solid waste. Currently, it has become a favorable material for the resources of lithium, potassium, and fluoride. In this study, the calcification roasting-two-stage leaching process was introduced to extract lithium and potassium separately from aluminum electrolyte wastes, and the fluoride in the form of CaF2 was recycled. The separation behaviors of lithium and potassium under different conditions were investigated systematically. XRD and SEM-EDS were used to elucidate the phase evolution of the whole process. During calcification roasting-water leaching, the extraction efficiency of potassium was 98.7% under the most suitable roasting parameters, at which the lithium extraction efficiency was 6.6%. The mechanism analysis indicates that CaO combines with fluoride to form CaF2, while Li-containing and K-containing fluorides were transformed into water-insoluble LiAlO2 phase and water-soluble KAlO2 phase, respectively, thereby achieving the separation of two elements by water leaching. In the second acid-leaching stage, the extraction efficiency of lithium was 98.8% from water-leached residue under the most suitable leaching conditions, and CaF2 was obtained with a purity of 98.1%. The present process can provide an environmentally friendly and promising method to recycle aluminum electrolyte wastes and achieve resource utilization.


Subject(s)
Aluminum , Fluorides , Lithium , Potassium , Fluorides/chemistry , Lithium/chemistry , Aluminum/chemistry , Potassium/chemistry , Electrolytes/chemistry , Recycling
19.
Article in English | MEDLINE | ID: mdl-39074547

ABSTRACT

STUDY OBJECTIVE: The main objective is to evaluate the feasibility of laparoscopic fertility-sparing surgery in women with growing teratoma syndrome. DESIGN: Retrospective cohort study. SETTING: Chinese tertiary university hospital. PATIENTS: Patients with growing teratoma syndrome who underwent fertility-sparing surgery between January 2015 and August 2023. INTERVENTIONS: Baseline characteristics and surgical outcomes were evaluated, including clinical information, surgical procedures, operative time, intraoperative blood loss, complications, length of hospital stay, and follow-up information. MEASUREMENT AND MAIN RESULTS: Twenty-six patients with ovarian growing teratoma syndrome underwent fertility-sparing surgery: 12 had laparoscopic surgery and 14 underwent laparotomic surgery. In the laparoscopic group, the median age of the patients during initial management of immature teratoma or mixed malignant ovarian germ cell tumor was 14.0 years (interquartile range, 13.0-24.5 years). Eleven patients were nulliparous. The primary ovarian tumor was pure immature teratoma in 10 patients and mixed ovarian germ cell tumor in 2 patients. Complete laparoscopic tumor resection was achieved in 11 patients. Patients in the laparoscopic group had shorter median operative time (76.5 vs 180.0 minutes, p = .001), lower estimated blood loss (20.0 vs 400.0 mL, p <.001), and decreased postoperative hospital stay (2.0 vs 7.0 days, p <.001) compared with laparotomic surgery. There was no conversion to laparotomy and no perioperative complications. Histologic examination confirmed mature teratoma in all cases. During a median follow-up of 21.9 months (interquartile range, 7.6-44.9 months), 11 patients were alive without disease and 1 was alive with disease. One pregnancy was achieved postoperatively. CONCLUSION: Laparoscopic fertility-sparing surgery may represent a feasible option in well-selected patients with ovarian growing teratoma syndrome. Surgery should be performed in gynecologic oncology centers by experienced staff trained in endoscopic procedures. More research and long-time follow-up are needed to determine the oncologic outcomes and safety of laparoscopic surgery in this population.

20.
J Med Virol ; 96(7): e29805, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39011773

ABSTRACT

Heterogeneous nuclear protein U (HNRNPU) plays a pivotal role in innate immunity by facilitating chromatin opening to activate immune genes during host defense against viral infection. However, the mechanism by which HNRNPU is involved in Hepatitis B virus (HBV) transcription regulation through mediating antiviral immunity remains unknown. Our study revealed a significant decrease in HNRNPU levels during HBV transcription, which depends on HBx-DDB1-mediated degradation. Overexpression of HNRNPU suppressed HBV transcription, while its knockdown effectively promoted viral transcription, indicating HNRNPU as a novel host restriction factor for HBV transcription. Mechanistically, HNRNPU inhibits HBV transcription by activating innate immunity through primarily the positive regulation of the interferon-stimulating factor 2'-5'-oligoadenylate synthetase 3, which mediates an ribonuclease L-dependent mechanism to enhance innate immune responses. This study offers new insights into the host immune regulation of HBV transcription and proposes potential targets for therapeutic intervention against HBV infection.


Subject(s)
2',5'-Oligoadenylate Synthetase , Hepatitis B virus , Immunity, Innate , Transcription, Genetic , Humans , Hepatitis B virus/immunology , Hepatitis B virus/genetics , 2',5'-Oligoadenylate Synthetase/genetics , 2',5'-Oligoadenylate Synthetase/metabolism , Host-Pathogen Interactions/immunology , Host-Pathogen Interactions/genetics , Hep G2 Cells , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B/genetics , Viral Regulatory and Accessory Proteins/genetics , Viral Regulatory and Accessory Proteins/metabolism , Viral Regulatory and Accessory Proteins/immunology , Trans-Activators
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