Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with <20 sites (HR 0.69, 95% CI 0.46-1.03). Patients with a complete resection had the most favorable outcome, with a median OS of 73.0 months. Twenty-four of 182 (13.2%) patients remained relapse free and alive >60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .
Fusarium crown rot (FCR) is an important and devastating disease of wheat (Triticum aestivum) caused by the fungus Fusarium pseudograminearum and related pathogens. Using two distinct susceptible cultivars, we investigated the isolation frequencies of F. pseudograminearum and quantified its biomass accumulation and the levels of the associated toxins deoxynivalenol (DON) and DON-3-glucoside (D3G) in inoculated field-grown wheat plants. We detected F. pseudograminearum in stem, peduncle, rachis, and husk tissues, but not in grains, whereas DON and D3G accumulated in stem, rachis, husk, and grain tissues. Disease severity was positively correlated with the frequency of pathogen isolation, F. pseudograminearum biomass, and mycotoxin levels. The amount of F. pseudograminearum biomass and mycotoxin contents in asymptomatic tissue of diseased plants were associated with the distance of the tissue from the diseased internode and the disease severity of the plant. Thus, apparently healthy tissue may harbor F. pseudograminearum and contain associated mycotoxins. This research helps clarify the relationship between F. pseudograminearum occurrence, F. pseudograminearum biomass, and mycotoxin accumulation in tissues of susceptible wheat cultivars with or without disease symptoms, providing information that can lead to more effective control measures.
Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].
[This corrects the article DOI: 10.1016/j.gendis.2022.05.030.].
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumors, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years. The primary endpoint was progression-free survival assessed by blinded independent central review. At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32-0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively. Senaparib significantly improved progression-free survival versus placebo in patients with advanced ovarian cancer after response to first-line platinum-based chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated. These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .
BACKGROUND: Calcium and magnesium are important micronutrients necessary for normal body functioning. OBJECTIVE: The objective of the study was to approximate usual nutrient intakes and estimate proportion of adults meeting the estimated average requirement (EAR) of calcium and magnesium from diet, and diet plus supplements (total intake). Trends in the proportion of adults meeting the EAR were estimated by sex, age, and race and ethnicity. DESIGN: The study utilized data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of the United States civilian and noninstitutionalized population. PARTICIPANTS AND SETTING: The continuous NHANES survey data from 2003-2004 through 2017-2018 for dietary intake, and 2007-2008 through 2017-2018 for total intake were analyzed. The study sample included males and females (not lactating/pregnant) aged ≥19 years with two reliable 24-hour dietary recalls and energy intake >500 - <6000 kcal/day (n=35,037). MAIN OUTCOME MEASURES: Mean daily intake and trends of proportion of adults meeting/exceeding the EAR for calcium and magnesium were estimated. STATISTICAL ANALYSES PERFORMED: The National Cancer Institute's (NCI) method was used to calculate daily intakes for calcium and magnesium by demographic subgroups. SAS SURVEYMEAN AND SURVEYFREQ procedures were used to estimate means and standard errors (SE) for continuous variables and frequencies and percentages for categorical variables, and two sample t-test for p-values. Trends were estimated with NCI's Joinpoint trend analysis program. RESULTS: Mean daily dietary calcium intake and proportions of adults meeting the EAR from both diet and supplements was lowest among females (859 mg / 61.9%), adults aged ≥71 years (865 mg / 60.3%) and non-Hispanic black (NHB) individuals (782 mg / 48.6%) compared to males, younger age groups and other races and ethnicities. Magnesium intake reported from diet was lowest in adults ≥71 years (276 mg) while total magnesium intake and proportion of meeting the EAR from both diet and supplements was lowest in females (302 mg) and males (52%) respectively, adults 19-30 years (305 mg / 48.5%) and NHB individuals (274 mg / 35.5%). The trends in the proportion of females and NH white (NHW) adults meeting the EAR from total calcium intake decreased significantly (p-value <0.05) by 2.9% and 2.0% respectively. CONCLUSIONS: Females and adults aged ≥71 years had the lowest reported mean daily dietary calcium intake and proportion meeting the EAR for calcium from diet and supplements. Males and adults aged 19-30 years had the lowest proportion meeting the EAR for magnesium from diet and supplements with adults aged 19-30 years also having the lowest reported total magnesium intake from diet and supplements. NHB individuals had the lowest proportion of meeting the EARs for calcium and magnesium from reported total intake. The trends in the proportion of females and NHW individuals meeting the EARs for calcium through total intake decreased over time and remained stable in other subpopulations and for magnesium.
Introduction: Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification. Methods: The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS. Results: The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis. Conclusion: In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.
BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.
B7-H1 Antigen , Biomarkers, Tumor , Maintenance Chemotherapy , Ovarian Neoplasms , Phthalazines , Piperazines , Humans , Female , Phthalazines/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Piperazines/therapeutic use , Biomarkers, Tumor/genetics , Middle Aged , Maintenance Chemotherapy/methods , Aged , Adult , Prospective Studies , Neoplasm Recurrence, Local/drug therapy , BRCA2 Protein/genetics , Antineoplastic Agents/therapeutic use , BRCA1 Protein/genetics , Homologous Recombination
Introduction: Few studies have examined the associations of intimate partner violence (IPV) exposure during pregnancy and types of IPV with antenatal depression among underserved pregnant women. Methods: Data came from participants from a Healthy Start program in South Carolina between 2015 and 2019 (n = 1,629). The first two questions in the Woman Abuse Screening Tool (WAST) were used to measure IPV exposure, that is, having a problematic relationship with their partner. Those who had IPV exposure were assessed with six additional questions of the WAST. Principal component analysis was conducted on the 8-item WAST data to identify underlying types of IPV exposure. Antenatal depression was defined as the Center for Epidemiologic Studies Depression scores ≥16. Results: Participants were racially diverse (71% black, 21% white) with 85% Medicaid recipients. Nearly 12% of participants reported IPV exposure and 30% reported antenatal depression. The odds of having IPV exposure were higher among unmarried women, those with less than a high school education, and those who lacked family support. The odds of having antenatal depression were 2.5 times higher (95% CI: 1.9-3.5) among women with IPV exposure. After controlling for covariates, a one-point increase in the scores for psychological IPV (Factor 1) or a problematic relationship (Factor 3) was associated with increased odds of antenatal depression. Conclusion: This is one of the first studies to estimate the prevalence of IPV exposure using a proxy measure (a problematic relationship) among underserved U.S. pregnant women. Its positive association with antenatal depression suggests the utility of screening for a problematic relationship using a two-item WAST and providing assistance to those with IPV exposure.
OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.
BACKGROUND: The COVID-19 pandemic has significantly affected maternal care services especially for minoritized individuals, creating challenges for both service users (i.e., African American and Hispanic pregnant/postpartum women) and maternal care providers (MCPs). Guided by a socioecological framework, this study aims to investigate the experiences of African American and Hispanic pregnant and postpartum women, as well as MCPs, in accessing and providing maternal care services during the COVID-19 pandemic in the Deep South. METHODS: We conducted semi-structured interviews with 19 African American women, 20 Hispanic women, and 9 MCPs between January and August 2022. Participants were recruited from Obstetrics and Gynecology clinics, pediatric clinics, and community health organizations in South Carolina, and all births took place in 2021. Interview transcripts were analyzed thematically. RESULTS: Maternal care utilization and provision were influenced by various factors at different socioecological levels. At the intrapersonal level, women's personal beliefs, fears, concerns, and stress related to COVID-19 had negative impacts on their experiences. Some women resorted to substance use as a coping strategy or home remedy for pregnancy-induced symptoms. At the interpersonal level, family and social networks played a crucial role in accessing care, and the discontinuation of group-based prenatal care had negative consequences. Participants reported a desire for support groups to alleviate the pressures of pregnancy and provide a platform for shared experiences. Language barriers were identified as an obstacle for Hispanic participants. Community-level impacts, such as availability and access to doulas and community health workers, provided essential information and support, but limitations in accessing doula support and implicit bias were also identified. At the institutional level, mandatory pre-admission COVID-19 testing, visitation restrictions, and reduced patient-MCP interactions were women's common concerns. Short staffing and inadequate care due to the impact of COVID-19 on the health care workforce were reported, along with anxiety among MCPs about personal protective equipment availability. MCPs emphasized the quality of care was maintained, with changes primarily attributed to safety protocols rather than a decline in care quality. CONCLUSION: The pandemic has disrupted maternal care services. To overcome these issues, health facilities should integrate community resources, adopt telehealth, and develop culturally tailored education programs for pregnant and postpartum women. Supporting MCPs with resources will enhance the quality of care and address health disparities in African American and Hispanic women.
COVID-19 , Hispanic or Latino , Maternal Health Services , Humans , COVID-19/epidemiology , COVID-19/psychology , Female , Pregnancy , Adult , Hispanic or Latino/psychology , South Carolina/epidemiology , Postpartum Period/psychology , Black or African American/psychology , SARS-CoV-2 , Pregnant Women/psychology , Pandemics , Health Personnel/psychology , Young Adult , Patient Acceptance of Health Care , Health Services Accessibility
Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.
Ovarian Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Laparoscopy/methods , Neoplasm Recurrence, Local , Maintenance Chemotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/genetics , Antineoplastic Agents/therapeutic use , Asia, Eastern , East Asian People
OBJECTIVE: We examined the association between antenatal depressive symptoms and adverse birth outcomes in Midland Healthy Start (MHS) participants and determined whether receiving mental health services reduced the odds of adverse outcomes among those with elevated antenatal depressive symptoms. METHOD: Data from a retrospective cohort of participants (N = 1,733) served by the MHS in South Carolina (2010-2019) were linked with their birth certificates. A score of ≥16 on the Center for Epidemiologic Studies Depression Scale was defined as elevated antenatal depressive symptoms. Services provided by MHS were categorized into: (1) receiving mental health services, (2) receiving other services, and (3) not receiving any services. Adverse birth outcomes included preterm birth, low birth weight, and small for gestational age. RESULTS: Around 31 % had elevated antenatal depressive symptoms. The prevalences of preterm birth, low birthweight, and small for gestational age were 9.5 %, 9.1 %, and 14.6 %, respectively. No significant associations were observed between elevated depressive symptoms and adverse outcomes. Among women with elevated antenatal depressive symptoms, the odds for small for gestational age were lower in those who received mental health services (AOR 0.33, 95 % CI 0.15-0.72) or other services (AOR 0.34, 95 % CI 0.16-0.74) compared to those who did not receive any services. The odds for low birth weight (AOR 0.34, 95 % CI 0.13-0.93) were also lower in those who received mental health services. CONCLUSIONS: Receiving screening and referral services for antenatal depression reduced the risks of having small for gestational age or low birth weight babies among MHS participants.
Depression , Mental Health Services , Pregnancy Outcome , Humans , Female , Pregnancy , Adult , Retrospective Studies , Depression/epidemiology , Depression/psychology , Mental Health Services/statistics & numerical data , South Carolina/epidemiology , Pregnancy Outcome/epidemiology , Cohort Studies , Infant, Newborn , Pregnancy Complications/epidemiology , Pregnancy Complications/psychology , Infant, Low Birth Weight , Premature Birth/epidemiology
BACKGROUND: Sleep problems are associated with abnormal cardiovascular biomarkers and an increased risk of cardiovascular diseases (CVDs). However, studies investigating associations between sleep problems and CVD biomarkers have reported conflicting findings. This study examined the associations between sleep problems and CVD biomarkers in the United States. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) and analyses were restricted to adults ≥ 20 years (n = 23,749). CVD biomarkers [C-reactive Protein (CRP), low-density lipoproteins, high-density lipoproteins (HDL), triglycerides, insulin, glycosylated hemoglobin (HbA1c), and fasting blood glucose] were categorized as abnormal or normal using standardized cut-off points. Sleep problems were assessed by sleep duration (short [≤ 6 h], long [≥ 9 h], and recommended [> 6 to < 9 h) and self-reported sleep disturbance (yes, no). Multivariable logistic regression models explored the associations between sleep duration, sleep disturbance, and CVD biomarkers adjusting for sociodemographic characteristics and lifestyle behaviors. RESULTS: The mean sleep duration was 7.1 ± 1.5 h and 25.1% of participants reported sleep disturbances. Compared to participants with the recommended sleep duration, those with short sleep duration had higher odds of abnormal levels of HDL (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.05-1.39), CRP (aOR = 3.08, 95% CI = 1.18-8.05), HbA1c (aOR = 1.25, 95% CI = 1.05-1.49), and insulin (aOR = 1.24, 95% CI = 1.03-1.51). Long sleep duration was associated with increased odds of abnormal CRP (aOR = 6.12, 95% CI = 2.19-17.15), HbA1c (aOR = 1.54, 95% CI = 1.09-2.17), and blood glucose levels (aOR = 1.45, 95% CI = 1.07-1.95). Sleep disturbance predicted abnormal triglyceride (aOR = 1.18, 95% CI = 1.01-1.37) and blood glucose levels (aOR = 1.24, 95% CI = 1.04-1.49). CONCLUSION: Short and long sleep durations were positively associated with abnormal CRP, HDL, HbA1c, blood glucose, and insulin levels, while sleep disturbance was associated with abnormal triglyceride and blood glucose levels. Since sleep is a modifiable factor, adopting healthy sleeping habits may create a balanced metabolism and reduce the risk of developing a CVD. Our study may provide insights into the relationship between sleep duration, sleep disturbance, and CVD risk.
Cardiovascular Diseases , Sleep Wake Disorders , Adult , Humans , United States/epidemiology , Cardiovascular Diseases/epidemiology , Nutrition Surveys , Sleep Duration , Glycated Hemoglobin , Blood Glucose/metabolism , Biomarkers , C-Reactive Protein/analysis , Sleep , Sleep Wake Disorders/epidemiology , Insulin , Lipoproteins, HDL , Triglycerides , Risk Factors
ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer (PCa) is the most common malignancy of the male genitourinary system and currently lacks effective treatment. Semen Impatientis, the dried ripe seed of Impatiens balsamina L., is described by the Chinese Pharmacopoeia as a traditional Chinese medicine (TCM) and is used in clinical practice to treat tumors, abdominal masses, etc. In our previous study, the ethyl acetate extracts of Semen Impatientis (EAESI) was demonstrated to be the most effective extract against PCa among various extracts. However, the biological effects of EAESI against PCa in vivo and the specific antitumor mechanisms involved remain unknown. AIM OF THE STUDY: In this study, we aimed to investigate the antitumor effect of EAESI on PCa in vitro and in vivo by performing network pharmacology analysis, transcriptomic analysis, and experiments to explore and verify the underlying mechanisms involved. MATERIALS AND METHODS: The antitumor effect of EAESI on PCa in vitro and in vivo was investigated via CCK-8, EdU, flow cytometry, and wound healing assays and xenograft tumor models. Network pharmacology analysis and transcriptomic analysis were employed to explore the underlying mechanism of EAESI against PCa. Activating transcription factor 3 (ATF3) and androgen receptor (AR) were confirmed to be the targets of EAESI against PCa by RTâqPCR, western blotting, and rescue assays. In addition, the interaction between ATF3 and AR was assessed by coimmunoprecipitation, immunofluorescence, and nuclear-cytoplasmic separation assays. RESULTS: EAESI decreased cell viability, inhibited cell proliferation and migration, and induced apoptosis in AR+ and AR- PCa cells. Moreover, EAESI suppressed the growth of xenograft tumors in vivo. Network pharmacology analysis revealed that the hub targets of EAESI against PCa included AR, AKT1, TP53, and CCND1. Transcriptomic analysis indicated that activating transcription factor 3 (ATF3) was the most likely critical target of EAESI. EAESI downregulated AR expression and decreased the transcriptional activity of AR through ATF3 in AR+ PCa cells; and EAESI promoted the expression of ATF3 and exerted its antitumor effect via ATF3 in AR+ and AR- PCa cells. CONCLUSIONS: EAESI exerts good antitumor effects on PCa both in vitro and in vivo, and ATF3 and AR are the critical targets through which EAESI exerts antitumor effects on AR+ and AR- PCa cells.
Acetates , Activating Transcription Factor 3 , Mice, Nude , Network Pharmacology , Prostatic Neoplasms , Receptors, Androgen , Xenograft Model Antitumor Assays , Male , Animals , Humans , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Activating Transcription Factor 3/metabolism , Activating Transcription Factor 3/genetics , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Acetates/chemistry , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Mice , Apoptosis/drug effects , Cell Proliferation/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Transcriptome/drug effects , Mice, Inbred BALB C , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic/drug effects
Background: Sleep disorders are one of the most common non-motor symptoms in PD. It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. Currently, there are numerous non-pharmacological interventions available to improve sleep quality in PD, with disagreement as to which intervention is most effective. This network meta-analysis was performed to compare and rank non-pharmacological interventions to explore their efficacy in improving sleep quality in PD and to select the best interventions, with a view to providing references and bases for the development of clinical treatments and care programs. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched from inception to December 6, 2023. Two authors independently screened all studies, extracted the data, and evaluated risk of bias of included studies. STATA software version 17.0 was used to conduct the network meta-analysis. Results: Our network meta-analysis included 29 studies involving 1,477 participants and 16 non-pharmacological interventions. Although most nonpharmacological interventions showed non-significant effects, the surface under the cumulative ranking curve (SUCRA) values indicated that the best non-pharmacological intervention for sleep disorders was massage therapy (97.3%), followed by music therapy (94.2%), and Treadmill training (85.7%). Conclusion: Massage therapy can be considered as an effective therapy for improving sleep quality in patients with PD. Due to limited quantity and quality of the included studies, more high quality studies are required to verify the conclusions of this network meta-analysis. Systematic review registration: identifier CRD42023429339, PROSPERO (york.ac.uk).
Crop yield potential is constrained by the inherent trade-offs among traits such as between grain size and number. Brassinosteroids (BRs) promote grain size, yet their role in regulating grain number is unclear. By deciphering the clustered-spikelet rice germplasm, we show that activation of the BR catabolic gene BRASSINOSTEROID-DEFICIENT DWARF3 (BRD3) markedly increases grain number. We establish a molecular pathway in which the BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 phosphorylates and stabilizes OsMADS1 transcriptional factor, which targets TERMINAL FLOWER1-like gene RICE CENTRORADIALIS2. The tissue-specific activation of BRD3 in the secondary branch meristems enhances panicle branching, minimizing negative effects on grain size, and improves grain yield. Our study showcases the power of tissue-specific hormonal manipulation in dismantling the trade-offs among various traits and thus unleashing crop yield potential in rice.
Brassinosteroids , Edible Grain , Oryza , Plant Proteins , Brassinosteroids/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Edible Grain/genetics , Edible Grain/growth & development , Edible Grain/metabolism , Gene Expression Regulation, Plant , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3/metabolism , Oryza/genetics , Oryza/growth & development , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism
INTRODUCTION: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. MATERIALS AND METHODS: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. RESULTS: Among 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35-5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49-3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58-2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55-3.13, P = 0.515) for non-endometrioid EC patients. CONCLUSION: LVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Prognosis , Retrospective Studies , Carcinoma, Endometrioid/surgery , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Proportional Hazards Models , Neoplasm Staging
The inhalation of zinc chloride (ZnCl2) smoke is one of common resources of lung injury, potentially resulting in severe pulmonary complications and even mortality. The influence of ZnCl2 smoke on lysine succinylation (Ksucc) in the lungs remains uncertain. In this study, we used a ZnCl2 smoke inhalation mouse model to perform global proteomic and lysine succinylome analyses. A total of 6781 Ksucc sites were identified in the lungs, with injured lungs demonstrating a reduction to approximately 2000 Ksucc sites, and 91 proteins exhibiting at least five differences in the number of Ksucc sites. Quantitative analysis revealed variations in expression of 384 proteins and 749 Ksucc sites. The analysis of protein-protein interactions was conducted for proteins displaying differential expression and differentially expressed lysine succinylation. Notably, proteins with altered Ksucc exhibited increased connectivity compared with that in differentially expressed proteins. Beyond metabolic pathways, these highly connected proteins were also involved in lung injury-associated pathological reactions, including processes such as focal adhesion, adherens junction, and complement and coagulation cascades. Collectively, our findings contribute to the understanding of the molecular mechanisms underlaying ZnCl2 smoke-induced lung injury with a specific emphasis on lysine succinylation. These findings could pave the way for targeted interventions and therapeutic strategies to mitigate severe pulmonary complications and mortality associated with such injuries in humans.
