Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

PIBF1 regulates multiple gene expression via impeding long-range chromatin interaction to drive the malignant transformation of HPV16 integration epithelial cells.

INTRODUCTION: Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. OBJECTIVES: We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. METHODS: We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. RESULTS: We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. CONCLUSION: We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

One-step rolling fabrication of VO2 tubular bolometers with polarization-sensitive and omnidirectional detection.

Uncooled infrared detection based on vanadium dioxide (VO2) radiometer is highly demanded in temperature monitoring and security protection. The key to its breakthrough is to fabricate bolometer arrays with great absorbance and excellent thermal insulation using a straightforward procedure. Here, we show a tubular bolometer by one-step rolling VO2 nanomembranes with enhanced infrared detection. The tubular geometry enhances the thermal insulation, light absorption, and temperature sensitivity of freestanding VO2 nanomembranes. This tubular VO2 bolometer exhibits a detectivity of ~2 × 108 cm Hz1/2 W-1 in the ultrabroad infrared spectrum, a response time of ~2.0 ms, and a calculated noise-equivalent temperature difference of 64.5 mK. Furthermore, our device presents a workable structural paradigm for polarization-sensitive and omnidirectional light coupling bolometers. The demonstrated overall characteristics suggest that tubular bolometers have the potential to narrow performance and cost gap between photon detectors and thermal detectors with low cost and broad applications.

Applying Life History Theory to Understand Earlier Onset of Puberty: An Adolescent Brain Cognitive Development Cohort Analysis.

PURPOSE: Life history theory posits that multigenerational exposure to adversity and deprivation influences childhood growth and development, including pubertal maturation. We applied this ecological, evolutionary theory to examine the contributions of distal and proximal adversity on early puberty, a potentially important marker for population health. METHODS: Baseline data from 5,645 girls in the adolescent brain cognitive development study were included. Early puberty was defined as midlate/post pubertal development by age 9-11 years. The contributions of multigenerational Black/Indigenous (Black, Indigenous and People of Color [BIPOC]) or Hispanic identities, intergenerational mental health, economic deprivation, personal trauma exposure and mental health, and proximal biological factors of premature birth and body mass index on early puberty were examined with hierarchical modeling. RESULTS: 1,225 girls (21.7%) had early puberty. BIPOC/Hispanic identity, familial adversity, economic deprivation, personal trauma, depression, and a higher body mass index contributed significantly toward early puberty. The effect of multigenerational adversity remained significant across models, but the likelihood of early puberty decreased sequentially for BIPOC and Hispanic youth as proximal adversities were added (e.g., OR decreased from 2.93 to 2.38 for BIPOC youth), supporting a synergistic effect of layered adversity on early puberty. DISCUSSION: This analysis supports life history theory as a coherent framework to understand early puberty among girls. Findings suggest monitoring pubertal timing as a population health indictor, like birth weight, prematurity, or life expectancy. Addressing early puberty may require policy and social changes to mitigate the negative impact of multiple layers of adversity including racial/ethnic disadvantage, family, and individual mental health and trauma, as well as economic insecurity.

Development of On-DNA Cyclic Imide Synthesis for DNA Encoded Library Construction.

Here, we describe a novel method for the on-DNA synthesis of cyclic imides, an important class of molecules that includes several well-known medications. Significantly, the new method enabled on-DNA synthesis under mild conditions with high conversions and a broad functional group tolerance, utilizing ubiquitous bifunctional amines and bis-carboxylic acid, or alkyl halides, and therefore served as the linchpin for DNA encoded library (DEL) synthesis. The mechanism study of off-DNA and on-DNA chemical transformations revealed unique insights in contrast to conventional chemical transformation.

Associations of Co-occurring Symptom Trajectories With Sex, Race, Ethnicity, and Health Care Utilization in Children.

Importance: Co-occurring physical and psychological symptoms during childhood and early adolescence may increase risk of symptom persistence into adulthood. Objective: To describe co-occurring pain, psychological, and sleep disturbance symptom (pain-PSS) trajectories in a diverse cohort of children and the association of symptom trajectory with health care utilization. Design, Setting, and Participants: This cohort study was a secondary analysis of longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, collected between 2016 and 2022 at 21 research sites across the US. Participants included children with 2 to 4 complete annual symptom assessments. Data were analyzed from November 2022 to March 2023. Main Outcomes and Measures: Four-year symptom trajectories were derived from multivariate latent growth curve analyses. Pain-PSS scores, including depression and anxiety, were measured using subscales from the Child Behavior Checklist and the Sleep Disturbance Scale of Childhood. Nonroutine medical care and mental health care utilization were measured using medical history and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) items. Results: A total of 11 473 children (6018 [52.5%] male; mean [SD] age at baseline, 9.91 [0.63] years) were included in analyses. Four no pain-PSS and 5 pain-PSS trajectories were supported with good or excellent model fit (predicted probabilities, 0.87-0.96). Most children (9327 [81.3%]) had asymptomatic or low, intermittent, or single symptom trajectories. Approximately 1 in 5 children (2146 [18.7%]) had moderate to high co-occurring symptom trajectories that persisted or worsened. Compared with White children, there was a lower relative risk of having moderate to high co-occurring symptom trajectories among Black children (adjusted relative risk ratio [aRRR] range, 0.15-0.38), Hispanic children (aRRR range, 0.58-0.67), and children who identified as another race (including American Indian, Asian, Native Hawaiian, and other Pacific Islader; aRRR range, 0.43-0.59). Less than half of children with moderate to high co-occurring symptom trajectories used nonroutine health care, despite higher utilization compared with asymptomatic children (nonroutine medical care: adjusted odds ratio [aOR], 2.43 [95% CI, 1.97-2.99]; mental health services: aOR, 26.84 [95% CI, 17.89-40.29]). Black children were less likely to report nonroutine medical care (aOR, 0.61 [95% CI, 0.52-0.71]) or mental health care (aOR, 0.68 [95% CI, 0.54-0.87]) than White children, while Hispanic children were less likely to have used mental health care (aOR, 0.59 [95% CI, 0.47-0.73]) than non-Hispanic children. Lower household income was associated with lower odds of nonroutine medical care (aOR, 0.87 [95% CI, 0.77-0.99]) but not mental health care. Conclusions and Relevance: These findings suggest there is a need for innovative and equitable intervention approaches to decrease the potential for symptom persistence during adolescence.

Associations Between Vascular Risk Factor Levels and Cognitive Decline Among Stroke Survivors.

Importance: Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain. Objective: To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline. Design, Setting, and Participants: Individual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023. Exposures: Time-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: A total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (-0.04 points/y faster per each 10-mg/dL increase [95% CI, -0.08 to -0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (-0.05 points/y faster per 10-mg/dL increase [95% CI, -0.09 to -0.01 points/y]; P = .01; -0.07 points/y faster per 10-mg/dL increase [95% CI, -0.11 to -0.03 points/y]; P = .002) but not executive function or memory declines. Conclusions and Relevance: In this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

EREG is a risk factor for the prognosis of patients with cervical cancer.

Background: Cervical cancer continues to threaten women's health worldwide. Identifying critical oncogenic molecules is important to drug development and prognosis prediction for patients with cervical cancer. Recent studies have demonstrated that epiregulin (EREG) is upregulated in various cancer types, which contributes to cancer progression by triggering the EGFR signaling pathway. However, the role of EREG is still unclear. Methods: In this study, we first conducted a comprehensive biological analysis to investigate the expression of EREG in cervical cancer. Then, we investigated the correlations between EREG expression level and clinicopathological features. In addition, we validated the effects of EREG expression on the proliferation and apoptosis of cervical cancer cells. Results: Based on the public database, we found that the expression of EREG was higher in advanced cervical cancer samples. Survival analysis showed that EREG was a risk factor for the prognosis of cervical cancer. In vitro experiments demonstrated that EREG knockdown undermined proliferation and promoted apoptosis in cancer cells. Conclusion: EREG plays a vital role in the progression of cervical cancer, which contributes to hyperactive cell proliferation and decreased cell apoptosis. It might be a valuable target for prognosis prediction and drug development for cervical cancer in the future.

Targeting PARP for the optimal immunotherapy efficiency in gynecologic malignancies.

Gynecologic cancer, which includes ovarian, cervical, endometrial, vulvar, and vaginal cancer, is a major health concern for women all over the world. Despite the availability of various treatment options, many patients eventually progress to advanced stages and face high mortality rates. PARPi (poly (ADP-ribose) polymerase inhibitor) and immune checkpoint inhibitor (ICI) have both shown significant efficacy in the treatment of advanced and metastatic gynecologic cancer. However, both treatments have limitations, including inevitable resistance and a narrow therapeutic window, making PARPi and ICI combination therapy a promising approach to treating gynecologic malignancies. Preclinical and clinical trials have looked into the combination therapy of PARPi and ICI. PARPi improves ICI efficacy by inducing DNA damage and increasing tumor immunogenicity, resulting in a stronger immune response against cancer cells. ICI, conversly, can increase PARPi sensitivity by priming and activating immune cells, consequently prompting immune cytotoxic effect. Several clinical trials in gynecologic cancer patients have investigated the combination therapy of PARPi and ICI. When compared to monotherapy, the combination of PARPi and ICI increased progression-free survival and overall survival in ovarian cancer patients. The combination therapy has also been studied in other types of gynecologic cancer, including endometrial and cervical cancer, with promising results. Finally, the combination therapeutic strategy of PARPi and ICI is a promising approach in the treatment of gynecologic cancer, particularly advanced and metastatic stages. Preclinical studies and clinical trials have demonstrated the safety and efficacy of this combination therapy in improving patient outcomes and quality of life.

Reaching Populations to Address Disparities in Cancer Care Delivery: Results From a Six-Site Initiative.

BACKGROUND: Large segments of the US population do not receive quality cancer care due to pervasive and systemic inequities, which can increase morbidity and mortality. Multicomponent, multilevel interventions can address inequities and improve care, but only if they reach communities with suboptimal access. Intervention studies often underenroll individuals from historically excluded groups. METHODS: The Alliance to Advance Patient-Centered Cancer Care includes 6 grantees across the United States who implemented unique multicomponent, multilevel intervention programs with common goals of reducing disparities, increasing engagement, and improving the quality of care for targeted populations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework informed the evaluation efforts across sites. Each Alliance site identified their intended populations, which included underrepresented minorities (eg, Black and Latinx persons), individuals who prefer a language other than English, and rural residents. We evaluated the demographic characteristics of participants to determine program reach. RESULTS: Between 2018 and 2020, a total of 2,390 of 5,309 potentially eligible participants were enrolled across the 6 sites. The proportion of enrolled individuals with selected characteristics included 38% (n=908) Black adults, 24% (n=574) Latinx adults, 19% (n=454) preferring a language other than English, and 30% (n=717) rural residents. The proportion of those enrolled who were the intended population was commensurate to the proportion with desired characteristics in those identified as potentially eligible. CONCLUSIONS: The grantees met or exceeded enrollments from their intended populations who have been underserved by quality cancer care into patient-centered intervention programs. Intentional application of recruitment/engagement strategies is needed to reach individuals from historically underserved communities.

Dual color infrared photodetector with superconducting metamaterials.

Superconducting photodetection offers a wide spectral coverage ranging from the microwave to X-ray, and in the short wavelength range, single photon sensitivity can be achieved. However, in the longer wavelength infrared region, the system detection efficiency is low due to the lower internal quantum efficiency and weak optical absorption. Here, we utilized the superconducting metamatieral to enhance the light coupling efficiency and reach nearly perfect absorption at dual color infrared wavelengths. Dual color resonances arise from hybridization of local surface plasmon mode of the metamaterial structure and the Fabry-Perot-like cavity mode of metal (Nb)-dielectric (Si)-metamatieral (NbN) tri-layer structure. We demonstrated that, at the working temperature of 8 K slightly below TC ∼8.8 K, this infrared detector exhibits the peak responsivity of 1.2 × 106V/W and 3.2 × 106V/W at two resonant frequencies 36.6 THz and 104 THz, respectively. The peak responsivity is enhanced about ∼8 and ∼22 times, respectively, compared to that of non-resonant frequency (67 THz). Our work provides a way to harvest infrared light efficiently and hence improve the sensitivity of superconducting photodetectors in multispectral infrared range, which may find promising applications in thermal image and gas sensing etc.

Preparation of Heavy Metal Trapping Flocculant Polyacrylamide-Glutathione and Its Application for Cadmium Removal from Water.

In this study, a heavy metal trapping gel with multiple ligand groups was prepared for the first time using response surface methodology. The gel was produced by condensing and grafting glutathione as a grafting monomer onto the main polyacrylamide chain, based on the Mannich reaction mechanism with formaldehyde. FTIR, SEM, TG-DSC, and zeta potentials were used to characterize the gel. The results demonstrated that the gel was morphologically folded and porous, with a net-like structure, which enhanced its net trapping and sweeping abilities, and that glutathione was used to provide sulfhydryl groups to boost the metal trapping ability of polyacrylamide. Coagulation experiments showed that the highest efficiency of the removal of Cd ions from water samples was achieved when the concentration of polyacrylamide-glutathione was 84.48 mgL-1, the concentration of Cd was 10.0 mgL-1, the initial turbidity was 10.40 NTU, and the initial pH was 9.0. Furthermore, the presence of two cations, Cu and Zn, had an inhibitory effect on the removal of Cd ions. In addition, analysis of the zeta potential revealed the flocculation of polyacrylamide-glutathione. The flocculation mechanism of glutathione is mainly chelation, adsorption bridging, and netting sweeping.

Effects of lansoprazole and omeprazole Combined With Antimicrobial Agents on Gastric Juice pH and Inflammatory Factors in Elderly Patients With Hp Positive Gastric Ulcer.

Background: Helicobacter pylori (Hp) is one of the most prevalent pathogenic microorganisms in the world, which is related to gastric ulcer. Objective: To observe the effect of lansoprazole and omeprazole combined with antibiotics on gastric juice pH and inflammatory factors in elderly patients with Hp positive gastric ulcer. Design: This study was a prospective observation study. Setting: This study was performed in Department of Gastroenterology, First Affiliated Hospital of Soochow University. Participants: One hundred and ten elder patients with Hp positive gastric ulcer admitted to our hospital from January 2019 to May 2020. Intervention: The control group was treated with omeprazole combined with antibiotics, and the observation group was treated with lansoprazole combined with antibiotics. Primary outcome measures: The level of gastric juice pH, interleukin-1 (IL-1), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and heat shock protein-70 (HSP-70). Methods: The changes of gastric juice pH value, IL-1, IL-8, TNF-α and HSP-70 levels before and after treatment were detected in the two groups. The total effective rate, Hp eradication rate, mature type of regenerated mucosal tissue surrounding ulcer and adverse reaction rate were statistically analyzed. Results: The total effective rate and Hp eradication rate in the observation group were higher than those in the control group, while the adverse reaction rate in the observation group was lower than that in the control group (P < .05). After treatment, the pH value of gastric juice and HSP-70 in the observation group were higher than those in the control group, while the IL-1, IL-8 and TNF-α were lower than those in the control group (P < .05). The mature type of regenerated mucosal tissue structure around ulcer in the observation group was better than that in the control group (P < .05). Conclusion: The overall effect of lansoprazole combined with antibiotics in the treatment of Hp positive gastric ulcer in the elderly is better than that of omeprazole combined with antibiotics.

Case Report: Endoscopic manifestations and clinical features of small intestinal lymphangioma-A report of two cases.

Objective: The aims of this study were to analyze the clinical characteristics, auxiliary examinations, and treatment measures of small intestinal lymphangioma and to improve the clinical diagnostic ability of clinicians. Methods: This paper reports two cases of small intestinal lymphangioma in the Department of Gastroenterology, the First Affiliated Hospital of Soochow University, and makes a comprehensive analysis. Results: A 31-year-old woman went to the hospital with complaints of dizziness, fatigue, and anemia. A 52-year-old woman complained of upper abdominal pain and went to the hospital with abdominal pain awaiting investigation. Both patients were subjected to three major routine examinations, tumor complete set, CT, capsule endoscopy, and deep enteroscopy, and both of them underwent complete resection of the affected intestinal segment. Pathology showed that both patients had small intestinal lymphangioma. Conclusions: The clinical manifestations of small intestinal lymphangioma lack specificity. Capsule endoscopy and deep enteroscopy are helpful for clinical diagnosis, and pathological examination is still the gold standard. Surgical treatment can achieve better results.

Biopsychosocial Attributes of Single-region and Multi-region Body Pain During Early Adolescence: Analysis of the ABCD Cohort.

OBJECTIVES: Multi-region pain during adolescence is associated with a higher symptom burden and lower quality of life. The purpose of this study was to describe and compare the biopsychosocial attributes of single-region and multi-region pain among healthy young adolescents. MATERIALS AND METHODS: We analyzed data from 10,320 children aged 10.6 to 14 years who self-reported pain in the Adolescent Brain and Cognitive Development Study. Pain was coded as single-region or multi-region based on body map data. RESULTS: One in 5 young adolescents indicated recent multi-region pain. Sequential regression supported improved model fit when psychological and sociocultural factors were added to a biological model of pain; however, these models improved the classification of multi-region but not single-region pain. A significant interaction effect of sex and puberty remained constant across models with increased odds of pain at each advancing pubertal stage for both sexes compared with prepuberty, but no difference between girls and boys at late puberty (adjusted odds ratio [OR]=2.45 [1.72, 3.49] and adjusted OR=1.63 [1.20, 2.23], respectively). Psychological factors improved the classification of multi-region pain with significant effects of anxiety, somatic symptoms, and somnolence. Finally, compared with White and non-Hispanic children, Black and Hispanic children were less likely to report pain (adjusted OR=0.70 [0.61, 0.80]; adjusted OR=0.88 [0.78, 0.99], respectively) but had significantly higher pain interference when pain was present (adjusted OR=1.49 [1.29, 1.73] and adjusted OR=1.20 [1.06, 1.35], respectively). DISCUSSION: Pain is a biopsychosocial phenomenon, but psychological and sociocultural features may be more relevant for multi-region compared with single-region pain during early adolescence.

LncRNA HCP5 enhances the proliferation and migration of cervical cancer via miR-216a-5p/CDC42 axis.

To investigate the important roles of the cancer-promoting long non-coding RNAs (lncRNAs) in cervical cancer, the up-regulated lncRNAs and prognostic analysis were identified through Lnc2Cancer and Lncar. LncRNA-regulated miRNA and miRNA-target mRNA were analyzed based on starBase v2.0 and miTarbase to predict the lncRNA-miRNA-mRNA ceRNA network. Based on the above findings, the abnormally expressed histocompatibility leukocyte antigen complex P5 (HCP5) was identified in 31 cervical cancer patients through RT-qPCR. The stable cell lines were constructed to explore the effect of HCP5 on the promotion of cervical cancer and the regulatory role on the expression of miR-216a-5p and CDC42. Cell Counting Kit-8 (CCK8) assay, cell clone formation, and transwell assay were used to examine proliferation and migration ability of cervical cancer cells. The results displayed that the overexpression of HCP5 promoted cervical cancer cell proliferation and migration in vitro, and the elevated HCP5 can also promote tumor growth in vivo. Besides, RT-qPCR and western blot assay revealed that elevated HCP5 suppressed miR-216a-5p expression and then up-regulated the expression of CDC42. In contrast, knocking down HCP5 resulted in increased expression of miR-216a-5p and then downregulated the expression of CDC42. Rescue experiments also demonstrated that miR-216a-5p could in part intercept in promotion impact caused by HCP5 on cervical cancer cells. Above all, HCP5, as an oncogene, can promote proliferation and migration ability of cervical cancer via the regulation of the miR-216a-5p/CDC42 axis.

Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. METHODS: Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. RESULTS: From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. CONCLUSION: Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

Impacts of Neonatal Hospitalization on Families during the 2019 Coronavirus Pandemic.

OBJECTIVE: Limited data are available regarding family and financial well-being among parents whose infants were hospitalized during the 2019 coronavirus (COVID-19) pandemic. The study objective was to evaluate the family and financial well-being of parents whose infants were hospitalized in the neonatal intensive care unit (NICU) during COVID-19. STUDY DESIGN: Parents were recruited for this online, cross-sectional survey via support groups on social media. Data collection was completed between May 18, 2020 and July 31, 2020. The final sample consisted of 178 parents, who had an infant hospitalized in an NICU between February 1, 2020 and July 31, 2020. The primary outcomes were impact on family life and financial stability, as measured by the Impact on Family scale, an instrument that evaluates changes to family life as a result of infant or childhood illness. RESULTS: Of the 178 parent respondents, 173 (97%) were mothers, 107 (59.4%) were non-Hispanic White, and 127 (69.5%) of the infants were born prematurely. Parents reported significant family impact and greater financial difficulty. Extremely premature infants, lower household income, parent mental health, and lower parental confidence were predictive of greater impacts on family life. CONCLUSION: Parents reported significant family and financial impacts during their infant's hospitalization amid COVID-19. Further studies are needed to guide clinical practice and inform family-supportive resources that can mitigate consequences to family well-being. KEY POINTS: · Impact of infant hospitalization in the context of COVID-19 is largely unknown.. · In a cohort of NICU parents during COVID-19, they reported changes to family life and finances.. · Greater impacts were reported by parents with lower income, confidence, and very premature infants..

Chinese and global burdens of gastric cancer from 1990 to 2019.

BACKGROUND: Gastric cancer is a common cancer in China. This project investigated the disease burden of gastric cancer from 1990 to 2019 in China and globally. METHODS: The global age-standardized rates (ASRs) were extracted from the Global Burden of Disease. Moreover, the estimated annual percentage changes (eAPCs) in the ASRs of incidence (ASIR), mortality (ASMR), and disability-adjusted life-years (DALYs) were calculated to determine the trends by countries and regions. RESULTS: In China, the ASIR declined from 37.56 to 30.64 per 100,000 and the ASMR declined from 37.73 to 21.72 per 100,000. The global ASIR decreased from 22.44 to 15.59 and the ASMR declined from 20.48 to 11.88 per 100,000 persons from 1990 to 2019. The ASIR was the lowest in Malawi (3.28 per 100,000) and the highest in Mongolia (43.7 per 100,000), whereas the ASMR was the lowest in the United States of America (3.40 per 100,000) and the highest in Mongolia (40.04 per 100,000) in 2019. The incidence of early-onset gastric cancer increased in China. The DALYs attributed to gastric cancer presented a slight decrease during the period. China had a higher mortality/incidence ratio (0.845) and 5-year prevalence (27.6/100,000) than most developed countries. CONCLUSION: China presented a steady decline in the incidence and mortality rates for gastric cancer. The global ASIR, ASMR, and DALYs showed a slight rise decrease. Different patterns of gastric cancer rates and temporal trends have been identified in different geographical regions, indicating that specific strategies are needed to prevent the increase in some countries.