MEG3 in hematologic malignancies: from the role of disease biomarker to therapeutic target.

Maternally expressed gene 3 ( MEG3 ) is a noncoding RNA that is known as a tumor suppressor in solid cancers. Recently, a line of studies has emphasized its potential role in hematological malignancies in terms of tumorigenesis, metastasis, and drug resistance. Similar to solid cancers, MEG3 can regulate various cancer hallmarks via sponging miRNA, transcriptional, or posttranslational regulation mechanisms, but may regulate different key elements. In contrast with solid cancers, in some subtypes of leukemia, MEG3 has been found to be upregulated and oncogenic. In this review, we systematically describe the role and underlying mechanisms of MEG3 in multiple types of hematological malignancies. Particularly, we highlight the role of MEG3 in drug resistance and as a novel therapeutic target.

The impact of COVID-19 prevention and control policy adjustment on anxiety, depression and coping behavior in China: a cross-sectional online survey, 21-28 December, 2022.

BACKGROUND: Following external situation reports, individuals perceive risks, experience different emotional reactions, and further change their behaviors. Therefor people's psychology will also be affected by adjustment of COVID-19 epidemic prevention and control policy, but it remains unknown what kind of coping behaviors will be produced due to psychology. This study defines coping behavior as "medical behavior and irrational consumption behavior after the adjustment of COVID-19 epidemic prevention and control policy in China", assesses the prevalence of negative emotions in the Chinese population after policy adjustments, and explores how negative emotions affect people's coping behaviors, conducts baseline research, provides references and suggestions for policy formulation. METHODS: A cross-sectional online survey was conducted during 21-28 December 2022, included sociodemographic characteristics, COVID-19 infection and irrational purchase behavior, psychological assessment, and opinion polling. Depression and anxiety status are assessed by PHQ-9 and GAD-7. The relationship between anxiety, depression and coping behavior was analyzed by Pearson χ2 test, Fisher's exact test and logistic regression. RESULTS: A total of 3995 infected participants were included in this study, of which 2363(59.1%) and 1194(29.9%) had depression and anxiety. There was a significant difference in clinical treatment and irrational purchase behavior between different level of depression and anxiety. Depression was a risk factor for self- medication (OR = 1.254), seeking professional treatment (OR = 1.215), using online services of medical institutions (OR = 1.320), large-scale purchases of medicines (OR = 1.154) and masks (OR = 1.096). Anxiety was a risk factor for seeking professional treatment (OR = 1.285) and large-scale purchases of masks (OR = 1.168). CONCLUSION: After the adjustment of COVID-19 epidemic prevention and control policy, patient risk perception can increase depression and anxiety. We found that associated with depression, COVID-19 patients are more likely to have medical behaviors such as self- medication, seeking professional treatment, using online services of medical institutions, and storage behaviors of medicines and masks; and anxiety associated with the coping behavior of patients to seek professional treatment and store masks in large quantities. We should improve people's mental health, and on the other hand, we should give people effective psychological education during the epidemic. Therefore, we should set up psychological outpatient clinics in community health institutions, expanding mental health screening and guidance; relying on the psychological outpatient clinic, establish groups of people with depression or anxiety to carry out COVID-19 health education and peer education, to reduce adverse drug reactions, avoid panic seeking professional treatment and irrational purchase behavior, and protect public mental health. TRIAL REGISTRATION: This study has been approved by the Medical Ethics Committee of Capital Medical University (2023SY086), and informed consent was obtained from the study subjects before the investigation.

Research on Error Correction Technology in Underwater SINS/DVL Integrated Positioning and Navigation.

Underwater vehicles are key carriers for underwater inspection and operation tasks, and the successful implementation of these tasks depends on the positioning and navigation equipment with corresponding accuracy. In practice, multiple positioning and navigation devices are often combined to integrate the advantages of each equipment. Currently, the most common method for integrated navigation is combination of the Strapdown Inertial Navigation System (SINS) and Doppler Velocity Log (DVL). Various errors will occur when SINS and DVL are combined together, such as installation declination. In addition, DVL itself also has errors in the measurement of speed. These errors will affect the final accuracy of the combined positioning and navigation system. Therefore, error correction technology has great significance for underwater inspection and operation tasks. This paper takes the SINS/DVL integrated positioning and navigation system as the research object and deeply studies the DVL error correction technology in the integrated system.

Alternative end-joining in BCR gene rearrangements and translocations.

Programmed DNA double-strand breaks (DSBs) occur during antigen receptor gene recombination, namely V(D)J recombination in developing B lymphocytes and class switch recombination (CSR) in mature B cells. Repair of these DSBs by classical end-joining (c-NHEJ) enables the generation of diverse BCR repertoires for efficient humoral immunity. Deletion of or mutation in c-NHEJ genes in mice and humans confer various degrees of primary immune deficiency and predisposition to lymphoid malignancies that often harbor oncogenic chromosomal translocations. In the absence of c-NHEJ, alternative end-joining (A-EJ) catalyzes robust CSR and to a much lesser extent, V(D)J recombination, but the mechanisms of A-EJ are only poorly defined. In this review, we introduce recent advances in the understanding of A-EJ in the context of V(D)J recombination and CSR with emphases on DSB end processing, DNA polymerases and ligases, and discuss the implications of A-EJ to lymphoid development and chromosomal translocations.

LncRNA TUG1 reduces inflammation and enhances insulin sensitivity in white adipose tissue by regulating miR-204/SIRT1 axis in obesity mice.

Prevalence of obesity becomes an important health issue worldwide, but the management of obesity remains unsatisfied. This study aimed to explore the mechanism of long non-coding RNA TUG/miR-204/SIRT1 axis, which was involved in the pathogenesis of obesity. Obesity mouse model was induced by high-fat diet and treated with taurine upregulated gene1 (TUG1) virus via tail intravenous injection. Then, body weight, serum glucose, insulin tolerance, testicular fat weight were detected, as well as the expression of TUG1, microRNA-204 (miR-204), sirtuin1 (SIRT1), and inflammation and fatty accumulation associated proteins and cytokines. Regulatory relationship between TUG1/SIRT1 and miR-204 was confirmed by dual-luciferase reporter activity assay. A high-glucose-induced 3T3-L1 cell model was also constructed to explore the regulatory mechanism of TUG/miR-204/SIRT1 axis in the pathogenesis of obesity at cell level after altering the expression of TUG1, miR-204, and SIRT1. Overexpression of TUG1 could significantly attenuate the weight, serum glucose, glucose, insulin tolerance, fatty accumulation, and inflammation in obesity mice, as well as the elevation of miR-204, but increase the expression of SIRT1, phosphorylated AKT (p-AKT), glucose transporter4 (GLUT4), and peroxisome proliferator activated receptorγ (PPARγ). Both TUG1 and SIRT1 were targets of miR-204 and could be negatively regulated by miR-204. Overexpression of TUG1 could suppress the inflammation in adipocytes via downregulating miR-204 and promote GLUT4/PPARγ/AKT pathway high-glucose-induced inflammation in 3T3-L1 cells. miR-204 inhibitors could also suppress high-glucose-induced inflammation in 3T3-L1 cells via promoting SIRT1/ GLUT4/PPARγ/AKT pathway. LncRNA TUG1 could negatively regulate miR-204 to alleviate inflammation and insulin tolerance via promoting SIRT1/GLUT4/PPARγ/AKT pathway.

LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.

Endosomal sorting complexes required for transport III (ESCRT-III) proteins have been implicated in sealing the nuclear envelope in mammals, spindle pole body dynamics in fission yeast, and surveillance of defective nuclear pore complexes in budding yeast. Here, we report that Lem2p (LEM2), a member of the LEM (Lap2-Emerin-Man1) family of inner nuclear membrane proteins, and the ESCRT-II/ESCRT-III hybrid protein Cmp7p (CHMP7), work together to recruit additional ESCRT-III proteins to holes in the nuclear membrane. In Schizosaccharomyces pombe, deletion of the ATPase vps4 leads to severe defects in nuclear morphology and integrity. These phenotypes are suppressed by loss-of-function mutations that arise spontaneously in lem2 or cmp7, implying that these proteins may function upstream in the same pathway. Building on these genetic interactions, we explored the role of LEM2 during nuclear envelope reformation in human cells. We found that CHMP7 and LEM2 enrich at the same region of the chromatin disk periphery during this window of cell division and that CHMP7 can bind directly to the C-terminal domain of LEM2 in vitro. We further found that, during nuclear envelope formation, recruitment of the ESCRT factors CHMP7, CHMP2A, and IST1/CHMP8 all depend on LEM2 in human cells. We conclude that Lem2p/LEM2 is a conserved nuclear site-specific adaptor that recruits Cmp7p/CHMP7 and downstream ESCRT factors to the nuclear envelope.

Gender Disparity in the Relationship between Prevalence of Thyroid Nodules and Metabolic Syndrome Components: The SHDC-CDPC Community-Based Study.

The study is aimed to investigate the pathogenesis underlying the increased prevalence of thyroid nodule (TN) in different levels of metabolic syndrome (MetS) components and analyze the relationships between TN and MetS components. A total of 6,798 subjects, including 2201 patients with TN, were enrolled in this study. Anthropometric, biochemical, thyroid ultrasonographic, and other metabolic parameters were all measured. There was obviously sexual difference in the prevalence of TN (males 26.0%, females 38.5%, resp.). The prevalence of TN in hyperuricemia (45.7% versus 37.4%, P = 0.001), NAFLD (41.2% versus 36.4%, P < 0.05), and MetS (41.4% versus 35.4%, P < 0.001) groups was significantly increased only in females. Insulin resistance [OR = 1.31 (1.15, 1.49)], MetS [OR = 1.18 (1.03, 1.35)], and diabetes [OR = 1.25 (1.06, 1.48)] were all independent risk factors for TN in total subjects, whereas, after stratified analysis of gender, MetS [OR = 1.29, (1.09, 1.53)] and diabetes [OR = 1.47, (1.17, 1.84)] are still strongly and independently associated with the higher risks of TN in female subjects, but not in males. Our results suggest that the components of MetS might associate with the higher risks of TN in women than in men, but further cohort study of this gender disparity in the association between TN and MetS is required.

Utilizing Group Model Building to Identify Barriers and Facilitators of Hypertension Management in Primary Health Care, China.

Purpose: Group Model Building (GMB) is a qualitative method that refers to a participatory process. This project aims to identify barriers and facilitators of hypertension management in primary health care in China, through which, the leverage point for intervention may be found. Methods: The GMB was used to identify the factors influencing hypertension management. Graphs over time and causal loop diagram (CLD) were main tools of GMB. To propose the influencing factors, key stakeholders were invited to participate in a workshop. During the workshop, stakeholders were encouraged to plot the graphs over time of the variables about research issues and give a descriptive explanation. And based on this, a CLD was initially developed to establish a model of the interaction of factors. After the workshop, the research group further improved the CLD through repeated mutual discussions, and gave feedback to the participants. The Vensim PLE 9.0 software package was used to build CLD. Results: A total of 14 key stakeholders were invited to participate in the workshop. Finally, 26 influencing factors were identified, which were divided into three dimensions, including the institutional, the community health workers (CHWs), and the patient level. And 5 reinforcing loops and 4 balancing loops were formed in the CLD. Promoting the building of the Medical Community/Regional Medical Association, implementing the family doctor contract service (FDCS), and enhancing the motivation of CHWs may be potential leverage points for hypertension management in China. Conclusion: By using GMB, we have identified key factors in the management of hypertension in primary health care and provided comprehensive suggestions to overcome the obstacles.

Home-Based Medical Care Service Motivation Among Medical Staff in Beijing, China: the Role of Institutional Support.

Background: Home-based medical care services (HMCS) play a crucial role in China's response to an aging population. Given the scarcity of quantitative research on motivating medical staff in relevant institutions, this study aimed to explore the impact of institutional support on motivating the provision of HMCS. Methods: The medical staff involved in this study originated from seven community health service centers in Beijing. We utilized a self-designed questionnaire to conduct the survey, gathering socioeconomic information, institutional support for service delivery, as well as the frequency and types of services the respondents provided. Statistical analysis involved the one-way tests and multivariate regressions, and structural equation modeling (SEM) was employed to enhance the results obtained from the regression analysis. Results: A total of 673 valid questionnaires were considered, with 66.12% of respondents indicating their involvement in offering HMCS services and 51.86% reporting the provision of home-based treatment and care services. Upon adjusting for all covariates, multiple regression results highlighted that the establishment of a clear service pathway significantly influenced the motivation to provide services. Furthermore, the results obtained from SEM validated the findings derived from the regression analysis. Conclusion: Standardized institutional support is an essential means of bolstering the motivation of medical staff to provide HMCS and deserves heightened attention from health administrators.

Independent associations of education, intelligence, and cognition with gastrointestinal diseases and the mediating effects of risk factors: a Mendelian randomization study.

Background: Education, intelligence and cognition affect occupational performance and socioeconomic status and may influence virous diseases development. However, the impact of these factors on gastrointestinal diseases and their mediating risk factors remains unclear. Methods: We utilized genome-wide association studies from European ancestry populations to perform two-sample Mendelian randomization analyses, aiming to estimate genetic instruments associated with education, intelligence, or cognition in relation to 24 gastrointestinal diseases Subsequently, we evaluated 14 potential mediators of this association and calculated the corresponding mediated proportions through two-step Mendelian randomization analyses. Result: As the dominant factor in gastrointestinal diseases, education had a statistically significant association with 2 gastrointestinal diseases (acute pancreatitis, gastroesophageal reflux) and a suggestive association with 6 diseases (cirrhosis, alcoholic liver disease, cholecystitis, cholelithiasis, chronic gastritis and gastric ulcer). Of the 14 mediators, smoking and adiposity traits played a major role in mediating the effects. Conclusion: The study demonstrated the causal, independent impact of education on specific gastrointestinal diseases. Smoking and adiposity traits emerged as primary mediators, illuminating potential avenues for targeted interventions for prevention of them.