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Abstract Objective This study aims to establish EQ-5D-Y-3L population norms in Jiangsu, China by conducting a large-scale cross-sectional survey. Methods Children and adolescents aged 9–17 from three cities of Jiangsu Province were selected by multistage stratified random sampling to complete the EQ-5D-Y-3L instrument independently. Population norms for Jiangsu, China were determined by calculating statistics based on age and gender. Logistic and Tobit regression models were employed to explain the relationship between HRQoL and factors such as sociodemographic characteristics/recent acute symptoms (experienced fever/cough/sore throat/diarrhea in the past two weeks). Results Three cities yielded 37,574 valid samples (a sample validity rate of 95.4%). The EQ-5D-Y-3L utility values (mean ± SD) were 0.964 ± 0.085 for males and 0.958 ± 0.077 for females. Males scored 85.94 ± 19.62 and females scored 84.83 ± 18.45 on the VAS (mean ± SD), while the percentages of respondents reporting full health ranged from 58.3 to 78.8%. The dimension in which most respondents reported having no problems was “feeling worried, sad, or unhappy” (23.0%). And the lowest HRQoL was shown in the 14-year-old age group. Gender, age, board at school, and BMI were found to have an association with HRQoL. In addition, recent acute symptoms also correlate with some aspects of HRQoL. Conclusions This study established EQ-5D-Y-3L population norms in Jiangsu, China for the first time. These norms will support resource allocation decision-making and be used as a reference for health evaluation studies.

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

Abstract Risk classification in pediatric acute myeloid leukemia (P-AML) is crucial for personalizing treatments. Thus, we aimed to establish a risk-stratification tool for P-AML patients and eventually guide individual treatment. A total of 256 P-AML patients with accredited mRNA-seq data from the TARGET database were divided into training and internal validation datasets. A gene-expression-based prognostic score was constructed for overall survival (OS), by using univariate Cox analysis, LASSO regression analysis, Kaplan–Meier (K-M) survival, and multivariate Cox analysis. A P-AML-5G prognostic score bioinformatically derived from expression levels of 5 genes (ZNF775, RNFT1, CRNDE, COL23A1, and TTC38), clustered P-AML patients in training dataset into high-risk group (above optimal cut-off) with shorter OS, and low-risk group (below optimal cut-off) with longer OS (p 3, p

Abstract Background The prevalence of abnormal weight is on the rise, presenting serious health risks and socioeconomic problems. Nonetheless, there is a lack of studies on the medical cost savings that can be attained through the mitigation of abnormal weight. The aim of this study was to estimate the impact of abnormal weight on healthcare costs in China. Methods The study employed a 4-wave panel data from China Family Panel Studies (CFPS) between 2012 and 2018 (11,209 participants in each wave). Inpatient, non-inpatient and total healthcare costs were outcome variables. Abnormal weight is categorized based on body mass index (BMI). Initially, the two-part model was employed to investigate the impact of overweight/obesity and underweight on healthcare utilisation and costs, respectively. Subsequently, the estimated results were utilised to calculate the overweight/obesity attributable fraction (OAF) and the underweight attributable fraction (UAF). Results In 2018, healthcare costs per person for overweight and obese population were estimated to be $607.51 and $639.28, respectively, and the underweight population was $755.55. In comparison to people of normal weight, individuals who were overweight/obese (OR = 1.067, p

Abstract Approximately 30% of lymphomas occur outside the lymph nodes, spleen, or bone marrow, and the incidence of extranodal lymphoma has been rising in the past decade. While traditional chemotherapy and radiation therapy can improve survival outcomes for certain patients, the prognosis for extranodal lymphoma patients remains unsatisfactory. Extranodal lymphomas in different anatomical sites often have distinct cellular origins, pathogenic mechanisms, and clinical manifestations, significantly influencing their diagnosis and treatment. Therefore, it is necessary to provide a comprehensive summary of the pathogenesis, diagnosis, and treatment progress of extranodal lymphoma overall and specifically for different anatomical sites. This review summarizes the current progress in the common key signaling pathways in the development of extranodal lymphomas and intervention therapy. Furthermore, it provides insights into the pathogenesis, diagnosis, and treatment strategies of common extranodal lymphomas, including gastric mucosa-associated lymphoid tissue (MALT) lymphoma, mycosis fungoides (MF), natural killer/T-cell lymphoma (nasal type, NKTCL-NT), and primary central nervous system lymphoma (PCNSL). Additionally, as PCNSL is one of the extranodal lymphomas with the worst prognosis, this review specifically summarizes prognostic indicators and discusses the challenges and opportunities related to its clinical applications. The aim of this review is to assist clinical physicians and researchers in understanding the current status of extranodal lymphomas, enabling them to make informed clinical decisions that contribute to improving patient prognosis.

Abstract Background Inequality of opportunity (IOp) stemming from social circumstances exists in outpatient service utilization for the multimorbid elderly in China. However, little is known regarding the magnitude of the IOp and its composition. Therefore, this study aims to measure the IOp in outpatient expenditure and provide potential pathways for policy reform by assessing the contribution of each circumstance. Methods This study included 3527 elderly aged ≥ 65 years with multimorbidity from the Chinese Longitudinal Healthy Longevity Study conducted in 2017–2018. An ordinary least squares regression model was used to analyze the circumstance-influencing factors of outpatient expenditure. The parametric approach was performed to quantify the IOp in outpatient expenditure and the Shapley value decomposition method was employed to determine the contribution of each circumstance. By extracting heterogeneity in the residual of the circumstance-dependent equation of outpatient expenditure across circumstance groups divided based on cluster analysis, we captured the effect of unobserved circumstances. Results Except for pension and distance to health facilities, all the associations between circumstance and outpatient expenditure were statistically significant. The inequality caused by circumstances accounted for 25.18% of the total inequality. The decomposition results revealed that the reimbursement rate contributed 82.92% of the IOp, followed by education duration (4.55%), household registration (3.21%), household income (3.18%), pension (1.49%), medical insurance (1.26%), physical labor (0.99%), unobserved circumstances (0.86%), distance to health facilities (0.83%) and region (0.71%). Conclusions The priority of policy enhancement is to effectively improve the outpatient reimbursement benefit for treating chronic diseases. Additional crucial actions include enhancing the health literacy of the multimorbid elderly to promote the shift from medical needs to demands and accelerating the construction of rural capacity for providing high-quality healthcare to the elderly with multimorbidity.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) – related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy ( P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [ HR ] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 ( HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Noncommunicable chronic diseases among the elderly population represent a significant economic burden in China. However, previous disease-related health cost studies lacked representation of older adults and comparability of the burden of multiple chronic diseases. The objective of this study was to determine the fraction of health care costs attributable to the 6 most prevalent chronic diseases and comorbidities in the sample of older adults. This study employed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), with 3 waves in 2011, 2014, and 2018, and included 18 349 observations in total. Outpatient costs, inpatient costs, and total health care costs were included in this study. Based on a 2-part random effects model, the effect of chronic disease on health service utilization was first explored by constructing a dummy variable for whether or not to utilize health care, followed by estimation of attributable costs in the population with health care utilization. Among the older adults in the sample, hypertension, heart disease, cataracts, arthritis, stroke or Cerebrovascular disease (CVD) and chronic lung disease are the 6 most prevalent chronic conditions. The costs attributable to the 6 chronic diseases mentioned above were 36.00% of outpatient costs, 55.92% of inpatient costs, and 45.05% of total health care costs for older adults. Of these, heart disease, stroke or CVD, and chronic lung disease accounted for 22.11%, 13.24%, and 10.56% of total health care costs, respectively. Moreover, the proportion of health care costs attributable to chronic diseases was higher for older adults who were male, lived in urban areas, and had a lower level of education. The proportion of health care costs attributable to chronic diseases is substantial among older adults in China. Health care costs associated with chronic diseases can be decreased with well-targeted interventions and comprehensive access to health services.

Background: The economic selection hypothesis, which argues that the initial economic situation determines both subsequent health and economic conditions, has been drawn into the debate on causation-selection issues. This study aims to construct a path model with self-rated health and depression score of older adults as health outcomes to measure and compare the social causation forces of wealth accumulation, social selection forces of adulthood health, and economic selection forces of childhood economics, and to examine their gender disparities. Methods: Data was obtained from a sample of 19613 older adults aged 45 years or above from the 2014 life history survey and the 2015 routine follow-up survey of the China Health and Retirement Longitudinal Study. Structural equation modeling analysis was conducted employing the full information maximum likelihood estimation method. Results: The presence of social causation, social selection, and economic selection were all statistically supported. In self-rated health, social selection forces held the dominant position, while social causation forces were comparable to economic selection forces. In depression score, social selection still exhibited stronger forces than economic selection, but social causation had forces close to social selection and greater than economic selection. The forces of the three hypotheses in self-rated health did not significantly change with gender, but social causation exerted mightier forces than economic selection within the male group, unlike the female group. The forces of economic selection in depression score were greater in females than males and no significant differences were observed among the forces of the three hypotheses in the female group. Conclusions: Social causation, social selection, and economic selection operate simultaneously on the self-rated health and depression score of older adults. However, the force magnitudes of the three hypotheses and/or their rankings differ by health outcomes and gender.

AbstractThe chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

Abstract Background Natural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with a poor prognosis and limited therapeutic options. Therefore, there is an urgent need to exploit potential novel therapeutic targets for the treatment of NKTL. Histone deacetylase (HDAC) inhibitor chidamide was recently approved for treating relapsed/refractory peripheral T-cell lymphoma (PTCL) patients. However, its therapeutic efficacy in NKTL remains unclear. Methods We performed a phase II clinical trial to evaluate the efficacy of chidamide in 28 relapsed/refractory NKTL patients. Integrative transcriptomic, chromatin profiling analysis and functional studies were performed to identify potential predictive biomarkers and unravel the mechanisms of resistance to chidamide. Immunohistochemistry (IHC) was used to validate the predictive biomarkers in tumors from the clinical trial. Results We demonstrated that chidamide is effective in treating relapsed/refractory NKTL patients, achieving an overall response and complete response rate of 39 and 18%, respectively. In vitro studies showed that hyperactivity of JAK-STAT signaling in NKTL cell lines was associated with the resistance to chidamide. Mechanistically, our results revealed that aberrant JAK-STAT signaling remodels the chromatin and confers resistance to chidamide. Subsequently, inhibition of JAK-STAT activity could overcome resistance to chidamide by reprogramming the chromatin from a resistant to sensitive state, leading to synergistic anti-tumor effect in vitro and in vivo. More importantly, our clinical data demonstrated that combinatorial therapy with chidamide and JAK inhibitor ruxolitinib is effective against chidamide-resistant NKTL. In addition, we identified TNFRSF8 (CD30), a downstream target of the JAK-STAT pathway, as a potential biomarker that could predict NKTL sensitivity to chidamide. Conclusions Our study suggests that chidamide, in combination with JAK-STAT inhibitors, can be a novel targeted therapy in the standard of care for NKTL. Trial registration: ClinicalTrials.gov, NCT02878278. Registered 25 August 2016, https://clinicaltrials.gov/ct2/show/NCT02878278

Abstract Extensive clinical and experimental evidence suggests that macrophages play a crucial role in cancer immunotherapy. Cluster of differentiation (CD) 47, which is found on both healthy and malignant cells, regulates macrophage-mediated phagocytosis by sending a "don't eat me" signal to the signal regulatory protein alpha (SIRPα) receptor. Increasing evidence demonstrates that blocking CD47 interaction with SIRPα can enhance cancer cell clearance by macrophages. Additionally, inhibition of CD47/SIRPα interaction can increase antigen cross-presentation, leading to T-cell priming and an activated adaptive antitumor immune response. Therefore, inhibiting CD47/SIRPα axis has a significant impact on tumor immunotherapy. Studies on CD47 monoclonal antibodies are at the forefront of research, and impressive results have been obtained. Nevertheless, hematotoxicity, especially anemia, has become the most common adverse effect of the CD47 monoclonal antibody. More specific targeted drugs (i.e., bispecific antibodies, SIRPα/Fc fusion protein antibodies, and small-molecule inhibitors) have been developed to reduce hematotoxicity. Here, we review the present usage of CD47 antagonists for the treatment of lymphomas and hematologic neoplasms from the perspectives of structure, function, and clinical trials, including a comprehensive overview of the drugs in development.

Abstract Background Unhealthy gestational weight gain is a modifiable risk factor for adverse maternal and child health. Appropriate and effective intervention strategies that focus on behavioral change or maintenance are critical in weight management during pregnancy. Our aim was to uncover the influencing factors and psychosocial mechanisms of gestational weight control behavior, and to construct a behavioral model suitable for intervention based on Information-Motivation-Behavioral skills (IMB) model. Methods A sample of 559 pregnant women from a municipal maternal and child healthcare facility in Jiangsu Province, China was enrolled in this cross-sectional empirical study. Partial least square structural equation modelling was used to verify the hypothesized model, and post hoc analyses was used to test the effect of parity and pre-pregnancy BMI on the model. Results The IMB model elements can predict gestational weight management (GWM) behavior well, with information being the most influential factor. As predicted, information affects GWM directly (β = 0.325, p

Abstract Programmed cell death protein 1(PD-1) is a type of immune-inhibitory checkpoint protein, which delivers inhibitory signals to cytotoxic T cells by binding to the programmed death ligand-1 (PD-L1) displayed on the surface of cancer cells. Antibodies blocking PD-1/PD-L1 interaction have been extensively used in treatment of human malignancies and have achieved promising outcomes in recent years. However, gradual development of resistance to PD-1/PD-L1 blockade has decreased the effectiveness of this immunotherapy in cancer patients. The underlying epigenetic mechanisms need to be elucidated for application of novel strategies overcoming this immunotherapy resistance. Epigenetic aberrations contribute to cancerogenesis by promoting different hallmarks of cancer. Moreover, these alterations may lead to therapy resistance, thereby leading to poor prognosis. Recently, the epigenetic regulatory drugs have been shown to decrease the resistance to PD-1/PD-L1 inhibitors in certain cancer patients. Inhibitors of the non-coding RNAs, DNA methyltransferases, and histone deacetylases combined with PD-1/PD-L1 inhibitors have shown considerable therapeutic efficacy against carcinomas as well as blood cancers. Importantly, DNA methylation-mediated epigenetic silencing can inhibit antigen processing and presentation, which promotes cancerogenesis and aggravates resistance to PD-1/PD-L1 blockade immunotherapy. These observations altogether suggest that the combination of the epigenetic regulatory drugs with PD-1/PD-L1 inhibitors may present potential solution to the resistance caused by monotherapy of PD-1/PD-L1 immunotherapy.

ObjectThere is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms.MethodsGSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions.ResultsBetween the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software’s MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p.ConclusionOur research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD.

Invasion success of clonal plants is closely related to their unique clonal life history, and clonal division of labor is a crucial clonal trait. However, so far, it is unclear whether invasive alien clonal species generally possess a greater capacity for division of labor than native species and whether this pattern is affected by environmental conditions. To test whether patch contrast affects the differences in the capacity for division of labor between invasive alien and native clonal plants, we selected five pairs of exotic invasive and native clonal plant species that are congeneric and co-occurring in China as experimental materials. We grew the clonal fragment pairs of these invasive and native plants under high, low, or no contrast of reciprocal patchiness of light and nutrient, respectively, with ramet connections either severed (division of labor prevented) or kept intact (division of labor allowed). The results showed that connection significantly decreased the proportion of biomass allocated to roots in distal (younger) ramets, whereas it increased in proximal (older) ramets of all studied plants under high -contrast treatments. This clear pattern strongly indicated the occurrence of division of labor. Furthermore, the connection had a more pronounced effect on the pattern of biomass allocation of invasive alien plants, resulting in a greater increase in biomass for invasive alien plants compared to native plants. These findings suggest that the invasive alien plants possess a greater capacity for division of labor, which may confer a competitive advantage to them over natives, thus facilitating their invasion success in some heterogeneous habitats such as forest edges where light and soil nutrients show a high negative correlation.

Abstract Metastasis is the leading cause of cancer-related death. The interactions between circulating tumor cells and endothelial adhesion molecules in distant organs is a key step during extravasation in hematogenous metastasis. Surgery is a common intervention for most primary solid tumors. However, surgical trauma-related systemic inflammation facilitates distant tumor metastasis by increasing the spread and adhesion of tumor cells to vascular endothelial cells (ECs). Currently, there are no effective interventions to prevent distant metastasis. Here, we show that HECTD3 deficiency in ECs significantly reduces tumor metastasis in multiple mouse models. HECTD3 depletion downregulates expression of adhesion molecules, such as VCAM-1, ICAM-1 and E-selectin, in mouse primary ECs and HUVECs stimulated by inflammatory factors and inhibits adhesion of tumor cells to ECs both in vitro and in vivo. We demonstrate that HECTD3 promotes stabilization, nuclear localization and kinase activity of IKKα by ubiquitinating IKKα with K27- and K63-linked polyubiquitin chains at K296, increasing phosphorylation of histone H3 to promote NF-κB target gene transcription. Knockout of HECTD3 in endothelium significantly inhibits tumor cells lung colonization, while conditional knockin promotes that. IKKα kinase inhibitors prevented LPS-induced pulmonary metastasis. These findings reveal the promotional role of the HECTD3-IKKα axis in tumor hematogenous metastasis and provide a potential strategy for tumor metastasis prevention.

Abstract Background Methamphetamine (METH) abuse causes serious health problems, including injury to the immune system, leading to increased incidence of infections and even making withdrawal more difficult. Of course, immune cells, an important part of the immune system, are also injured in methamphetamine abuse. However, due to different research models and the lack of bioinformatics, the mechanism of METH injury to immune cells has not been clarified. Methods We examined the response of three common immune cell lines, namely Jurkat, NK-92 and THP-1 cell lines, to methamphetamine by cell viability and apoptosis assay in vitro, and examined their response patterns at the mRNA level by RNA-sequencing. Differential expression analysis of two conditions (control and METH treatment) in three types of immune cells was performed using the DESeq2 R package (1.20.0). And some of the differentially expressed genes were verified by qPCR. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes by the clusterProfiler R package (3.14.3). And gene enrichment analysis was also performed using MetaScape ( www.metascape.org ). Results The viability of the three immune cells was differentially affected by methamphetamine, and the rate of NK-cell apoptosis was significantly increased. At the mRNA level, we found disorders of cholesterol metabolism in Jurkat cells, activation of ERK1 and ERK2 cascade in NK-92 cells, and disruption of calcium transport channels in THP-1 cells. In addition, all three cells showed changes in the phospholipid metabolic process. Conclusions The results suggest that both innate and adaptive immune cells are affected by METH abuse, and there may be commonalities between different immune cells at the transcriptome level. These results provide new insights into the potential effects by which METH injures the immune cells.

Abstract Background The prevalence of excessive gestational weight gain (EGWG) during pregnancy is increasing, and it is extremely harmful to pregnant women and newborns. Previous studies have suggested that EGWG is associated with various factors. We conducted a systematic review and meta-analysis to identify, quantify and analyze determinants of EGWG and evaluate the effect of these determinants on EGWG. Methods We searched for articles, from January 2009 to November 2020, related to the determinants of EGWG during pregnancy using four Chinese and four English databases. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was utilized to guide the systematic review and meta-analysis process. Results Seventy studies, which identified EGWG factors in pregnant women (58 factors, 3 themes: individual [7 aspects, 37 factors]; family [4 aspects, 8 factors]; and social [4 aspects, 13 factors]), were included and analyzed in the systematic review. A meta-analysis was conducted for 13 factors (including 10 individual factors, 2 family factors, and 1 social factor) and revealed that pre-pregnancy overweight (including obesity), younger age (≤ 30 years old), unemployed, primiparity, smoking, and being unmarried (including divorced) were risk factors for EGWG, while prepregnancy underweight and inadequate antenatal care were protective factors for EGWG. There was no significant correlation between EGWG and education level, alcohol consumption, planning pregnancy, food security, and whether access to nutrition guidance during pregnancy. Conclusions EGWG was prevalent in pregnant women, and its prevalence seemed to be high and similar in many countries. Based on observational studies with medium-level and high-level evidence, some individual, family, and social factors were found to be associated with EGWG using qualitative and quantitative methods. In the future, exposure of pregnant women to risk factors for EGWG should be avoided, and interventions should be developed around the identified factors.

Abstract The combination of immune checkpoint blockade (ICB) with chemotherapy significantly improves clinical benefit of cancer treatment. Since chemotherapy is often associated with adverse events, concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination therapy. However, whether these ancillary drugs could impede immunotherapy remains unknown. Here, we showed that ∆9-tetrahydrocannabinol (THC), the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea, reduced the therapeutic effect of PD-1 blockade. The endogenous cannabinoid anandamide (AEA) also impeded antitumor immunity, indicating an immunosuppressive role of the endogenous cannabinoid system (ECS). Consistently, high levels of AEA in the sera were associated with poor overall survival in cancer patients. We further found that cannabinoids impaired the function of tumor-specific T cells through CNR2. Using a knock-in mouse model expressing a FLAG-tagged Cnr2 gene, we discovered that CNR2 binds to JAK1 and inhibits the downstream STAT signaling in T cells. Taken together, our results unveiled a novel mechanism of the ECS-mediated suppression on T-cell immunity against cancer, and suggest that cannabis and cannabinoid drugs should be avoided during immunotherapy.

Pancreatic cancer (PC) is a malignant tumor with high malignancy that is difficult to diagnose and treat. PC is a major medical problem because of its low early diagnosis rate, high surgical mortality rate, low cure rate, and expensive related testing cost. Therefore, the significance of finding new markers for PC is self-evident. Semaphorins (Semas) have been shown to affect angiogenesis and lymphangiogenesis and can also directly affect the behavior of tumor cells. The expression and related action targets of its family members on PC are summarized in this review.

Macrophage inflammation promotes insulin resistance during diet-induced obesity. Here the authors show that macrophage NOC4L is decreased in humans and mice with obesity, that macrophage NOC4L deficiency aggravated high-fat diet induced inflammation and insulin resistance, and that NOC4L interacts with toll-like receptor 4, to inhibit endocytosis, and thus blocks TLF4/TRIF inflammatory signaling.

Abstract Glioma represents a fast proliferating and highly invasive brain tumor which is resistant to current therapies and invariably recurs. Despite some advancements in anti-glioma therapies, patients’ prognosis remains poor. Toll-like receptors (TLRs) act as the first line of defense in the immune system being the detectors of those associated with bacteria, viruses, and danger signals. In the glioma microenvironment, TLRs are expressed on both immune and tumor cells, playing dual roles eliciting antitumoral (innate and adaptive immunity) and protumoral (cell proliferation, migration, invasion, and glioma stem cell maintenance) responses. Up to date, several TLR-targeting therapies have been developed aiming at glioma bulk and stem cells, infiltrating immune cells, the immune checkpoint axis, among others. While some TLR agonists exhibited survival benefit in clinical trials, it attracts more attention when they are involved in combinatorial treatment with radiation, chemotherapy, immune vaccination, and immune checkpoint inhibition in glioma treatment. TLR agonists can be used as immune modulators to enhance the efficacy of other treatment, to avoid dose accumulation, and what brings more interests is that they can potentiate immune checkpoint delayed resistance to PD-1/PD-L1 blockade by upregulating PD-1/PD-L1 overexpression, thus unleash powerful antitumor responses when combined with immune checkpoint inhibitors. Herein, we focus on recent developments and clinical trials exploring TLR-based treatment to provide a picture of the relationship between TLR and glioma and their implications for immunotherapy.

Abstract Objectives The aim of this study is to address the difficulties encountered by public health workers in the early and middle stages of their efforts to combat COVID-19, compare the gaps among different types of institutions, and identify shortcomings in epidemic control. Methods Using multi-stage sampling, a survey of public health workers involved in the prevention and control of COVID-19 was conducted from 18 February to 1 March 2020 through a self-administered questionnaire. These public health workers were from the primary health care center (defined as “primary-urban” and “primary-rural” for those in urban and rural areas, respectively) and the center for disease control and prevention (defined as “non-primary”) in five provinces including Hubei, Guangdong, Sichuan, Jiangsu and Gansu, China. Results A total of 9,475 public health workers were surveyed, of which 40.0 %, 27.0 % and 33.0 % were from the primary-rural, primary-urban and non-primary, respectively. The resources shortage were reported by 27.9 % participants, with the primary-rural being the worst affected (OR = 1.201, 95 %CI: 1.073–1.345). The difficulties in data processing were reported by 31.5 % participants, with no significant differences among institutions. The difficulties in communication and coordination were reported by 29.8 % participants, with the non-primary being the most serious (primary-rural: OR = 0.520, 95 %CI: 0.446–0.606; primary-urban: OR = 0.533, 95 %CI: 0.454–0.625). The difficulties with target audiences were reported by 20.2 % participants, with the primary-urban being the worst (OR = 1.368, 95 %CI: 1.199–1.560). The psychological distress were reported by 48.8 % participants, with no significant differences among institutions. Conclusions Psychological distress is the most serious problem in the prevention and control of COVID-19. Resources shortage in primary-rural, difficulties in communication and coordination in non-primary, and difficulties with target audiences in the primary-urban deserve attention. This study will provide scientific evidences for improving the national public health emergency management system, especially for reducing the urban-rural differences in emergency response capacity.

An undesirable psychological state may deteriorate individual's weight management-related behaviors. This study aims to see if ineffective weight control measures were linked to depressive symptoms during pregnancy. We conducted a cross-sectional questionnaire survey of 784 pregnant women and collected information on sociodemographic factors, maternal characteristics, depression, and weight management activities throughout pregnancy (exercise management, dietary management, self-monitoring regulation, and management objectives). About 17.5% of pregnant women exhibited depressive symptoms. The mean score on dietary management was upper-middle, exercise management and self-monitoring regulation were medium, and management objectives were lower-middle. Multivariable linear regression analysis revealed that pregnant women with depressive symptoms had lower levels of exercise management (β = −1.585, p = 0.005), dietary management (adjusted β = −0.984, p = 0.002), and management objectives (adjusted β = −0.726, p = 0.009). However, there was no significant relationship between depressive symptoms and pregnant women's self-monitoring regulating behavior (p > 0.05). The findings indicated the inverse association between depressive symptoms and gestational weight management behaviors. These results offer important indications for pregnancy weight management professionals by highlighting the need for mental health interventions for pregnant women experiencing depressive symptoms.

Background: The prognostic roles of ferroptosis-related mRNAs (FG) and lncRNAs (FL) in pediatric acute myeloid leukemia (P-AML) patients remain unclear.Methods: RNA-seq and clinical data of P-AML patients were downloaded from the TARGET project. Cox and LASSO regression analyses were performed to identify FG, FL, and FGL (combination of FG and FL) prognostic models, and their performances were compared. Tumor microenvironment, functional enrichment, mutation landscape, and anticancer drug sensitivity were analyzed.Results: An FGL model of 22 ferroptosis-related signatures was identified as an independent parameter, and it showed performance better than FG, FL, and four additional public prognostic models. The FGL model divided patients in the discovery cohort (N = 145), validation cohort (N = 111), combination cohort (N = 256), and intermediate-risk group (N = 103) defined by the 2017 European LeukemiaNet (ELN) classification system into two groups with distinct survival. The high-risk group was enriched in apoptosis, hypoxia, TNFA signaling via NFKB, reactive oxygen species pathway, oxidative phosphorylation, and p53 pathway and associated with low immunity, while patients in the low-risk group may benefit from anti-TIM3 antibodies. In addition, patients within the FGL high-risk group might benefit from treatment using SB505124_1194 and JAK_8517_1739.Conclusion: Our established FGL model may refine and provide a reference for clinical prognosis judgment and immunotherapies for P-AML patients.

BackgroundThe national essential public health service (NEPHS) has been in operation for more than a decade. Numerous studies examined the utilization of NEPHS by migrants and the factors that influence it, but few examined the effect of NEPHS awareness and utilization on the health of inhabitants, particularly migrants. The purpose of this study is to ascertain the level of awareness and utilization of NEPHS, as well as to examine their health-improving effects on migrants.MethodsBased on the data from the 2017 China Migrants Dynamic Survey, linear probability model, ordered logit model and the propensity score matching methods were employed to investigate impact of awareness and utilization of NEPHS on the health among Chinese migrants. Mediating effect model were used to identify the mechanism of the impact of NEPHS on health.ResultsThe findings indicated that migrants' awareness and utilization of NEPHS are still insufficient. After adjusting for other factors, the study discovered that increased awareness and use of NEPHS had a beneficial influence on migrants' self-rated health. Further heterogeneity analysis revealed significant disparities in the health consequences of NEPHS awareness and utilization across subgroups. The effect of increased awareness and usage of NEPHS on health is stronger for middle-aged and elderly people, women, and low-educated migrants with urban household registration. The estimated results of the mediating effect model supported the mechanism that increased NEPHS awareness among the floating population could encourage its utilization and further improve the floating population's health.ConclusionsGiven that migrants' NEPHS utilization is still low and that NEPHS utilization has a positive effect on health, some targeted strategies, such as a variety of new media communication methods, health education related to occupational disease and tuberculosis prevention, and targeted NEPHS projects for specific groups, such as men, young and middle-aged groups, those with a high level of education, and rural migrants, should be conducted to improve the health of migrants.

Despite advances in treatment, the prognosis for glioma patients remains poor. Bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extraterminal (BET) protein family, plays an important role in controlling oncogene expression and genome stability. In recent years, numerous BRD4 inhibitors have entered clinical trials and achieved exciting results in tumor treatment. Recent clinical studies have shown that BRD4 expression in glioma is significantly higher than in the adjacent normal brain tissue. BRD4 inhibitors effectively penetrate the blood-brain barrier and target glioma tumor tissues but have little effect on normal brain tissues. Thus, BRD4 is a target for the treatment of glioma. In this study, we discuss the progress in the use of BRD4 inhibitors for glioma treatment, their mechanism of action, and their broad potential clinical application.

Abstract Background Poor mental health status and associated risk factors of public health workers have been overlooked during the COVID-19 pandemic. This study used the effort–reward imbalance model to investigate the association between work-stress characteristics (effort, over-commitment, reward) and mental health problems (anxiety and depression) among front-line public health workers during the COVID-19 pandemic in China. Methods A total of 4850 valid online questionnaires were collected through a self- constructed sociodemographic questionnaire, the adapted ERI questionnaire, the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder Scale (GAD-7). Hierarchical logistic regression analysis was conducted to investigate the association between ERI factors and mental health problems (i.e., depression and anxiety), with reward treated as a potential moderator in such associations. Results The data showed that effort and over-commitment were positively associated with depression and anxiety, while reward was negatively associated with depression and anxiety. Development and job acceptance were the two dimensions of reward buffered the harmful effect of effort/over-commitment on depression and anxiety, whereas esteem was non-significant. Conclusions This study confirmed the harmful effects of effort and over-commitment on mental health among public health workers during the COVID-19 pandemic in China. Such effects could be alleviated through an appropriate reward system, especially the development and job acceptance dimensions of such a system. These findings highlight the importance of establishing an emergency reward system, comprising reasonable work-allocation mechanism, bonuses and honorary titles, a continuous education system and better career-development opportunities.

ABSTRACT Background Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. Methods Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results The prevalence of depression, anxiety, and poor self-rated health was 21.3, 19.0, and 9.8%, respectively, among public health workers (27.1, 20.6, and 15.0% among CDC workers and 17.5, 17.9, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p 1 month at the current work intensity (ORm=0.44~0.55, p

Abstract Background The World Health Organization (WHO) in 2015 stated that every effort should be made to provide cesarean delivery (CD) for women in need. In China, the two-child policy largely prompts the number of advanced age childbirth, which raises the possibility of an increasing number of women who need a c-section. The aim of this study was to assess the trends in the overall and medical indication-classified CD rates in the era of the two-child policy in Jiangsu, China. Methods A retrospective cross-sectional study of 291,448 women who delivered in 11 hospitals in Jiangsu province between 2012 and 2019 was conducted. Medical cesarean indication for each woman was ascertained by manually reviewing the medical records. The 291,448 women were divided into two subgroups according to the presence of the indications: the indicated group (7.80%) and the non-indicated group (92.20%). We then fitted joinpoint regression and log-binomial regression models to estimate trends in the CD rates across the study period. Results The overall CD rate was observed with a declining trend from 52.51% in 2012–2015 to 49.76% in 2016–2019 (adjusted RR, 0.92; 95% CI, 0.91–0.93; P

Cardiac resynchronization therapy (CRT) for heart failure requires transvenous insertion of a left ventricular pacing lead through the coronary sinus. However, repeated intraoperative dislocations often occur. Therefore, we describe a novel technique that uses the loop technique to treat patients with repeated intraoperative dislocations during transvenous left ventricular lead implantation to stabilize the lead in its final position. In five patients with repeated intraoperative dislocation during transvenous left ventricular lead implantation, the loop technique was successfully used to stabilize the lead in its final position. The pacing and sensing parameters were satisfactory in all patients at implantation and 12 months post-operatively. Compared with the pre-operative values, the 12-month post-operative values for the left ventricular ejection fraction were significantly increased and the left ventricular end systolic dimension and left ventricular end diastolic dimension were significantly decreased (P < 0.05). The left ventricular ejection fraction of these 5 patients increased by more than 15%. CRT significantly improved the left ventricular structure and function of these 5 patients. During the 1-, 3-, 6-, and 12-month follow-ups, no left ventricular lead dislocations were observed. This loop technique is safe and effective and can be considered for repeated intraoperative dislocation during transvenous left ventricular lead implantation through the coronary sinus of a CRT device.

Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.

Abstract Background This study aimed to understand the association between socioeconomic status (SES) and Health Related Quality of Life (HRQoL) and the contribution of SES to health inequality among Tibetans of agricultural and pastoral areas (APA) in Tibet, China. Methods The data were from Health Survey of Tibetans in APA conducted in 2014. A total of 816 respondents were enrolled for the analysis Multiple linear regression was employed to examine the relationship between SES and HRQoL. Concentration index (CI) was used to measure the degree of health inequality and a Wagstaff-type CI decomposition method was applied to measure the contribution of SES to inequality. Results SES had significant association with HRQoL among the Tibetans in APA. The high SES group was more likely to have a higher Eq-5d index (0.77 vs. 0.67, P

Inappropriate gestational weight gain has become a public health concern that threatens maternal and child health. Pregnant women's ability to manage their weight during pregnancy directly impacts their weight gain. In this study, we integrated the protection motivation theory and the information-motivation-behavioral skills model to develop an integrative theoretical model suitable for pregnancy weight management and reveal significant explainable factors of weight management behaviors during pregnancy. Based on a cross-sectional survey of 550 pregnant women from Jiangsu province, we came up with our findings. The results showed that several factors influenced pregnancy weight management behavior. According to the research, information, self-efficacy, response costs, and behavioral skills were significantly associated with weight management behaviors during pregnancy, while behavioral skills were also significant mediators of information, self-efficacy, and behavior. Furthermore, the information related to pregnancy weight management had the biggest impact on weight management behavior during pregnancy. The results of the model fit were acceptable and the integrative model could explain 30.6% of the variance of weight management behavior during pregnancy, which implies that the integrative theoretical model can effectively explain and predict weight management behaviors during pregnancy. Our study provides practical implications for the integrative model in improving pregnancy weight management behavior and offers a theoretical base for the weight management of pregnant women.