U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression.

BACKGROUND: Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. METHODS: SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. RESULTS: SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. CONCLUSION: U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.

The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

Assessment of Medical Expenditure for Patients With Breast Cancer in China: Evidence From Current Curative Expenditure by System of Health Accounts 2011.

OBJECTIVES: The incidence and mortality of breast cancer have been increasing in China and bring heavy economic burdens to patients, families, and society. This study aimed to analyze the structure and influencing factors of inpatient expenditures of patients with breast cancer and put forward suggestions for insurance management. METHODS: A multistage stratified random sampling method was used to investigate 379 medical institutions and 7366 pieces of inpatient records of patients with breast cancer in Dalian in 2018. Under the framework of "System of Health Accounts 2011," the current curative expenditure (CCE) and its distribution were calculated. The relationships between hospitalization expenditure and factors were analyzed by multiple stepwise regression and structural equation modeling. RESULTS: The CCE of patients with breast cancer in Dalian in 2018 was ¥273.38 million, accounting for 10.66% of the total expenditure on cancer. The majority of the CCE flowed to large general hospitals. The CCE was concentrated in patients aged 40 to 69 years (23.46%). The hospitalization expenditure correlated positively with length of stay, surgery, and drug expenses (rs = 0.586-0.754, P < .01) and negatively associated with age (rs = -0.074, P < .01). The length of stay mediated the relationship between surgery and hospitalization expenses for patients with breast cancer. The factors that affected the hospitalization expenditure were the drug expenses, surgery, length of stay, insurance status, and institution level. CONCLUSIONS: The cost control for CCE of breast cancer inpatient treatment is crucial in China. Promoting hierarchical diagnosis and treatment, reducing the length of stay, and improving medical insurance depth would be effective measures to reduce the financial burden of patients.

Efficacy and safety of PD-1/PD-L1 inhibitors in triple-negative breast cancer: a systematic review and meta-analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis that seriously threatens women's health. There is still a lack of effective therapeutic targets for TNBC treatment. We conducted a meta-analysis to evaluate the efficacy and safety of programmed cell death protein 1 (PD-1)/programmed death protein ligand 1 (PD-L1) inhibitors in combination with chemotherapy for TNBC patients. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) related to PD-1/PD-L1 inhibitors combined with chemotherapy. Literature conforming to the research content was identified according to the inclusion and exclusion criteria. The endpoints of efficacy were pathological complete response (pCR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). Safety outcomes included adverse events (AEs) of any grade, AEs of grade ≥3, serious AEs, and the incidence of various AEs. We obtained odds ratios (OR), hazard ratio (HR), and 95% confidence interval (CI) for the included studies. Data analysis was performed using Review Manager software (version 5.3). RESULTS: A total of 4468 patients from eight RCTs were analyzed. PD-1/PD-L1 inhibitors in combination with chemotherapy significantly improved pCR (OR, 1.59; 95% CI, 1.28 - 1.98, p < 0.0001), EFS (HR, 0.66; 95% CI, 0.48 - 0.91, p = 0.01), and OS (HR, 0.72; 95% CI, 0.52 - 0.99, p = 0.05) in patients with TNBC compared to chemotherapy alone or placebo in combination with chemotherapy. Furthermore, we found that the pCR rate was almost identical in the PD-L1 positive group (OR, 1.65; 95% CI, 1.26 - 2.16, p = 0.0002) and the PD-L1 negative group (OR, 1.56; 95% CI, 1.04 - 2.33, p = 0.03). Among patients with advanced-stage TNBC, PFS (HR, 0.82; 95% CI, 0.74 - 0.90, p < 0.0001) was longer in the combination therapy group than in the chemotherapy group. There were no statistically significant differences between the experimental and control groups in OS (HR, 1.03; 95% CI, 0.74 - 1.42, p = 0.87). In terms of safety, we found that the combination therapy group had a significantly higher incidence of hyperthyroidism in patients with early and advanced TNBC (OR, 5.76; 95% CI, 2.38 - 13.95, p = 0.0001) (OR, 7.86; 95% CI, 2.65 - 23.29, p = 0.0002). CONCLUSIONS: The combination of PD-1/PD-L1 inhibitors and chemotherapy could improve the survival and prognosis of patients with early and advanced TNBC. Combination treatment may be harmful to the thyroid; therefore, active surveillance and regular follow-up are necessary during treatment.

Breast adenoid cystic carcinoma: a report of seven cases and literature review.

BACKGROUND: Primary adenoid cystic carcinoma (ACC) of breast is rarely seen clinically. It is a special subtype of triple-negative breast cancer characterized by low expression of Ki-67, low malignant potential, slow progression and favorable prognosis. To date, treatment for this disease is controversial and no consensus is reached. We analyzed clinical manifestations and pathological characteristics of seven primary breast ACC cases and reported in combination with literature review to promote understanding, diagnosis and treatment of this disease. CASE PRESENTATION: We collected seven breast ACC cases pathologically diagnosed and treated in Department of breast surgery of the First Affiliated Hospital of China Medical University from January 2015 to December 2018. We organized and summarized the clinical, imaging, pathological and prognostic information and performed statistical analysis. The median age was 60 years (ranging from 54 to 64 years). Tumors of all patients were detected by immunohistochemistry. Molecular types were mostly triple negative (4/7), and Ki-67 expression was low (5/7). Lymph node metastases were absent in all patients received axillary lymph node surgery. Median follow-up time was 39 months (ranging from 25 to 68 months). There was no occurrence of relapse, distant metastasis or death. CONCLUSION: Breast ACC is accompanied with favorable diagnosis, which is different from typical triple-negative breast cancer. Accurate diagnosis of ACC is particularly important.

DEAD-box helicase 27 enhances stem cell-like properties with poor prognosis in breast cancer.

BACKGROUND: Although the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer. METHODS: The expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan-Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer. RESULTS: DDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS, p = 0.0087) and disease-free survival (DFS, p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells. CONCLUSION: DDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.

LncRNA SPRY4-IT1 regulates breast cancer cell stemness through competitively binding miR-6882-3p with TCF7L2.

SPRY4-intronic transcript 1 has been found in several kinds of cancers, but the role of SPRY4-IT1 in breast cancer stem cells has not been studied. We investigated whether SPRY4-IT1 is involved in the promotion of breast cancer stem cells (BCSCs). We used qRT-PCR to detect the expression of SPRY4-IT1 in MCF-7 cells and MCF-7 cancer stem cells (MCF-7 CSCs). The effects of SPRY4-IT1 on the proliferation and renewal ability of breast cancer cells were investigated by in vitro and in vivo assays (ie in situ hybridization, colony formation assay, sphere formation assay, flow cytometry assay, western blotting, xenograft model and immunohistochemistry). The mechanism of SPPRY4-IT1 as a ceRNA was studied by a dual-luciferase reporter assay and bioinformatic analysis. In our study, SPRY4-IT1 was up-regulated in MCF-7 CSCs compared with MCF-7 cells, and high SPRY4-IT1 expression was related to reduced breast cancer patient survival. Furthermore, SPRY4-IT1 overexpression promoted breast cancer cell proliferation and stemness in vitro and in vivo. In addition, SPRY4-IT1 knockdown suppressed BCSC renewal ability and stemness maintenance in vivo and in vitro. The dual-luciferase reporter assays indicated that SPRY4-IT1 as a sponge for miR-6882-3p repressed transcription factor 7-like 2 (TCF7L2) expression. Taken together, these findings demonstrated that SPRY4-IT1 promotes proliferation and stemness of breast cancer cells as well as renewal ability and stemness maintenance of BCSCs by increasing the expression of TCF7L2 through targeting miR-6882-3p.

The bZIP53-IAA4 module inhibits adventitious root development in Populus.

Adventitious roots (ARs) are important for some plants that depend on clonal propagation. In this study, we demonstrate that a salt-responsive gene module is involved in the negative regulation of AR development in poplar. In this module, the expression of bZIP53 is induced by salt stress and it encodes a transcription factor with transactivation activity. Overexpression or induced expression of bZIP53 in poplar lines resulted in inhibition of AR growth, while heterologous overexpression of bZIP53 in Arabidopsis resulted in a similar phenotype. Results from RNA-seq and RT-qPCR assays predicted IAA4-1 and IAA4-2 to be downstream genes that were regulated by bZIP53. Further investigation of protein-DNA interactions using yeast one-hybrid, electrophoretic mobility shift, dual luciferase reporter, and GUS co-expression assays also showed that IAA4-1/2 were the genes that were directly regulated by bZIP53. Induced-expression IAA4-1/2 transgenic poplar lines also showed inhibited AR growth. In addition, both poplar bZIP53 and IAA4-1/2 showed a response to salt stress. On the basis of these results, we conclude that the bZIP53-IAA4 module is involved in the negative regulation of AR development in poplar.

Combining QTL Mapping with Genome Resequencing Identifies an Indel in an R Gene that is Associated with Variation in Leaf Rust Disease Resistance in Poplar.

Poplar trees (Populus spp.) are important and are widely grown worldwide. However, the extensive occurrence of leaf rust disease caused by Melampsora spp. seriously inhibits their growth and reduces their biomass. In our previous study, a high-quality genetic map was constructed for the poplar F1 population I-69 × XYY by using next-generation sequencing-based genotyping-by-sequencing. Here, we collected phenotypic data on leaf rust disease resistance on three different dates for all 300 progenies of the F1 population. Combining a high-quality genetic map and phenotypic data, we were able to detect 11 major quantitative trait loci (QTLs) for leaf rust disease resistance. Among these 11 QTLs, two pairs were detected on at least two dates. In the corresponding genomic sequence, we found that resistance (R) gene clusters were located in these two QTL regions. By using genome resequencing, PCR confirmation and statistical analysis, a 611-bp deletion within an R gene in one QTL region was found to be associated with variation in leaf rust disease resistance. A PCR-based examination of this 611-bp deletion was performed. This 611-bp deletion was also found to affect mRNA splicing and form a new protein with the loss of some key protein domains. Based on this study, we were able to determine the genetic architecture of variation in poplar leaf rust disease resistance, and the 611-bp deletion in the R gene could be used as a diagnostic marker for future poplar molecular breeding.

Brain-Heart Axis and Biomarkers of Cardiac Damage and Dysfunction after Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac complications after a stroke are the second leading cause of death worldwide, affecting the treatment and outcomes of stroke patients. Cardiac biomarkers such as cardiac troponin (cTn), brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been frequently reported in patients undergoing a stroke. The aim of the present study is to meta-analyze the relationship between changes in such cardiac biomarkers and stroke and to present a systematic review of the previous literature, so as to explore the brain-heart axis. METHODS: We searched four online databases pertinent to the literature, including PubMed, Embase, the Cochrane Library, and the Web of Science. Then, we performed a meta-analysis to investigate changes in cTn, BNP, and NT-proBNP associated with different types of stroke. RESULTS AND CONCLUSIONS: A significant increase in cTnI concentration was found in patients exhibiting a brain hemorrhage. BNP increased in cases of brain infarction, while the NT-proBNP concentration was significantly elevated in patients suffering an acute ischemic stroke and brain hemorrhage, indicating cardiac damage and dysfunction after a stroke. Our analysis suggests that several potential mechanisms may be involved in the brain-heart axis. Finally, clinicians should pay careful attention to monitoring cardiac function in the treatment of cerebrovascular diseases in order to provide a timely and more accurate treatment.

Improving Education About Breast Cancer for Medical Students in China.

In traditional medical school curriculum of cancer education in China, there is a very limited amount of teaching about breast cancer. The current situation may result in indifference to breast cancer education among medical students. Case-based learning (CBL) is a popular teaching method based on clinical cases. To date, there are few research reports about the application and research of CBL in breast cancer education. The aim of this study is to explore the teaching effect about CBL combined with lecture-based learning (LBL) in breast cancer education. Questions of breast cancer in National Medical Licensing Examination (NMLE) from 2011 to 2018 were analyzed. The questions about breast cancer were used as the evaluation criteria for this study. In this pilot study, a total of 140 students were randomly divided into a lecture only group (control group) and a lecture plus CBL group (observation group). The students in the observation group had better academic performances and abilities of memory, understanding, and application. They also had higher favorable impressions of the learning experience. In conclusion, more active approaches yield more learning and are viewed more favorably. CBL plus lecture can significantly improve education about breast cancer among medical students, which may be an important message for the evolution of curriculum in Chinese medical schools.

Comprehensive analysis of dynamic gene expression and investigation of the roles of hydrogen peroxide during adventitious rooting in poplar.

BACKGROUND: Adventitious roots (ARs) are roots that are generated from nonrooting tissues. ARs are usually produced both during normal development and in response to stress conditions, such as flooding, nutrient deprivation, heavy metal stress and wounding. The ability of plants to form ARs is a key trait that enables plant propagation, especially for most tree species. RESULTS: Here, the kinetics of AR formation in a tissue culture of a hybrid variety of poplar were investigated. AR formation mainly occurred during the first 8 days and both pre- and newly- formed primordia contributed to AR formation in poplar by histological study. RNA-Seq-based transcriptome analysis was performed for stem bases collected at 0, 2, 4, 6 and 8 days after excision (DAE). Based on the data, the expression patterns of 8 phytohormone-related genes were investigated, and their influences on AR formation were considered. Subsequent gene expression cluster analysis showed a number of biological processes involved in AR formation. Among these biological pathways, genes involved in H2O2 homeostasis showed enrichment in one cluster that was highly upregulated from DAE0 to DAE8. Pharmacological assay confirmed that an appropriate content of H2O2 in stem bases could accelerate the formation of ARs in poplar. CONCLUSIONS: Based on the results of this study, we were able to predict a regulatory network for 7 phytohormones that are involved in poplar AR formation. The influence of H2O2 on AR formation was also confirmed. These results enhance our understanding of the regulation of AR formation in tree species.

Clinical implications of a novel prognostic factor AIFM3 in breast cancer patients.

BACKGROUND: In a time of increasing concerns over personalized and precision treatment in breast cancer (BC), filtering prognostic factors attracts more attention. Apoptosis-Inducing Factor Mitochondrion-associated 3 (AIFM3) is widely expressed in various tissues and aberrantly expressed in several cancers. However, clinical implication of AIFM3 has not been reported in BC. The aim of the study is to investigate the crystal structure, clinical and prognostic implications of AIFM3 in BC. METHODS: AIFM3 expression in 151 BC samples were assessed by immunohistochemistry (IHC). The Cancer Genome Atlas (TCGA) and Kaplan-Meier survival analysis were used to demonstrate expression and survival of AIFM3 signature. Gene Set Enrichment Analysis (GSEA) was performed to investigate the mechanisms related to AIFM3 expression in BC. RESULTS: AIFM3 was significantly more expressed in breast cancer tissues than in normal tissues. AIFM3 expression had a significant association with tumor size, lymph node metastasis, TNM stage and molecular typing. Higher AIFM3 expression was related to a shorter overall survival (OS) and disease-free survival (DFS). Lymph node metastasis and TNM stage were independent factors of AIFM3 expression. The study presented the crystal structure of AIFM3 successfully and predicted several binding sites when AIFM3 bonded to PTPN12 by Molecular Operating Environment software (MOE). CONCLUSIONS: AIFM3 might be a potential biomarker for predicting prognosis in BC, adding to growing evidence that AIFM3 might interact with PTPN12.

Construction of a high-density genetic map and its application for leaf shape QTL mapping in poplar.

MAIN CONCLUSION: High-quality and dense genetic maps were constructed, and leaf shape variation was dissected by QTL mapping in poplar. Species in the genus Populus, also known as poplars, are important woody species and considered model plants for perennial trees. High-density genetic maps are valuable genomic resources for population genetics. Here, we generated a high-quality and dense genetic map for an F1 poplar population using high-throughput NGS-based genotyping. A total of 92,097 high-quality SNP markers were developed by stringent filtering and identification. In total, 889 and 1650 SNPs formed the female and male genetic maps, respectively. To test the application of the genetic maps, QTL mapping of leaf shape was conducted for this F1 population. A total of nine parameters were scored for leaf shape variation in three different environments. Combining genetic maps and measurements of the nine leaf shape parameters, we mapped a total of 42 significant QTLs. The highest LOD score of all QTLs was 9.2, and that QTL explained the most (15.13%) trait variation. A total of nine QTLs could be detected in at least two environments, and they were located in two genomic regions. Within these two QTL regions, some candidate genes for regulating leaf shape were predicted through functional annotation. The successful mapping of leaf shape QTLs demonstrated the utility of our genetic maps. According to the performance of this study, we were able to provide high-quality and dense genetic maps and dissect the leaf shape variation in poplar.

How great is the medical burden of disease on the aged? Research based on "System of Health Account 2011".

BACKGROUND: The aging of population and the burden of disease among the aged have become one of the hot topics in the international health, and also brought tremendous pressure in the development of health service. METHODS: A total of 1,377,681 patients aged 65 years and over were collected with multistage stratified cluster random sampling in 252 medical institutions in Liaoning China, and "System of Health Account 2011" was conducted to analyze the expenditure of disease for the elderly. Influencing factors were performed using multiple stepwise regression analysis. RESULTS: The curative care expenditure for the aged was 233.18 billion RMB. Most of the expenditure for the old people was in hospital. Moreover, by the disease, the highest expenditure was incurred by non-communicable diseases. The financing scheme of the aged was concentrated on social health insurance and family health expenditure. Hospitalization expenditure was significantly associated with length of stay, operation, etc. CONCLUSIONS: This study intends to capture large data from various medical institutions with a new accounting system. The finding illustrates that the burden of old people is still heavy.

Integration of rural and urban healthcare insurance schemes in China: an empirical research.

BACKGROUND: Despite the broad coverage of the healthcare insurance system in China, the imbalances in fairness, accessibility and affordability of healthcare services have hindered the universal healthcare progress. To provide better financial protection for the Chinese population, China's new medical reform was proposed to link up urban employee basic medical insurance scheme (UEBMI), urban resident basic medical insurance scheme (URBMI), new rural cooperative medical system (NRCMS) and urban and rural medical assistance programs. In this paper, we focused on people's expected healthcare insurance model and their willingness towards healthcare insurance integration, and we made a couple of relative policy suggestions. METHODS: A questionnaire survey was conducted in four cities in China. A total of 1178 effective questionnaires were retrieved. Statistical analysis was conducted with SPSS and Excel. Chi-square test and logistic regression model were applied. RESULTS AND DISCUSSION: The payment intention and reimbursement expectation of the three groups varied with NRCMS participants the lowest and UEBMI participants the highest. In economic developed areas, rural residents had equal or even stronger payment ability than urban residents, and the overall payment intention showed a scattered trend; while in less developed areas, urban residents had a stronger payment ability than rural residents and a more concentrated payment intention was observed. The majority of participants favored the integration, with NRCMS enrollees up to 80.5%. In the logistic regression model, we found that participants from less developed areas were more likely to oppose the integration, which we conceived was mainly due to their dissatisfaction with their local healthcare insurance schemes. Also the participants with better education background tended to oppose the integration, which might be due to their fear of benefit impairment and their concern about the challenges ahead. CONCLUSION: Even though there are many challenges for healthcare insurance integration, it has received strong support from the mass population. However, more emphasis shall be put on equal financing and equal benefit when making further policies. As the current healthcare policies share the same design concept, principle and method, the ultimate goal of establishing a universal healthcare system is promising.

The effects of China's New Cooperative Medical Scheme on accessibility and affordability of healthcare services: an empirical research in Liaoning Province.

BACKGROUND: China's New Cooperative Medical Scheme (NCMS), launched in 2003, was intended to prevent the impoverishment due to catastrophic illness costs. Previous studies have been conducted on the "design flows" of the NCMS, for example, the irrational insurance benefit package. But after several years of implementation, very little has been known about the improvements made by the NCMS and rural residents' attitudes toward it. This article specifically focused on the improvements of healthcare services and the enrollees' choices of providers since the implementation of the NCMS in Liaoning province. METHODS: We conducted a one-on-one interview with healthcare officials in order to get a better understanding of the NCMS policies of the local area. We conducted a door-to-door survey in 3 counties, 21 villages and 602 households to gauge population characteristics, respondents' healthcare preferences, satisfaction levels with providers, and their attitudes towards designated healthcare institutions. RESULTS: We found that 43.6% of the respondents believed the NCMS brought more convenience to receive healthcare services. 35.2% of the rural residents thought the NCMS work ineffectively, mainly due to the high healthcare costs. 72.3% of the respondents preferred the county hospitals when they got severe diseases, mainly for the reason of better skills and more advanced equipment, while they preferred village clinics (56.5%) and township hospitals (23.2%) when they got minor diseases mainly for the reason of convenience. CONCLUSION: We concluded that the NCMS improved the situation of hard to receive healthcare services but did not reduce the high healthcare fees. Furthermore, participants were unsatisfied with the NCMS designated hospitals. Based on our findings, a number of remedial actions were proposed, including redistributing healthcare resources, developing more domestic medical equipment to lower the treatment costs, and establishing a new talent flow mode.

Adaptive neural identification and non-singular control of pure-feedback nonlinear systems.

This paper proposes a new constructive identification and adaptive control method for nonlinear pure-feedback systems, which remedies the 'explosion of complexity' and potential control singularity encountered in the traditional adaptive backstepping controllers. First, to avoid using the backstepping recursive design, alternative state variables and the corresponding coordinate transformation are introduced to reformulate the pure-feedback system into an equivalent canonical model. Then, a high-order sliding mode (HOSM) observer is used to reconstruct the unknown states for this canonical model. To remedy the potential singularity in the control, the unknown system dynamics are lumped to derive an alternative identification structure and one-step control synthesis, where two radial basis function neural networks (RBFNN) are adopted to online estimate these lumped dynamics. In this framework, the online estimation of control gain is not in the denominator of controller, and thus the division by zero in the controllers is avoided. Finally, a new online learning algorithm is constructed to obtain the RBFNNs' weights, ensuring the convergence to the neighborhood of true values and allowing accurate identification of unknown dynamics. Theoretical analysis elaborates that the convergence of both the tracking error and the estimation error is obtained simultaneously. Simulations and practical experiments on a hydraulic servo test-rig verify the effectiveness and utility of the suggested methods.

SNORA5A regulates tumor-associated macrophage M1/M2 phenotypes via TRAF3IP3 in breast cancer.

Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.

Macrophages and tertiary lymphoid structures as indicators of prognosis and therapeutic response in cancer patients.

Tertiary lymphoid structures (TLS) can reflect cancer prognosis and clinical outcomes in various tumour tissues. Tumour-associated macrophages (TAMs) are indispensable components of the tumour microenvironment and play crucial roles in tumour development and immunotherapy. TAMs are associated with TLS induction via the modulation of the T cell response, which is a major component of the TLS. Despite their important roles in cancer immunology, the subtypes of TAMs that influence TLS and their correlation with prognosis are not completely understood. Here, we provide novel insights into the role of TAMs in regulating TLS formation. Furthermore, we discuss the prognostic value of these TAM subtypes and TLS, as well as the current antitumour therapies for inducing TLS. This study highlights an entirely new field of TLS regulation that may lead to the development of an innovative perspective on immunotherapy for cancer treatment.