Prognostic value of lncRNA AFAP1-AS1 in breast cancer: a meta-analysis and validated study in Chinese population.

BACKGROUND: Long non encoding RNA (lncRNA) plays a crucial role in breast cancer. However, the prognostic role of AFAP1-AS1 in breast cancer remains unclear. AIMS: To investigate the relationship between the expression of long non-coding RNA actin filament-associated protein1 antisense RNA1 (AFAP1-AS1) and prognosis of breast cancer. METHODS AND RESULTS: Meta-analysis was performed to explore the correlation between AFAP1-AS1 and breast cancer. The AFAP1-AS1expression in patients with breast cancer tissue and adjacent normal tissue from 153 patients was determined by qRT-PCR. Bioinformatics and Cox proportional-hazards risk model were used to explore the relationship between expression of AFAP1-AS1 and prognosis. The combined analysis revealed a significant correlation between AFAP1-AS1 expression and both overall survival (hazard ratios, HR = 2.33, 95%Cl: 1.94-2.81, p < 0.001) as well as disease-free survival/progression-free survival (HR = 2.94, 95%CI: 2.35-3.67, p < 0.001). The relation between expression of AFAP1-AS1 and breast cancer was determined in 153 breast cancer and adjacent normal tissues. The findings revealed a significantly higher AFAP1-AS1expression levels in breast cancer tissues compared to adjacent normal tissues (p < 0.001). Additionally, patients exhibiting heightened levels of AFAP1-AS1 expression were correlated with an unfavorable prognosis (HR = 2.35, 95%CI: 1.47-3.74, p < 0.001), which aligns consistently with the findings of the pooled analysis. The subgroup analysis of clinical characteristics revealed a significant association between high expression of AFAP1-AS1 and TNM stage (HR = 1.72, 95%CI: 1.11-2.65, p = 0.015). CONCLUSION: This study demonstrated that AFAP1-AS1 acts as an oncogene and may serve as a novel prognostic marker for breast cancer, particularly in the Chinese population.

Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial.

CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as front-line treatment in women with HER2-positive advanced BC (n = 41) including those with HR-negative disease. The primary endpoint is the objective response rate, and secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of assessable patients have a confirmed objective response, meeting the primary endpoint. The median PFS is 11.0 months (95% CI = 7.3-19.3), and OS data are not mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. These findings suggest that this combination may have promising activity and manageable toxicity. Further investigation is needed.

Recent insights into autophagy and metals/nanoparticles exposure.

Some anthropogenic pollutants, such as heavy metals and nanoparticles (NPs), are widely distributed and a major threat to environmental safety and public health. In particular, lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), and mercury (Hg) have systemic toxicity even at extremely low concentrations, so they are listed as priority metals in relation to their significant public health burden. Aluminum (Al) is also toxic to multiple organs and is linked to Alzheimer's disease. As the utilization of many metal nanoparticles (MNPs) gradually gain traction in industrial and medical applications, they are increasingly being investigated to address potential toxicity by impairing certain biological barriers. The dominant toxic mechanism of these metals and MNPs is the induction of oxidative stress, which subsequently triggers lipid peroxidation, protein modification, and DNA damage. Notably, a growing body of research has revealed the linkage between dysregulated autophagy and some diseases, including neurodegenerative diseases and cancers. Among them, some metals or metal mixtures can act as environmental stimuli and disturb basal autophagic activity, which has an underlying adverse health effect. Some studies also revealed that specific autophagy inhibitors or activators could modify the abnormal autophagic flux attributed to continuous exposure to metals. In this review, we have gathered recent data about the contribution of the autophagy/mitophagy mediated toxic effects and focused on the involvement of some key regulatory factors of autophagic signaling during exposure to selected metals, metal mixtures, as well as MNPs in the real world. Besides this, we summarized the potential significance of interactions between autophagy and excessive reactive oxygen species (ROS)-mediated oxidative damage in the regulation of cell survival response to metals/NPs. A critical view is given on the application of autophagy activators/inhibitors to modulate the systematic toxicity of various metals/MNPs.

Increased lncRNA AFAP1-AS1 expression predicts poor prognosis in gastric cancer: Evidence from published studies and followed up verification.

AIM: The purpose of this study was to clarify the influence of long non-coding RNA actin fiber-associated protein-1 antisense RNA 1 (lncRNA AFAP1-AS1) on the prognosis of gastric cancer (GC). METHODS: Based on meta-analysis, the association between the expression of AFAP1-AS1 and the prognosis of GC was estimated. GC tissue and non-cancer tissues from 136 patients were determined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and verified by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier and Cox proportional hazards models were conducted to analyze the correlation between AFAP1-AS1 expression and GC prognosis. RESULTS: The pooled analysis from five studies revealed that the AFAP1-AS1 expression was significantly associated with GC overall survival (hazard ratio (HR) = 2.49 and 95% confidence interval (95% CI): 2.02-3.08, p < 0.001). Compared with non-cancer tissues, AFAP1-AS1 expression level of GC tissues were significantly upregulated (p < 0.001), which was confirmed by the results of GEPIA. The area under the receiver-operating characteristic (ROC) curve was 0.893, and the high expression of AFAP1-AS1 was correlated with poor prognosis in patients with GC (p = 0.005). Clinical grade (HR = 1.912, 95% CI: 1.246-2.934, p = 0.003), pathologic tumor node metastasis (pTNM) (HR = 2.393, 95% CI: 1.431-4.033, p = 0.001), log odds of positive lymph nodes (LODDS) (HR = 2.910, 95% CI: 1.787-4.793, p < 0.001) and AFAP1-AS1 expression (HR = 2.393, 95% CI: 1.869-3.064, p < 0.001) were independent prognostic factors for GC revealed by multivariate Cox-regression analysis. CONCLUSION: This study demonstrated that the AFAP1-AS1 may be a novel biomarker for the diagnosis and prognosis of GC.

Hydrogen gas alleviates lipopolysaccharide-induced acute lung injury and inflammatory response in mice.

BACKGROUND: Chronic inflammation and oxidant/antioxidant imbalance are two main pathological features associated with lipopolysaccharide (LPS)-induced acute lung injury (ALI). The following study investigated the protective role of hydrogen (H2), a gaseous molecule without known toxicity, in LPS-induced lung injury in mice and explored its potential molecular mechanisms. METHODS: Mice were randomly divided into three groups: H2 control group, LPS group, and LPS + H2 group. The mice were euthanized at the indicated time points, and the specimens were collected. The 72 h survival rates, cytokines contents, pathological changes, expression of Toll-like receptor 4 (TLR4), and oxidative stress indicators were analyzed. Moreover, under different culture conditions, RAW 264.7 mouse macrophages were used to investigate the potential molecular mechanisms of H2 in vitro. Cells were divided into the following groups: PBS group, LPS group, and LPS + H2 group. The cell viability, intracellular ROS, cytokines, and expression of TLR4 and nuclear factor kappa-B (NF-κB) were observed. RESULTS: Hydrogen inhalation increased the survival rate to 80%, reduced LPS-induced lung damage, and decreased inflammatory cytokine release in LPS mice. Besides, H2 showed remarked anti-oxidative activity to reduce the MDA and NO contents in the lung. In vitro data further indicated that H2 down-regulates the levels of ROS, NO, TNF-α, IL-6, and IL-1ß in LPS-stimulated macrophages and inhibits the expression of TLR4 and the activation of nuclear factor kappa-B (NF-κB). CONCLUSION: Hydrogen gas alleviates lipopolysaccharide-induced acute lung injury and inflammatory response most probably through the TLR4-NF-κB pathway.

Identification of Inosine and 2'-O-Methylinosine Modifications in Yeast Messenger RNA by Liquid Chromatography-Tandem Mass Spectrometry Analysis.

The discovery of reversible modifications in messenger RNA (mRNA) opens new research directions in RNA modification-mediated epigenetic regulation. Yeast is an extensively used model organism in molecular biology. Systematic investigation and profiling of modifications in yeast mRNA would promote our understanding of the physiological regulation mechanisms in yeast. However, due to the high abundance of ribosomal RNA (rRNA) and transfer RNA (tRNA) in total RNA, isolation of low abundance of mRNA frequently suffers from the contamination of rRNA and tRNA, which will lead to the false-positive determination and inaccurate quantification of modifications in mRNA. Therefore, obtaining high-purity mRNA is critical for precise determination and accurate quantification of modifications in mRNA, especially for studies that focus on discovering new ones. Herein, we proposed a successive orthogonal isolation method by combining polyT-based purification and agarose gel electrophoresis purification for extracting high-purity mRNA. With the extracted high-purity yeast mRNA, we systemically explored the modifications in yeast mRNA by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. The results showed that in addition to the previously reported eight kinds of modifications, two novel modifications of inosine (Ino) and 2'-O-methylinosine (Im) were identified to be prevalent in yeast mRNA. It is worth noting that Im was reported for the first time, to the best of our knowledge, to exist in living organisms in the three domains of life. Moreover, we observed that the levels of 10 kinds of modifications including Ino and Im in yeast mRNA exhibited dynamic change at different growth stages of yeast cells. Furthermore, Im in mRNA showed a significant decrease while in response to H2O2 treatment. These results indicated that the two newly identified modifications in yeast mRNA were involved in yeast cell growth and response to environmental stress. Taken together, we reported two new modifications of Ino and Im in yeast mRNA, which expends the diversity of RNA modifications in yeast and also suggests new regulators for modulating yeast physiological functions.

Phenotype and management of chronic obstructive pulmonary disease patients in general population in China: a nationally cross-sectional study.

This study aims to investigate the characteristics of the phenotype and management of chronic obstructive pulmonary disease (COPD) patients in the general population in China. We analyzed spirometry-confirmed COPD patients who were identified from a population-based, nationally representative sample in China. All participants were measured with airflow limitation severity based on post-bronchodilator FEV1 percent predicted, bronchodilator responsiveness, exacerbation history, and respiratory symptoms. Among a total of 9134 COPD patients, 90.3% were non-exacerbators, 2.9% were frequent exacerbators without chronic bronchitis, 2.0% were frequent exacerbators with chronic bronchitis, and 4.8% were asthma-COPD overlap. Less than 5% of non-exacerbators ever had pulmonary function testing performed. The utilization rate of inhaled medication in non-exacerbators, exacerbators without chronic bronchitis, exacerbators with chronic bronchitis, and asthma-COPD overlap was 1.4, 23.5, 29.5, and 19.4%, respectively. A comprehensive strategy for the management of COPD patients based on phenotype in primary care is urgently needed.

PM2.5 exposure induces reproductive injury through IRE1/JNK/autophagy signaling in male rats.

Fine particulate matter (PM2.5) constitutes the most significant air pollutant that causes health risks. However, the mechanism(s) underlying PM2.5-induced male reproductive injury has not been clarified. In the present study we explored whether PM2.5 activated the inositol-requiring enzyme 1 (IRE1)/c-Jun NH 2-terminal kinase (JNK)/autophagy-signaling pathway, and whether this pathway mediated reproductive injury in male rats. We established a male Sprague-Dawley rat model of PM2.5 (1.5 mg/kg) exposure-induced reproductive injury, and observed the intervention effects of STF083010 (an IRE1 inhibitor, 1 mg/kg). After 4 weeks of exposure, reproductive injury-related indicators and IRE1-cascade protein expression were analyzed. Our results showed that sperm quality and serum testosterone level significantly decreased and apoptotic index increased after exposure to PM2.5. After STF083010 intervention, sperm quality and serum testosterone level were significantly improved, while the apoptotic index was reduced. Under light microscopy, we observed that the structure of spermatogenic cells in the PM2.5 group was loose, and that the numbers of spermatogenic cells and mature spermatozoa were reduced. After STF083010 intervention, the structural damage to spermatogenic cells was improved, and the number of cells shed was reduced. Western blotting analysis showed that the expression of IRE1, phosphorylated JNK (p-JNK), beclin-1, and microtubule-associated protein 1 light chain 3(LC3)II/LC3I proteins was significantly upregulated, and that the expression of p62 protein was significantly downregulated in the PM2.5 group. The concomitant administration of STF083010 significantly antagonized the aforementioned adverse effects. STF083010 exerted specific protective effects on reproductive injury-related effects in male rats exposed to PM2.5, with effects mediated via IRE1/JNK/autophagy signaling.

Investigating the safety and compliance of using csDMARDs in rheumatoid arthritis treatment through face-to-face interviews: a cross-sectional study in China.

Rheumatoid arthritis (RA) significantly impacts the health of Chinese patients. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used as the standard treatment for patients with RA. However, Chinese patients with RA have reported poor compliance with csDMARDs. This study aims to better understand the safety and compliance of using csDMARDs in RA treatment. Face-to-face interviews were conducted by questionnaires on safety and compliance of csDMARDs in 400 patients with RA and 100 rheumatologists from 13 cities in China. Rheumatologists were from Tier 3 Class A hospitals with independent rheumatology departments, who admitted more than 30 patients with RA per week. All patients were diagnosed for > 3 months before the survey and had been treated with csDMARDs for > 3 months. The incidence of adverse events (AEs) that attributed to csDMARDs estimated by rheumatologists was lower than that reported by patients for all four prescribed csDMARDs. Also, types of common AEs in rheumatologist's perception differed from those in the patient's report. Only 86% (116/135) of patients claimed they notified their rheumatologist about AEs, and 40.8% (150/368) of patients did not strictly adhere to their prescribed treatment. Reasons why patients were not compliant with their treatment, other than AEs, included symptoms being less severe, travel, and busy working life/business trips. This study revealed gaps in perceptions of csDMARDs-related AEs and medication adherence between rheumatologists and patients. These findings suggested adequate doctor-patient communications, and considerations of multiple real-world situations may improve adherence in the treatment of RA patients. Key Points • This study identified gaps in rheumatologists' perception of the prevalence and type of AEs experienced by their patients, which could potentially help them improve their patients' compliance with treatment.

Geographical Disparity and Associated Factors of COPD Prevalence in China: A Spatial Analysis of National Cross-Sectional Study.

Purpose: COPD prevalence has rapidly increased in China, but the geographical disparities in COPD prevalence remain largely unknown. This study aimed to assess city-level disparities in COPD prevalence and identify the relative importance of COPD related risk factors in mainland China. Patients and Methods: A nationwide cross-sectional study of COPD recruited 66,752 adults across the mainland China between 2014 and 2015. Patients with COPD were ascertained by a post-bronchodilator pulmonary function test. We estimated the city-specific prevalence of COPD by spatial kriging interpolation method. We detected spatial clusters with a significantly higher prevalence of COPD by spatial scan statistics. We determined the relative importance of COPD associated risk factors by a nonparametric and nonlinear classification and regression tree (CART) model. Results: The three spatial clusters with the highest prevalence of COPD were located in parts of Sichuan, Gansu, and Shaanxi, etc. (relative risks (RRs)) ranging from 1.55 (95% CI 1.55-1.56) to 1.33 (95% CI 1.33-1.33)). CART showed that advanced age (≥60 years) was the most important factor associated with COPD in the overall population, followed by smoking. We estimated that there were about 28.5 million potentially avoidable cases of COPD among people aged 40 or older if they never smoked. PM2.5 was an important associated risk factor for COPD in the north, northeast, and southwest of China. After adjusting for age and smoking, the spatial cluster with the highest prevalence shifted to most of Sichuan, Gansu, Qinghai, and Ningxia, etc. (RR 1.65 (95% CI 1.63-1.67)). Conclusion: The spatial clusters of COPD at the city level and regionally varied important risk factors for COPD would help develop tailored interventions for COPD in China. After adjusting for the main risk factors, the spatial clusters of COPD shifted, indicating that there would be other potential risk factors for the remaining clusters which call for further studies.

Influenza vaccination rate and its association with chronic diseases in China: Results of a national cross-sectional study.

INTRODUCTION: Influenza vaccination is the most effective way to prevent influenza. Few studies on its rate were reported throughout China and for populations with chronic diseases. An estimation of the rates in China was accomplished. METHODS: All data were from a national cross-sectional survey of a sample representing the population aged 40 years or older in mainland China in 2014-15. A total of 74,484 individuals with complete self-reported influenza vaccination status were analyzed in 2018-19. RESULTS: The overall influenza vaccination rate was 2.4% (95% CI 1.4-3.3) with 1.7% (95% CI 1.2-2.2) for the age group 40-59 years and 3.8% (95% CI 1.6-5.9) for the group ≥60 years. The rate was 4.0% (95% CI 2.0-5.9) among people with a chronic disease. People with asthma and people with emphysema had the highest rates (7.1%, 95% CI 3.2-11.0 and 6.6%, 95% CI 3.6-9.7) while people with chronic obstructive pulmonary disease (COPD) and people with chronic bronchitis had the lower rates (3.6%, 95% CI 2.0-5.2 and 4.8%, 95% CI 2.6-7.0). The rate was the highest among former smokers (3.3%, 95% CI 2.3-4.4) compared to current smokers (1.8%, 95% CI 0.9-2.7) and never smokers (2.5%, 95% CI 1.4-3.6). People living with finance-reimbursed vaccination policy, a positive factor for vaccination, had a higher vaccination rate (11.5%, 95% CI 10.8-12.2) (p < 0.05). People with older age, higher education level, occupation of professionals or technical personnel, living in rural areas or Northern China, former/never smoking were more likely to be vaccinated (p < 0.05). CONCLUSIONS: The influenza vaccination rate is low among adults aged ≥40 years, those ≥60 years and those with chronic diseases in China. Reimbursement policy targeting the elderly should be implemented widely and strategies towards patients with chronic diseases need urgent attention to increase the influenza vaccination coverage.

Prognostic values of microRNA-130 family expression in patients with cancer: a meta-analysis and database test.

BACKGROUND: Emerging evidence shows that microRNA-130 (miRNA-130) family may be useful as prognostic biomarkers in cancer. However, there is no confirmation in an independent validation study. The aim of this study was to summarize the prognostic value of miRNA-130 family (miRNA-130a and miRNA-130b) for survival in patients with cancer. METHODS: The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the association strength between miRNA-130 family expression and prognosis. Kaplan-Meier plotters were used to verify the miRNA-130b expression and overall survival (OS). RESULTS: A total of 2141 patients with OS and 1159 patients with disease-free survival (DFS)/progression-free survival (PFS) were analyzed in evidence synthesis. For the miRNA-130a, the overall pooled effect size (HR) was HR 1.58 (95% CI: 1.21-2.06, P < 0.001). Tissue and serum expression of miRNA-130a was significantly associated with the OS (HR = 1.54, 95% CI: 1.11-2.14, P = 0.009; HR = 1.65, 95% CI: 1.14-2.38, P = 0.008), and in gastric cancer (HR = 1.81, 95% CI: 1.34-2.45, P < 0.001). For the miRNA-13b, a statistical correlation was observed between high miRNA-130b expression and poor OS in patients with cancer (HR = 1.95, 95% CI: 1.47-2.59, P < 0.001), especially in tissue sample (HR = 2.01, 95% CI: 1.39-2.91, P < 0.001), Asian (HR = 2.55, 95% Cl: 1.77-3.69, P < 0.001) and hepatocellular carcinoma (HR = 1.87, 95% CI: 1.23-2.85, P = 0.004). The expression of miRNA-130b was significantly correlated with DFS/PFS (HR = 1.53, 95% CI: 1.31-1.77, P < 0.001), in tissue (HR = 1.98, 95% CI: 1.50-2.62, P < 0.001) and serum (HR = 1.37, 95% CI: 1.15-1.64, P < 0.001), especially in HCC (HR = 1.98, 95% CI: 1.50, 2.62, P < 0.001). In database test, a significant correlation between high miRNA-130b expression and poor OS for HCC patients was observed (HR = 1.55, 95% CI: 1.01, 2.35, P = 0.0045). CONCLUSION: The high expression of miRNA-130 family might predict poor prognosis in cancer patients. Prospectively, combining miRNA-130a and miRNA-130b may be considered as powerful prognostic predictor for clinical application.

Evaluation of the epidemiological and prognosis significance of ESR2 rs3020450 polymorphism in ovarian cancer.

AIM: To investigate the correlation between the polymorphism of estrogen receptor ß gene (ESR2) rs3020450 and cancer susceptibility, and explore the epidemiological significance and the effect of ESR2 expression levels on the prognosis of ovarian cancer. METHODS: Based on meta-analysis the association between ESR2 rs3020450 polymorphism and cancer susceptibility was estimated and a case-control design was used to verify this result in ovarian cancer. The epidemiological effect of ESR2 rs3020450 polymorphism was assessed by attributable risk percentage (ARP) and population attributable risk percentage (PARP). Kaplan Meier plotters were used to evaluate overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients and GEPIA for the differential expression of ESR2 levels in ovarian cancer and adjacent normal tissues. RESULTS: The pooled analysis indicated no significant correlation between the ESR2 rs3020450 polymorphism and the cancer susceptibility. In the stratified analysis by cancer types, significantly decreased risk was found in ovarian cancer (AG vs GG: OR = 0.73, 95%CI: 0.53-0.97, P = 0.03). Unconditional logistic regression results of case-control study in ovarian cancer observed significant differences in all comparisons (AG vs GG: OR = 0.81, 95%CI: 0.62-0.98, P = 0.04; AA vs GG: OR = 0.63, 95%CI: 0.42-0.92, P = 0.01 and AG + AA vs GG: OR = 0.73, 95%CI: 0.53-0.96, P < 0.001). Based on meta-analysis and case-control pooled results, ARP and PARP were evaluated respectively in allele (21.95% and7.97%), heterozygote (36.99% and 12.11%) and dominant model (36.84% and 12.97%) of rs3020450 polymorphism in ovarian cancer. The expression levels of ESR2 in normal tissues was significantly higher than that in cancer tissues (OV, Median, 4.7:0.21), and significant correlations were observed between high ESR2 expression levels and long OS (HR = 0.80, 95%CI: 0.70-0.92, P = 0.002) and PFS (HR = 0.767, 95%Cl: 0.67-0.88, P < 0.001). CONCLUSION: Our results indicated that ESR2 rs3020450 polymorphism was associated with ovarian cancer risk from epidemiological perspective, and high ESR2 expression levels was associated with long survival in patients with ovarian cancer.

Personal ultraviolet Radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children study.

BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

Comprehensive Assessment of the Relationship Between MicroRNA-124 and the Prognostic Significance of Cancer.

BACKGROUND: Numerous studies have demonstrated the presence of microRNA-124 abnormalities involving gene expression, methylation, and single nucleotide polymorphism (SNP) in multiple and diverse cancers, but the prognostic value of these abnormalities in cancer remains inconclusive. OBJECTIVE: The aim of this study is to determine the prognostic value of miR-124 in cancer. METHODS: We scrutinized the electronic databases and estimate the association between miR-124 expression, methylation and single nucleotide polymorphisms (SNPs), and prognosis in cancers. The pooled hazard ratios with 95% confidence intervals (CIs) for overall survival (OS), and disease-free survival/recurrence-free survival (RFS)/progression-free survival (PFS) were calculated to estimate the effects of miR-124 expression, methylation, and SNPs on cancer prognosis. The Quality in Prognosis Studies and Newcastle-Ottawa Scale were utilized to assess the quality of included studies. RESULTS: A total of 20 studies involving 3,574 participants were analyzed in evidence synthesis. Our findings showed that the low expression of miR-124 was significantly associated with poor OS (HR = 2.37, 95% CI: 1.91-2.94, P = 0.00; HR = 3.10, 95% CI: 2.04-4.70, P = 0.00) and PFS/RFS (HR = 2.21, 95% CI: 1.50-3.26, P = 0.00; HR = 2.12, 95% CI: 1.20-3.74, P = 0.00). The hyper-methylation of miR-124 was associated with poor OS (HR = 2.09, 95% CI: 1.48-2.95, P = 0.00) and PFS (HR = 3.70, 95% CI: 1.72-7.97, P = 0.00) (Table 3). The patients carrying with Allele C of miR-124 rs5315649 had a worse OS (HR = 1.50, 95% CI: 1.09-2.07, P = 0.00) and PFS (HR = 1.67, 95% CI: 1.20-2.33, P = 0.00) than the carriers with Allele G. CONCLUSION: The low expression and hyper-methylation of miR-124 was strongly associated with poor prognosis, and genetic variations of miR-124 rs531564 affected prognosis in cancer patients.

The Chinese Children and Families Cohort Study: The Nutrition, Physical Activity, and Ultraviolet Radiation Data Collection.

This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

Chronic obstructive pulmonary disease in China: a nationwide prevalence study.

BACKGROUND: Because of the rapid change in economic development and lifestyle in China, and the ageing population, concerns have grown that chronic obstructive pulmonary disease (COPD) could become epidemic. An up-to-date nationwide estimation of COPD prevalence in China is needed. METHODS: We did a cross-sectional survey of a nationally representative sample of individuals from mainland China aged 40 years or older. The primary outcome was COPD, defined according to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) lung function criteria. FINDINGS: Between Dec 29, 2014, and Dec 31, 2015, 66 752 adults were recruited to the study population. The estimated standardised prevalence of COPD was 13·6% (95% CI 12·0-15·2). The prevalence of COPD differed significantly between men and women (19·0%, 95% CI 16·9-21·2 vs 8·1%, 6·8-9·3; p<0·0001), mainly because of a significant difference in smoking status between men and women (current smokers 58·2% vs 4·0%). The prevalence of COPD differed by geographic region, with the highest prevalence in southwest China (20·2%, 95% CI 14·7-25·8) and the lowest in central China (10·2%, 8·2-12·2). Among adults with COPD, 56·4% (95% CI 53·7-59·2) had mild disease (GOLD stage I), 36·3% (34·3-38·3) had moderate disease (GOLD stage II), 6·5% (5·5-7·4) had severe disease (GOLD stage III), and 0·9% (0·6-1·1) had very severe disease (GOLD stage IV). INTERPRETATION: In a large, nationally representative sample of adults aged 40 years or older, the estimated overall prevalence of COPD in China in 2014-15 was 13·6%, indicating that this disease has become a major public-health problem. Strategies aimed at prevention and treatment of COPD are needed urgently. FUNDING: Chinese Central Government, the Ministry of Science and Technology of The People's Republic of China, and the National Natural Science Foundation of China.

The role of ß2 integrin associated heparin-binding protein release in ARDS.

AIMS: PMNs (polymorphonuclear neutrophil) play important roles in early stage of inflammation induced ARDS (Acute Respiratory Distress Syndrome). Both HBP (Heparin-Binding Protein) released from active PMNs and ß2 integrins on the surface of PMNs are involved in vascular leakage. The role and relationship of HBP and ß2 integrins on ARDS still requires study. MATERIALS AND METHODS: We established ARDS model using C57BL/6 mice with cecal ligation and puncture and eliminating HBP and ß2 integrin with respective antibodies. The mice were also challenged with HBP endotracheal instillation. Histopathology score, lung wet/dry ratio, bronchoalveolar lavage fluid protein, plasma HBP and ß2 integrin on PMNs from all groups were measured. ß2 integrin and HBP were analyzed after incubated PMNs with streptococcal and pretreat with anti-CD18, anti-HBP, 1-phosphatidylinositol 3-kinase (PI3K) inhibitor and p38 mitogen-activated protein kinase (MAPK) inhibitor. KEY FINDINGS: All lung injury indicatrix accompanied with HBP and ß2 integrin elevated in CLP group, and HBP and ß2 integrin were in correlation with each other and both were in correlation with the severity of lung injury. Endotracheal instillation HBP induced lung injury in CLP mice. Inhibiting both HBP and integrin ameliorated lung injury. HBP release was suppressed by inhibiting integrin and PI3K pathway, while integrin level did not decrease after eliminating HBP. SIGNIFICANCE: Both HBP and ß2 integrin play important roles in ARDS. HBP released from PMNs is ß2 integrin-PI3K signaling pathway dependent process revealing potential novel therapeutic targets for ARDS treatment.

Neolignan and phenylpropanoid compounds from the fruits of Illicium simonsii Maxim.

One new sesqui-neolignan compound, namely, sesqui-illisimonan A (1), one new neolignan, illisimonan A (2), and one new phenylpropanoid compound, illisimoid A (3) were isolated from the fruits of Illicium simonsii Maxim. The structures and absolute configurations of these compounds were determined by extensive spectroscopic, including NMR, circular dichroism and calculated electronic circular dichroism methods. The antioxidant activities of compounds 1-3 were also evaluated. Vitamin E was selected as the positive control (IC50 = 49.73 ± 0.88 µM). Compounds 1 and 2 exhibited in vitro antioxidant activity with an IC50 value of 55.76 ± 1.30 and 59.36 ± 0.50 µM, respectively. However, the compound 3 didn't show obvious antioxidant activity.

Prognostic value of the microRNA-214 in multiple human cancers: a meta-analysis of observational studies.

Previous studies showed that microRNA-214 (miR-214) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. This study summarizes evidence and evaluates the prognostic role of miR-214 in various cancers. We carried out a systematic literature review and assessed the quality of included studies based on Oxford Centre for Evidence-based Medicine Criteria and Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for overall survival (OS) and disease free survival/progressive free survival/recurrence free survival (DFS/PFS/RFS) were calculated to measure the effective value of miR-214 expression on prognosis. Thirteen studies were included in pooled analysis. We found that miR-214 was significantly correlated with OS (HR=2.21, 95%CI: 1.33-3.68, P=0.00), no significant difference was found with DFS/PFS/RFS (HR=1.73, 95%CI: 0.78-3.83, P=0.18) in various carcinomas. In subgroup analysis, higher expression of miR-214 was significantly associated with poor OS in Asians (HR=2.27, 95%CI: 1.09-4.73, P=0.00) and Caucasians (HR=2.04, 95%CI: 1.47-3.30, P=0.00). On the contrary, high miR-214 expression significantly predicted favorable DFS/PFS/RFS (HR=0.50, 95%CI: 0.31-0.82, P=0.00) in hepatocellular carcinoma (HCC) group. Our data indicates that high miR-214 could be a promising biomarker for prognosis prediction of cancer. However, further clinical studies are needed for the current insufficient relevant data.