In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. Atherosclerosis results in the inner layer of the arterial wall and is characterized by local lipid accumulation and excessive production of collagen ,2,3. AthThe markers generally measured for diagnosing of atherosclerosis are lipid parameters of the blood, in particular cholesterol . Even thIt is well known that atherosclerosis develops asymptomatically affecting the intima which is non-innervated part of the arterial wall. Currently, asymptomatic  atherosclerosis is not an object of diagnostics and treatment while the number of clinical events on the background of asymptomatic atherosclerosis is quite high ,12,13. DA search for new reliable biomarkers of atherosclerosis is an important task . This reLipid deposition in the arterial wall is widely recognized as the earliest pathogenic event in preclinical atherogenesis . AtherogLDL is a lipoprotein fraction of particles that usually ranges in size of 18–28 nm and density of 1.019–1.063 g/mL . HoweverN-glycosylation sites. This protein is highly hydrophobic and hence remains with the lipoprotein particle throughout the metabolism [et al. [2-α1-β1-α2-β2-α3-COOH, showing the presence of two regions of amphipathic β-strands alternating with two regions of amphipathic α-helices and the third N-terminal amphipathic α-helical domain.The LDL particle contains a single apolipoprotein B-100 (apoB-100) molecule, 80–100 molecules of secondary proteins, approximately 3000 molecules of linoleic acids, 1500 molecules of esterified and non-esterified cholesterol (in average), and variable numbers of triglycerids and phospholipids composed mainly of phosphatidylcholine and sphingomyelin . In a ditabolism . ApoB-10tabolism . For the [et al. ,30 suggeN-terminal domain. However, apoB-48 is not able to bind to the LDL receptor since it lacks the LDL receptor-binding domain. The α3 α-helical region comprising 11% of apoB-100 is mobile and is involved in the control of availability of the LDL receptor-binding domain during the conversion of very low density lipoproteins (VLDL) to LDL in blood plasma [i.e., the entire α1α-helical region and 200 first amino acids of the β1 domain) were shown to form a three-dimensional structure that is similar to that of lipovitellin, an egg yolk lipoprotein containing a “lipid pocket” [In human serum, two major apoB isoforms (apoB-100 and apoB-48) exist. The apoB-48 isoform is produced after RNA editing of the apoB-100 transcript at residue 2180 resulting in the creation of a premature stop codon . Therefod plasma . The LDLd plasma . The fir pocket” . This “p pocket” .LDL receptors located on the surface (in clathrin-coated pits) of target cells are responsible for specific binding LDL particles followed by internalization of LDL-cholesterol through the mechanism of endocytosis . HepaticApart from transferring lipids, human VLDL and LDL are also suggested to be involved in intra-organismal protein transfer and delivering proinflammatory and prothrombotic protein mediators from the sites of synthesis to inflamed and embolic destinations ,38. For A single apoB molecule accounts for approximately 25% while lipids contribute for the remaining 75% of the molecular weight of the LDL particle . The hydLDL could be considered as a dynamic construct that needs to respond to changing environmental conditions during lipid exchange. Indeed, during particle remodeling, apoB and the surface phospholipids must rearrange to compensate for changes in the surface area and surface pressure . Within N-oxide (TMAO), and betaine, e.g., to catabolites that increase risk of atherosclerosis and cardiovascular disease [To date, over 350 various lipid species from 19 lipid subclasses were found in human LDL . Phospha disease .trans Golgi network. Sphingomyelin is involved in the regulation of endocytosis and receptor-mediated ligand uptake, in ion channel and G-protein coupled receptor function, in protein sorting, and function as receptor molecules for bacterial toxins and non-bacterial pore-forming toxins [Sphingomyelin is an essential structural component of serum lipoproteins and the second major phospholipid after phosphatidylcholine. Sphingomyelin is a prevalent sphingolipid in membranes of mammalian cells and this lipid class is specifically enriched in the plasma membrane, the endocytic recycling compartment, and the g toxins .2+-dependent sphingomyelinase by endothelial cells and macrophages that hydrolyses LDL sphingomyelin to ceramide (N-acetyl-d-sphingosine) [In inflammatory conditions such as atherosclerosis, proinflammatory mediators stimulate secretion of Znngosine) . Ceramidngosine) . In the ngosine) . Physiolngosine) .However, enrichment of LDL with ceramide is highly proatherogenic. Increase in LDL ceramide was found to increase the aggregation rate of LDL particles , to enhaet al., 2004). Compared to native LDL, electronegative LDL shows some proatherogenic characteristics including increased content of lysophosphatidylcholine (LPC) and presence of phospholipase C (PLC)-like activity of unknown origin [Electronegative LDL is a minor subfraction of modified LDL that is normally present in circulation   cholesterol seems to be the best predictor of the cardiovascular risk to date. Replacement of these parameters with a combination of lipid-related markers such as apoB and apoA-I, lipoprotein (a), or lipoprotein-associated phospholipase A2 does not improve cardiovascular disease (CVD) prediction but adding these markers to the combination of total cholesterol and HDL cholesterol slightly strengthen the prediction power . AlthougAlthough LDL binds to LDL receptor and oxidized LDL (oxLDL) binds to scavenger receptor, the vascular effects of minimally modified LDL and oxLDL are very similar . Both ofIn the pathologic conditions such as oxidative and metabolic stress, hyperlipidemia and/or diabetic hyperglycemia, circulating and intraintimal LDL are subjected to multiple enzymatic and non-enzymatic chemical modifications ,84,85. Ti.e., ability of blood sera from affected subjects to induce proatherogenic changes in the phenotype of cultured human aortic resident cells, monocytes, and macrophages [Modified LDL also possesses immunogenic properties and induces formation of autoantibodies ,90 that rophages . These aLDL-specific antibodies and their immune complexes with LDL could be detected not only in atherosclerotic plaques, but even in blood of apparently healthy children and newborns suggesting that proatherogenic risk factors may occur early in life ,93,94. I3+, Cu2+) are preferentially involved in oxidation of lipid constituents of LDL whereas myeloperoxidase and hypochlorous acid (HOCL) oxidize apoB-100 [LDL modifications and especially oxidation may play a key role in induction of atherogenesis. Non-oxidized LDL does not accumulate in macrophages while modified LDL does . OxLDL iapoB-100 . MyelopeapoB-100 . In oxLDapoB-100 .OxLDL can trigger inflammation through several mechanisms. In macrophages and monocytes, oxLDL induces fat deposits, ROS production, proinflammatory responses, and apoptosis ,101. In In endothelial cells, oxLDL stimulates expression of lectin-like oxLDL receptor-1 (LOX-1), which is up-regulated in atherosclerotic plaques and is implicated in several pathological processes that control lesion progression . OxLDL aet al. [et al. [Several studies supported good predictive and diagnostic value of oxLDL measured by a specific monoclonal antibody for atherosclerosis-related events including coronary and cerebral vascular disease. In a follow-up study of 326 clinically healthy Swedish men, Wallenfeldt et al.  showed a [et al.  observed [et al. . Overall [et al. . Except  [et al. ,110,111.N-terminus was shown to be essential for recognition of malondialdehide LDL (MDA-LDL) by a scavenger receptor of human monocytes/macrophages followed by receptor-mediated uptake of modified LDL [ROS degrade polyunsaturated lipids forming malondialdehide (MDA) . Indeed,fied LDL .In Japanese patients with CAD, a positive correlation between MDA-LDL levels measured by the ELISA method and coronary artery IMT and an inverse correlation between MDA-LDL and size of LDL particles was observed suggesting for association with coronary atherosclerosis ,117. Thevia mechanisms of non-enzymatic glycation and glycooxidation [In diabetic hyperglycemia, LDL can be intensively and irreversibly modified xidation . In the xidation . Small-dxidation . Glycatexidation ,124 and xidation .Formation of glycated LDL and other advanced glycation endproducts (AGEs) enhances atherogenic potential of circulating lipoproteins that are able to induce proatherogenic lipid uptake by cultured aortic SMCs  and stimet al. [In diabetic patients, association of increased glycated apoB levels with elevated triglycerids, a prevalent cardiovascular risk factor , and myoet al.  failed tet al. . Furtheret al. ,132,133.Carbamylation is the reaction between isocyanic acid HNCO with amines to give urea and other carbamides . MyelopeCarbamylated LDL are prone to further oxidation. Carbamylated-oxLDL are highly cytotoxic to endothelial cells ,142 and Carbamylated LDL are immunogenic inducing IgG autoantibodies in LDL-deficient receptor mice . These aSialic acid is an essential component of native LDL representing the terminal carbohydrate of biantennary sugar chains in apoB and carbohydrate chains in gangliosides . DesialyAfter desialylation, the monosaccharide residue  that precedes the syalic acid in the carbohydrate chain becomes terminal and externally exposed. Galactose has high affinity to lectins. Up to 80% of the electronegative LDL is bound to lectin, a phenomen allowing quantification of these LDL in blood using a lectin-sorbent assay  and specThe electronegative desialylated LDL subfraction is highly proatherogenic since is able to enhance cholesterol deposits by 2- to 4-fold in cultivated normal aortic cells . A minoret al. [2+-mediated oxidation, Tanaka et al. [et al. [Tertov et al.  consideret al. . In humaa et al.  observed [et al.  observed [et al. . Under i [et al. .i.e., small size, higher density, higher electronegative charge, lowered content of sialic acid, increased oxysterol levels, and similar content of lipid peroxides [The desialylated subfraction of LDL is highly immunogenic and induces production of proatherogenic IgG self-antibodies that may contribute to atherogenesis by increasing the uptake of LDL by aortic cells . Furthereroxides ,168.in vitro cannot be retrieved in the blood. Despite the huge amount of work on the role of oxidized LDL in atherogenesis neither oxLDL nor MDA-LDL were detected in the blood. Indeed, LDL oxidation is likely to occur not in the blood but in the vascular wall. Circulating mmLDL were found to display signs of oxidation but oxidation is one of the various modifications occurred in the lipoprotein particle [in vitro-generated oxLDL cannot be retrieved in the blood. On the other hand, at least four forms of atherogenic LDL modifications were detected in the blood of patients such as small dense LDL, electronegative LDL, glycated LDL (in diabetic patients), and desialylated LDL.Certain species of oxLDL that are artificially generated particle . Therefoi.e., they are small dense lipoprotein particles [i.e., it was desialylated LDL. These data demonstrate the similarity of the two types of modified LDL. Atherogenic LDL subfraction isolated from the blood of diabetic patients represents small-dense, glycated, and desialylated lipoprotein particles [Electronegative LDL , small darticles . On the articles  isolatedarticles . These aEx vivo experiments have revealed mechanisms of multiple modification of LDL in the blood. Fraction of native LDL was isolated from blood plasma. In addition, blood serum of patients with documented atherosclerosis was obtained. LDL and serum was mixed and incubated for various periods at 37 °C. It was found that even after one-hour incubation of native LDL with atherogenic serum subfraction of desialylated LDL appears [ appears . After t appears . In the Modified LDL are well known to induce an adaptive immune response in atherosclerosis associated with production of self-antibodies specific to modified LDL . AlthougA spectrum of circulating anti-LDL antibodies may greatly vary depending on the pathological conditions. For example, the majority of IgG fraction of anti-LDL antibodies isolated from blood of type 2 diabetic patients were specific to MDA-LDL (>70%) followed by anti-AGE-LDL antibodies. Trace levels of antibodies against carbamyl-LDL, LDL modified by myeloperoxidase-dependent oxidation, and (hexanoyl) lysine-LDL (a product of reaction of linoleic acid hydroperoxide and lysine) could be also detected .Anti-LDL antibodies specific to various types of modified LDL may be cross-reactive between each other suggesting for presence of shared epitopes. For example, AGE-LDL antibodies that are primarily reactive with AGE-LDL show cross-reactivity with MDA-LDL and carbamyl-LDL due to the presence of carbamylated lysine epitopes in MDA-LDL .in vivo. In blood, anti-LDL autoantibodies were first detected by Palinski et al. [in vivo [Detection of antibodies against MDA-LDL is often regarded as evidence of the existence of oxLDL i et al. . The auti et al.  have est[in vivo . Somewha[in vivo ,178. MorIt was found that also MDA-LDL reacts with anti-LDL with similarly high affinity as LDL from patients. Thus, it was confirmed that affinity of autoantibodies to MDA-LDL is higher compared to that to native LDL. However, autoantibodies had the highest affinity to desialylated LDL. Affinity constant of autoantibodies to desialylated LDL was an order higher than to MDA-LDL and two orders higher than to native LDL . Thus, aet al. [Circulating self-antibodies against LDL can be useful as diagnostic and prognostic markers of cardiovascular risk. Doo et al.  showed tet al. . Similaret al. ,181.et al. [For MDA-LDL antibodies, in a large prospective epidemiologic European Prospective Investigation into Cancer (EPIC)-Norfolk Study including non-selected and initially healthy population, levels of IgG and IgM antibodies were shown to predict risk of CAD events but this risk is modulated by oxidative markers. Anti-MDA-LDL antibodies showed an inverse correlation with CAD events suggesting for their atheroprotective role . The athet al. .etc. [However, there are studies that do not support the prognostic value of anti-LDL antibodies for cardiovascular events. The significant discrepancy in results can be explained by difference in selection criteria used to recruit patients, heterogeneity of groups of patients tested, difference in protocols used to purify antibodies, lack of standardization in antibody-detecting immunoassays, small numbers of patients studied, etc. . In factin vitro by copper oxidation or with help of horseradish peroxidase (HRP) are commonly used as antigens to induce antibody production. However, anti-copper-oxLDL antibodies displayed no cross-reactivity with anti-HRP-oxLDL-antibodies [Streptococcus pneumoniae were detected [The diagnostic value of anti-oxLDL antibodies in atherosclerosis is seriously limited by several obstacles. The lack of standard protocols in measuring serum titers of anti-oxLDL antibodies is likely to represent the major reason of inconsistent results produced by different groups . Ox-LDL tibodies  that coudetected  and measdetected . Finallydetected ,189.Kd = ~10−8 mol/L) had higher affinity than free MDA-LDL antibodies circulating in the bloodstream (Kd = ~10−7 mol/L) [Anti-LDL antibodies can indeed form immune complexes with modified LDL that circulate in the blood. Interestingly, MDA-LDL antibodies isolated from the immune complexes (7 mol/L) . Indeed,7 mol/L) ,190. Ind7 mol/L) .et al. [in vitro from radiolabeled LDL and anti-apoB IgG. Morphologically, macrophages incubated with lipoprotein-containing CICs display an appearance of typical foam cells /Diabetes Control and Complications Trial (DCCT) comprising 1050 diabetic individuals . Recentlet al.  reportedet al. .vs. the patients at the lowest quartile) compared with MDA-LDL and AGE-LDL [Quantification of LDL subfractions in the circulating immune complexes derived from sera of 473 type 1 diabetic patients revealed strong association of MDA-LDL and AGE-LDL with IMT after adjustment for conventional risk factors suggesting for a robust predictive value of both parameters for progression of carotid atherosclerosis in type 1 diabetes ,214. Fur AGE-LDL . The sig AGE-LDL . MDA-LDL AGE-LDL .n = 58), hypercholesterolemic coronary heart disease (CHD)-free study participants with serum cholesterol above 250 mg/dL (n = 134), and the patients with clinically manifested atherosclerosis in the form of CHD and/or personal history of myocardial infarction (n = 138). The interquartile range of proportion of mmLDL accounted for 10%–25% of a total serum apoB-containing LDL  in atherosclerosis. On the basis of clinical and laboratory examination, the study participants were divided into three groups: asymptomatic low-risk study participants . It is notable that the correlation was more pronounced than in the case of LDL-containing CICs [r = 0.349, p < 0.001) was also revealed in this study. These results were considered as the indication of the role of mmLDL both in formation of serum atherogenic potential and LDL-CICs. The two-fold increase in proportion of multiple modified LDL was observed in hypercholesterolemic patients as compared to low-risk study participants (p < 0.001); in patients with clinically manifested atherosclerosis the proportion of mmLDL was comparable to low-risk study participants, possibly due to the effects of intensive therapeutic interventions.The direct correlation was found between the proportion of mmLDL and the ability of serum to induce lipid accumulation in cultured blood-derived monocyte-macrophages (ing CICs ,211,212.The results of this study suggest that the diagnostic and prognostic significance of mmLDL is at least not lower than that of LDL-containing CICs.In atherosclerosis, blood LDL are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity ,166,172.Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation and atherogenesis itself. Compared to freely circulating modified LDL, modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Importantly, various lipid components of the immune complexes may serve, not only as diagnostic, but also as essential predictive markers of cardiovascular events in atherosclerosis ,211,212.In conclusion, the accumulating evidence indicates that the quantification of modified LDL associated with immune complexes has a predictive value superior of that of traditional risk markers that are currently in use ,211,212.


Background. Huachansu, the sterilized water extract of Bufo bufo gargarizans toad skin, is used in China to alleviate the side-effects and enhance the therapeutic effect of chemotherapy in advanced non-small-cell lung cancer (NSCLC). We conducted a meta-analysis to assess Huachansu's efficacy. Methods. We extensively searched electronic databases  for randomized controlled trials containing Huachansu plus chemotherapy as the test group and chemotherapy as the control group. Seventeen trials were selected based on the selection criteria. The pooled relative ratio (RR) of indicators with 95% confidence interval (95% CI) was calculated for efficacy evaluation. Results. The meta-analysis demonstrated a statistically significant improvement in objective tumor response, one-year survival, Karnofsky performance status, pain relief, and alleviation of severe side-effects  in the test group as compared to the control group, but no significant difference in thrombocytopenia. Conclusions. This study demonstrated the efficacy of Huachansu combined with chemotherapy in the treatment of advanced NSCLC. However, limitations exist and high-quality trials are needed for further verification. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, which is difficult to diagnose in early stages. Patients diagnosed with advanced NSCLC are often unable to undergo surgery, thus reducing the survival time . So far, Bufo bufo gargarizans toad skin [ Bufo bufo gargarizans a valuable source of traditional Chinese medicine (TCM) [Huachansu (Cinobufacini) is the sterilized water extract ofoad skin , a smalload skin . These ioad skin . Moreoveoad skin , 6, whicne (TCM) , 8. The ne (TCM) .In order to alleviate the side-effects of chemotherapy and enhance therapeutic efficacy in advanced NSCLC, several clinical studies have been conducted using Huachansu combined with chemotherapy to observe whether this would be beneficial for patients. But due to the limited scale of these studies, certain results remain inconsistent. Therefore, we performed a meta-analysis by pooling the randomized clinical trials to evaluate the efficacy of this complementary therapy.Clinical trials were retrieved from the Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; Cochrane Library; Chinese Biological Medicine Database (CBM); China National Knowledge Infra-Structure Database (CNKI); Chinese Evidence-Based Medicine Database (CEBM); Wan Fang Digital Periodicals Database (WFDP); China Science Citation Database (CSCD); Chinese Science Technology Document Database (CSTD); and the International Pharmaceutical Abstracts (IPA), from their inception to January 2015. The retrieval terms used were as follows:  AND (Huachansu OR Hua chan su OR Cinobufacini).Studies that met the following criteria were included: (1) type of studies: clinical randomized controlled trials (RCTs); (2) participants: age ≥18 years with pathology and CT diagnosis of NSCLC in stage III or IV with detectable solid tumor and KPS ≥60; (3) type of intervention: treatment with Huachansu combined with chemotherapy as the test group; (4) type of outcome: reports with at least one of the following indicators: objective tumor response, one-year survival, quality of life , pain relief, major drug adverse reactions, or the data necessary to calculate them. Clinical trials were excluded if they did not meet the above criteria. The following types of studies were also excluded: (1) treatment without chemotherapy as the control group; (2) nonoriginal or duplicated publications; (3) patients with other serious illnesses.All reports were independently reviewed by two reviewers (BD Zhou and FY Wu) to evaluate their quality, decide which study would meet the eligibility criteria, and extract the data needed: author names, year of publication, study type, patient information, details of the treatment, and outcome. Any disagreements were resolved through discussion or by a third reviewer.p < 0.05 was considered to be statistically significant. To determine whether the random-effects or fixed-effects model should be used, the I2 was used to estimate heterogeneity (random-effects model when I2 ≥ 50% or fixed-effects model when I2 < 50%) [The STATA (version 11.0) was used for data analysis. Relative ratio (RR) and 95% confidence intervals (CI) were calculated. 2 < 50%) .The indicators for evaluation of therapeutic efficacy were as follows: (1) objective tumor response; (2) one-year survival; (3) improved performance status; (4) pain relief; (5) symptoms of severe side-effects caused by chemotherapy .In this study, seventeen trials were selected based on selection criteria. A total of 80 publications were originally identified, of which 63 studies were excluded and 17 studies were finally included based on the selection criteria with 1142 enrolled patients (578 in the test group and 564 in the control group) –26. The All 17 studies mentioned random allocation, but only six studies described random allocation methods. No study described the blind method and allocation concealment. All patients recruited in these studies were diagnosed at stages III to IV NSCLC TNM. These patients were given an overall physical assessment before treatment, including age, quality of life score, and stage of disease. No significant differences between the baseline data were reported and all patients were estimated with life expectancy ≥3 months. Different combination chemotherapies were used for treatment: vinorelbine plus cisplatin (NP), docetaxel plus cisplatin (DC), paclitaxel plus cisplatin (TP), gemcitabine plus cisplatin (GP), etoposide plus cisplatin (EP), vinorelbine plus carboplatin (NC), vinorelbine plus ifosfamide (NI), and pemetrexed plus cisplatin. The methodological quality was evaluated using the Jadad scale according to the description in these reports on randomization, blinding method, withdrawals/dropouts, and allocation concealment, which was presented in p < 0.0001, 879 patients). A fixed-effects model was used since heterogeneity was absent  , partial response (PR), stable disease (SD), and progressive disease (PD) in each group, based on the WHO scale. The objective tumor response was determined by the number of patients with CR plus PR. Meta-analysis showed a significant increase in the number of patients with CR plus PR in the Huachansu plus chemotherapy test group  .p = 0.007, 262 patients). As heterogeneity was absent , a fixed-effects model was used . Since heterogeneity was absent , a fixed-effects model was used , stable status (an increase or decrease of <10 points), and decline status (a decrease of ≥10 points) in each group based on the Karnofsky performance scale (KPS). Meta-analysis showed a significant increase in the number of patients with improved status in the test group . Since heterogeneity was absent , a fixed-effects model was used . A fixed-effects model was used, as the heterogeneity was not significant  . Since no heterogeneity was observed , a fixed-effects model was used . As heterogeneity was absent , a fixed-effects model was used . Meta-analysis showed a significant reduction in the number of cases in the test group as compared to the control group  . Nine trwas used . Five trwas used .p value increased for certain indicators when using the random-effects model, the outcomes did not change. The results are displayed in The fixed-effects and random-effects models were used to perform sensitivity analysis. Though the p = 0.036). No bias was observed in the other groups. The results are displayed in Begg's funnel plot and Egger's linear regression test were used to evaluate the publication bias. The result of Egger's test suggested a publication bias among the studies within the group of thrombocytopenia  and indole alkaloids . Experiments have shown that Cinobufagin, Resibufogenin, and Bufalin strongly inhibit tumor cells, and Bufotenine, Cinobufotenine, and Serotonin can act on the neural system [This meta-analysis showed that Huachansu can increase the objective tumor response and one-year survival, improve performance status, alleviate severe chemotherapy side-effects, and relieve cancer pain, which may be attributed to the various ingredients in Huachansu, which is just like a troop equipped with multiple weapons. So far, more than 30 ingredients have been identified in the skin secretion ofl system , 28. TheIn summary, this meta-analysis suggests that Huachansu, as a natural medicine containing many active ingredients, can be a promising supplement to routine chemotherapy in treating advanced NSCLC. However a major limitation of this study is the low methodological quality of the included reports. Therefore, more high-quality trials are needed in the future to validate these findings. Besides, to avoid publication bias, the likelihood of publication of trials should in no way depend on whether the results were positive or negative.


N = 554 was surveyed. Data were analysed with correlation and multiple regression analyses and dependent t-tests. Over-reporting of handwashing was associated with factors assumed to be involved in (1) socially desirable responding, (2) encoding and recall of information, and (3) dissonance processes. The latter two factor groups explained over-reported handwashing beyond socially desirable responding. The alternative interview question—script-based covert recall—reduced over-reporting compared to conventional self-reports. Although the difficulties involved in measuring handwashing by self-reports and observations are widely known, the present study is the first to investigate the factors which explain over-reporting of handwashing. This research contributes to the limited evidence base on a highly important subject: how to evaluate handwashing interventions efficiently and accurately.Handwashing interventions are a priority in development and emergency aid programs. Evaluation of these interventions is essential to assess the effectiveness of programs; however, measuring handwashing is quite difficult. Although observations are considered valid, they are time-consuming and cost-ineffective; self-reports are highly efficient but considered invalid because desirable behaviour tends to be over-reported. Socially desirable responding has been claimed to be the main cause of inflated self-reports, but its underlying factors and mechanisms are understudied. The present study investigated socially desirable responding and additional potential explanatory factors for over-reported handwashing to identify indications for measures which mitigate over-reporting. Additionally, a script-based covert recall, an alternative interview question intended to mitigate recall errors and socially desirable responding, was developed and tested. Cross-sectional data collection was conducted in the Borena Zone, Ethiopia, through 2.5-hour observations and 1-hour interviews with the primary caregivers in households. A total sample of  Diarrheal diseases and acute respiratory infections are the main causes of death among children younger than 5 years old throughout the world  and are However, measuring handwashing behaviour can be quite difficult , 12, 13.Self-reported handwashing can be collected easily and efficiently through interviews , 12. Howand valid self-report measures of handwashing. Therefore, the main aim of the present study was to investigate socially desirable responding and additional potential explanatory factors for the bias between self-reported and observed handwashing behaviour. The research questions were whether socially desirable responding and other factors are associated with over-reported handwashing and whether additional factors beyond socially desirable responding explain over-reporting. In addition, we investigated whether an alternative self-report measure thought to reduce the influence of socially desirable responding and additional factors mitigates the response bias. In the following section we discuss potential sources of over-reported handwashing and deduce corresponding hypotheses.In sum, the measurement of handwashing behaviour is a major challenge for intervention evaluations as observations are considered valid but cost-ineffective and self-reports cost-effective but invalid , 13. AltA response might be biased as (1) the response was edited , (2) theH1: The higher the tendency to respond in a socially desirable manner is, the higher over-reporting of self-reported handwashing is.H2: The higher the need for conformity is, the higher over-reporting of self-reported handwashing is.H3: The higher the feeling of group attachment is, the higher over-reporting of self-reported handwashing is.Socially desirable responding is one of the most commonly studied forms of response editing and response biases . First, H4: The stronger the perceived social norms that favour handwashing are, the higher over-reporting of self-reported handwashing is.Second, socially desirable responding also depends on the sensitivity of a questionnaire’s topic, in other words, whether a clear social norm regarding the behaviour or attitude at hand exists . What isQ1: Is the presence of a spouse during the interview associated with over-reporting of self-reported handwashing?Q2: Is the presence of other adults during the interview associated with over-reporting of self-reported handwashing?Third, if a question is sensitive, the level of privacy or confidentiality offered in an interview influences socially desirable responding , 28. TheH5: A regular daily household routine is associated with less over-reporting of self-reported handwashing than an irregular daily household routine.H6: The more frequently tasks are interrupted, the higher over-reporting of self-reported handwashing is.Regarding inaccurate memory formation and recall errors, a first factor potentially distorting the encoded handwashing frequency is forgetting to wash hands at a certain moment. Compared to forgetting other health behaviours, forgetting to wash hands at a certain moment stands out as it might never become salient at any moment to individuals. Respondents might not realize how often they intended to but forgot to wash their hands; therefore, the encoded handwashing frequency might be biased against the actual amount and towards the intended amount. Regular daily routines facilitate and frequent task interruptions impede remembering and implementing intended behaviours , so we aH7: The more a person tends to over-estimate, the higher over-reporting of self-reported handwashing is.Regarding further recall errors, memory performance varies among people; some people perform better than others at a variety of memory tasks , 34. It H8: The higher handwashing-related health knowledge is, the higher over-reporting of self-reported handwashing is.H9: The higher cognitive rationalisation of neglected handwashing is, the lower over-reporting of self-reported handwashing is.H10: Health knowledge and rationalisation interact with the highest over-reporting found for high health knowledge and low rationalisation and with the lowest over-reporting found for low health knowledge and high rationalisation.Returning to information formation, a further factor that might increase encoding inaccuracy is cognitive dissonance, a state of psychological tension felt when one’s cognitions (e.g. knowledge or attitudes) and/or behaviour are dissonant . RegardiH11: Script-based covert recall produces less over-reporting than action-based prompted recall (i.e. a standard self-report measure).When factors that largely explain over-reporting are found, the response bias can be addressed by improving interview questions accordingly . To mitiTo sum up, the present study investigated (1) whether socially desirable responding, inaccuracies in encoding, recall errors and dissonance processes are associated with over-reporting of handwashing; (2) whether the latter processes explain over-reporting beyond socially desirable responding; and (3) whether an alternative self-report measure reduces over-reported handwashing. To address these research questions, a cross-sectional study that combined observational and self-reported data was conducted in Ethiopia.The study was conducted as part of a larger research project investigating handwashing in four Borena kebeles  in southern Ethiopia. The Borena Zone is a semi-arid region which suffers repeated droughts. Governmental and non-governmental organisations have implemented handwashing interventions in the Borena Zone as part of drought responses since 2006.Each of the four study kebeles consisted of approximately 30 hamlets, and only those that were reachable by car or a maximum 20-minute walk were included in the study. Within a hamlet, households were selected by the random-route method . The elin = 71 for the key time of wiping a child’s bottom).According to sample size estimation with G*Power 3.1 , a samplThe present study was interested in factors associated with over-reporting of handwashing and measures to mitigate it. This focus necessitated a comparison of observed and self-reported data, and to maximise comparability, a cross-sectional correlational design measuring all the variables at one point in time seemed appropriate.Data collection took place in February and March 2013 through 2.5-hour observations and 1-hour, oral, face-to-face interviews. Observations took place at dawn or around noon during lunch preparation and were followed by interviews. Data were collected by 14 local students and social workers, of whom two were female and 12 male. To ensure high quality in data collection, the team received extensive training in a 4-day workshop. The workshop included an introduction to different question types, demonstrations of how to ask the different question types, a discussion of what to do and what not to do during interviewing and observations  judging responses or behaviour, and lecturing the participant). In addition, the workshop offered a question-by-question discussion of the questionnaire and extensive practice in conducting the interview and the observational procedure through role playing. To ensure that data collection was conducted as in training, the first author, a local research collaborator and a postgraduate student supervised the team during data collection.http://www.apa.org/ethics/code/) and the World Medical Association (WMA) Declaration of Helsinki (http://www.wma.net/en/30publications/10policies/b3/). It was part of a larger research project on handwashing which received ethical approval from the Ethiopian National Research Ethics Review Committee and the Ethics Committee of the Philosophical Faculty of University of Zurich. Following approval from these ethics boards, oral informed consent was obtained from all study participants. Written consent could not be obtained because of the high illiteracy rate in the sample. When a selected household refused to participate in the study, the household members were thanked, and the research team members left immediately. The number of refusing households was recorded in a dedicated space in the questionnaire of the next consenting household.This study was conducted in strict compliance with the ethical principles of the American Psychological Association .The interviews were based on a structured questionnaire developed for this study. The items covered socio-demographic characteristics, self-reported handwashing (standard measure), potential explanatory factors and alternative self-report measures of handwashing. Most of the response options used Likert scales , which were transformed into a value range of 0–1 (or -1–1 for bipolar items) to facilitate interpretation. The questionnaire was prepared in English, translated into Afan Oromo and then retranslated into English to ensure the quality of the translation. A structured format was prepared for observations . The appbefore eating/after defecation?’ . Th10 times : after d10 times . This finstool = 24 and nfood = 17) as only a few participants were observed at all respective key times; therefore, internal consistency could not be conclusively assessed. Response scales ranged from 0 = 0% handwashing to 1 = 100% handwashing.The same key times measured by self-reports were observed. If a key event occurred, it was noted in a structured format, along with whether both hands were washed with water before or after the event separately and whether soap was used. During data processing, for each respondent and for each type of key event (e.g. food preparation) the percentage of times a participant washed both hands with soap at a key event out of all the times the key event occurred was calculated. To allow for direct comparison with self-reported data, observational data concerning faeces and food were averaged to form observed stool- and food-related handwashing, although internal consistency was rather low . However, these estimates were based on very small samples , the items were averaged according to the original short form C )actual effects on over-reporting in isolation from the influence that the factors  might have also had on actual behaviour and thus responding. Whether observed behaviour is the most valid measure for actual behaviour and, thus, the standard of comparison for other measures can be questioned. However, answering this question was not within the scope of the present study.The present study assessed over-reporting directly by subtracting observed from self-reported behaviour scores. Consequently, we could investigate the explanatory factors’ In the present study, care was taken to ensure the comparability of the measures used for observed and self-reported behaviour to the greatest extent possible. Self-reported and observed behaviour were measured on the same day, and comparable response scales in interviews and recording formats in observations were employed. While the worth of comparability seems rather basic, previous studies that compared self-reported and observed behaviour used answer scales and observation formats that were not comparable e.g. , 17, 19), 1917, 1Still, some factors limited comparability in the present study. Observations lasted for only 2.5 hours because the usual daily routines of primary caregivers in the studied region rarely left them at home for more than 3–4 hours at a time. Within 2.5 hours, repeated observation of one key time (e.g. food preparation) was rare. Accordingly, handwashing compliance at a specific key time was often determined by a single observation event. Self-reports, in contrast, asked for an integrated estimation of handwashing frequency at a key time. Future studies investigating over-reporting of handwashing should attempt to further increase the comparability between self-reported and observation measures.A further limitation of the present study is that some factors were tested even though the internal consistency of their measures was insufficient . The internal consistency of the observation measures was also not conclusively assessed. The internal consistency of these measures requires further investigation.Several of the assumed underlying mechanisms were not tested directly, in particular, dissonance processes and the influence of unnoticed forgetting of washing hands on over-reporting. In addition to the idea for future research regarding forgetting already mentioned, dissonance processes could be investigated through experimental research testing whether the induction of dissonance  increases over-reporting .Though many factors were considered in the present paper, several factors were not included even though they might affect over-reporting of handwashing . Although some of these are rather unlikely to be relevant given the response patterns found in the present study (e.g. acquiescence tendency), the factors should be investigated in subsequent studies.An additional aspect which is essential to measurement but was not considered in the present paper is reliability; a measure’s consistency or repeatability. Previous studies have questioned the inter-rater and retest reliability of observed handwashing in both household and hospital settings , 61, 62.The difficulties involved in measuring handwashing by self-reports and observations, including over-reporting of self-reported handwashing, are widely known. The present paper is the first to investigate explanatory factors for over-reporting of handwashing. This study also tested measures to mitigate over-reporting. This research has contributed to the limited evidence base for a complex phenomenon and a highly important subject: how to evaluate handwashing interventions efficiently and accurately. We hope that the present paper stimulates further research on over-reporting of handwashing and on alternative self-report measures to mitigate response bias.S1 FileM) and standard deviations (SD) of socio-demographic characteristics for inconsistent and consistent stool-related hand washers and related t-tests (Table A). Frequencies in socio-demographic characteristics for inconsistent and consistent stool-related hand washers and related χ2-tests (Table B). Means (M) and standard deviations (SD) of socio-demographic characteristics for inconsistent and consistent food-related hand washers and related t-tests (Table C). Frequencies in socio-demographic characteristics for inconsistent and consistent food-related hand washers and related χ2-tests (Table D). Means (M) and standard deviations (SD) of socio-demographic characteristics for consistent stool-related hand washers and consistent food-related hand washers and related t-tests (Table E). Frequencies in socio-demographic characteristics for consistent stool-related hand washers and consistent food-related hand washers and related χ2-tests (Table F).Means ((PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.


Although recent studies have improved understanding of quality of life (QOL) outcomes of breast conserving surgery, few have used longitudinal data for more than two time points, and few have examined predictors of QOL over two years. Additionally, the longitudinal data analyses in such studies rarely apply the appropriate statistical methodology to control for censoring and inter-correlations arising from repeated measures obtained from the same patient pool. This study evaluated an internet-based system for measuring longitudinal changes in QOL and developed a cloud-based system for managing patients after breast conserving surgery.This prospective study analyzed 657 breast cancer patients treated at three tertiary academic hospitals. Related hospital personnel such as surgeons and other healthcare professionals were also interviewed to determine the requirements for an effective cloud-based system for surveying QOL in breast cancer patients. All patients completed the SF-36, Quality of Life Questionnaire (QLQ-C30) and its supplementary breast cancer measure (QLQ-BR23) at baseline, 6 months, 1 year, and 2 years postoperatively. The 95% confidence intervals for differences in responsiveness estimates were derived by bootstrap estimation. Scores derived by these instruments were interpreted by generalized estimating equation before and after surgery.All breast cancer surgery patients had significantly improved QLQ-C30 and QLQ-BR23 subscale scores throughout the 2-year follow-up period (p<0.05). During the study period, QOL generally had a negative association with advanced age, high Charlson comorbidity index score, tumor stage III or IV, previous chemotherapy, and long post-operative LOS. Conversely, QOL was positively associated with previous radiotherapy and hormone therapy. Additionally, patients with high scores for preoperative QOL tended to have high scores for QLQ-C30, QLQ-BR23 and SF-36 subscales. Based on the results of usability testing, the five constructs were rated on a Likert scale from 1–7 as follows: system usefulness (5.6±1.8), ease of use (5.6±1.5), information quality (5.4±1.4), interface quality (5.5±1.4), and overall satisfaction (5.5±1.6).The current trend in clinical medicine is applying therapies and interventions that improve QOL. Therefore, a potentially vast amount of internet-based QOL data is available for use in defining patient populations that may benefit from therapeutic intervention. Additionally, before undergoing breast conserving surgery, patients should be advised that their postoperative QOL depends not only on the success of the surgery, but also on their preoperative functional status. Recent years have seen an increased incidence of breast cancer in Taiwan. Women in the early stages of breast cancer generally have three equally effective surgical options: breast conserving surgery (BCS), modified radical mastectomy (MRM), or mastectomy with reconstruction (TRAM) , 2. HoweAlthough the growing considering of QOL outcomes for breast cancer after surgery, previous studies suffer from several major shortcomings –4. FirstThere are some pros and cons between cloud-based systems and a traditional off-line system. We argued these differences in several perspectives: cost, data process, time and place. First, offline systems generally need to consider the additional spending of personnel and material cost. We need to follow up more times via phone or mail card to guarantee the proper response rate. Conversely, cloud-based system improved the survey efficiency via information communication technology assistance . Second, cloud-based system had less constrain for the data processing than off-line survey (e.g. paper questionnaire). We could get aggregated, integrated, secure data, and downloading from the cloud easily. We did not re-enter data from paper-based questionnaire and reduced the probability of type error. Finally, cloud-based design allows you and your respondent easy access to applications and data from different computers and devices. Meanwhile, cloud applications are browser-based and users are accessible easily from mobile devices, such as tablets and smartphones. Once users register in the cloud, they can access the information from anywhere and anytime. In sum, the cloud-based survey benefits outweighed paper surveys because it ensured wide publication, immediate access, relative speed, and little to no data input or manipulation.CSIS-BCP) was then developed to improve the efficiency, agility and usability of survey research, but also to allow healthcare providers and breast cancer patients to easily and conveniently access necessary information. Cloud-computing services offer a distinct advantage in that they allow individuals and organizations to outsource all technology management and maintenance tasks to an expert third party, and to defray expensive equipment purchases, thus providing an extremely cost-effective solution for on-demand services. In the present context, using cloud computing environments also increases accessibility to large amounts of data, thus creating synergies and advantages over conventional methods of investigation and analysis.This large-scale prospective cohort study applied generalized estimating equations (GEE) to study QOL changes in a population of women who had received breast cancer surgery. Compared to other prediction methods, GEE is more effective and more precise for predicting QOL changes after breast cancer surgery , 2. A clThis study was approved by the research ethics boards of Kaohsiung Medical University Hospital, Kaohsiung Veterans General Hospital and Chi Mei Medical Center where this study was located. All cloud-based QOL questionnaires were directed by the same two research assistants before and after surgery. The research assistants fully explained the procedures to all of the participants, from whom written informed consent was obtained before enrolling in the study.CSIS-BCP database to support further analysis of QOL in the breast cancer surgery patients.Quality of life in breast cancer surgery patients was investigated by interviewing related stakeholders such as surgeons, patients, and other healthcare professionals. The interview results were then entered into the CSIS-BCP. First, the cloud resource manager dynamically deploys virtual machines to process raw data from the respondents. Second, the information extractor retrieves, transforms, clips and merges the processed data from the database management system (DBMS) according to user instructions. Third, the presenter provides a convenient user-friendly interface that enables users to issue query instructions to the CSIS-BCP and to view the data retrieved from the cloud system. The CSIS-BCP currently supports four main functions. For a specific breast cancer patient, CSIS-BCP supports the entry, querying, and display of QOL data. For two or more breast-cancer patients, the CSIS-BCP enables comparisons of QOL data [CSIS-BCP for analyzing QOL trends in a given patient and comparing QOL with that of other patients.QOL data , 6. ThisWe designed the application processing interface (API) and it included four major components : applicaThe sample for this study was taken from a pool of 657 patients with incidental breast cancer and was treated between August 2010 and September 2012 at three medical centers in southern Taiwan. Patients without metastasis were informed of surgical options . Patients with benign tumors (n = 149) or cognitive impairments (n = 4), were excluded, leaving 504 patients . Over thCSIS-BCP, between August and September 2013, 60 stakeholders participated in a system usability assessment.Prior to surgery, the participating physicians and researchers administered the cloud-based QOL questionnaire survey at the hospital. At 6 months, 1 year, and 2 years after surgery, the participants completed the survey at home or in the hospital during clinical visits. Following implementation of the The QLQ-C30 and QLQBR23 questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC) were used to assess QOL. The EORTC QLQ-C30 is a generic QOL measure for cancer patients which comprises a global health status/QOL subscale, five multi-item functional subscales , and several single/multi-item symptomatic subscales . All Likert scale scores  were linearly transformed into scores of 0–100 where higher scores indicate better functional status or worse symptomatic problems. The EORTC QLQ-BR23 measures aspects specific to breast cancer and comprises 23 items distributed among four functional subscales  and five symptomatic subscales . Chinese versions exist for the EORTC QLQ-C30 and EORTC QLQ-BR23, and these have been successfully used for studies of Taiwanese breast cancer patients . Most ofMany studies have used the SF-36 to profile generic QOL as it allows researchers to compare patients suffering from different diseases in different countries , 2. To pThe following patient data obtained by medical record reviews and questionnaire interviews were tested as independent variables in this study: age, education, living with immediate family, body mass index (BMI), number of pregnancies, breast cancer history, other breast disease history, Charlson co-morbidity index (CCI), tumor stage, surgical procedure, American Society of Anesthesiologists (ASA) class, chemotherapy, radiotherapy, hormone therapy, post-operation length of stay (LOS), post-hospitalization 30-day complications, and preoperative functional status .The unit of analysis was the individual breast cancer surgery patient in this study. First, descriptive statistics were tabulated to produce demographic profiles of the patients. Longitudinal data analysis was based on multiple observations, showing high variability between subjects but low variability within subjects. Ordinary regression methods assume observational independence and thus were not well suited for analyzing longitudinal relationships, given this high within-subject correlation.The GEE approach was used to explore Longitudinal changes in each QOL subscale were examined using GEE and survey data from four time points: prior to surgery, and 6-month, 1-year and 2-year post-op. Each QOL subscale was used as a dependent variable as a function of time and effective covariates, which included age, BMI, average LOS, tumor stage, chemotherapy, radiotherapy, hormone therapy, and preoperative functional status. While similar to a repeated-measures analysis of variance, GEE can compensate for incomplete data at multiple assessment points without creating conflicts with the remaining data, making it particularly useful for dealing with incomplete data in longitudinal studies with continuous outcomes. Autoregressive GEE analysis was used to analyze longitudinal associations when using data for more than two time points.CSIS-BCP. Lewis’ Post-Study System Usability Questionnaire (PSSUQ) was used to assess the information system in terms of user satisfaction and usability [The recent literature defines usability as effectiveness and efficiency in providing user satisfaction and in assisting the user in achieving his/her specific goals . Here, asability . The PSSα of 0.05, a power of 80%, and an inter-temporal between-score correlation of 0.80.In this study, statistical analyses were executed using Stata Statistical Package, Version 10.0 . The sample size in this study was sufficient to detect a 5-point difference over time in all QOL subscales, assuming an th and 24th month after discharge did not statistically differ in terms of age, education, living with immediate family, BMI, number of pregnancies, breast cancer history, other breast disease history, CCI score, tumor stage, surgical procedure, ASA class, chemotherapy, radiotherapy, hormone therapy, post-operation LOS, 30-day post-hospitalization complications, or preoperative functional status.Subjects who remained in the study throughout the 2-year period and those who were lost to follow up between the 6The mean age of the study population was 52.21 (± 9.59) years . On averP < 0.01) and then remained stable for the rest of the two-year period. When using the sixth month after discharge as a baseline, all QOL subscales other than that for global quality of life were significantly improved by the first year after discharge (P < 0.05). Assuming a baseline of first-year scores, all QOL subscale scores were significantly improved except for QLQ-C30 global quality of life, QLQ-BR23 body image, and QLQ-BR23 future perception.For each time point, P < 0.01). After controlling for related variables, breast cancer surgery patients outperformed MRM patients in terms of role functioning, emotional functioning, cognitive functioning, body image and mental component summary, while TRAM patients outperformed BCS patients in terms of physical functioning, emotional functioning, sexual functioning, sexual enjoyment, physical component summary and mental component summary.P < 0.05). Conversely, patients who had received radiotherapy and hormone therapy generally had better QOL than patients who had not. In addition, patients with high preoperative QOL scores had high scores in all subscales for QLQ-C30, QLQ-BR23 and SF-36.Furthermore, in relatively older patients, QOL was statistically lower in those with the following characteristics: high CCI score, tumor stage III or IV, previous chemotherapy, and long post-operative LOS  and these improvements continued over the following 2 years. These results show that trends for each QOL subscale vary according to the complexity and the involvement of the lower extremities.Substantial differences were found among the cohorts in terms of age, CCI score, LOS, and tumor stage; however, the striking similarity of the data strongly supports the validity of the results. To examine longitudinal QOL trends, survey information was analyzed using the categorical time variable adjusted for patient and hospital characteristics. Regression model results reveal a significant performance improvement in each QOL subscale in the first 6 months following surgery  instead of item response theory (IRT) due to researchers being more familiar with CTT. While CTT uses observed scores that can be presumed to accurately represent “true” scores, IRT uses an underlying response model that relates the responses to a latent parameter. Therefore, further work is needed to assess the suitability of one or both methods in longitudinal questionnaire data analysis.The BCS group scored higher than the MRM group for role functioning, emotional functioning, cognitive functioning and body image but the TRAM group produced significantly larger subjective improvements in terms of physical functioning, emotional functioning, sexual functioning and sexual enjoyment. This may be due to the relatively younger age and earlier stages of the tumors of patients in this group.Age is also found to be an independent predictor of breast cancer surgery outcomes, reflecting findings that older patients experience greater improvements in QOL subscales than younger patients , 2. WhilMany co-morbidities are found to be linked with low QOL subscale scores, and previous reports have found that many co-morbidities are strongly associated with poor post-operative functional status , 13.Patients in the present study were found to have QLQ-BR23 scores for body image, sexual functioning, and future perspectives, comparable to the Dutch and American samples studied by Sprangers et al., but lower scores for sexual enjoyment . CompareA final interesting finding is that, over the 2-year period of the study, the single best predictor in each QOL subscale was preoperative health status, which is consistent with reports that the best predictors of postoperative outcomes are preoperative QOL scores. As this issue has been addressed elsewhere, data from a randomized trial comparing early and delayed breast cancer surgery would be of great value to clinicians when selecting the optimal timing of surgery. Therefore, effective counseling is essential for apprising patients of expected post-surgery impairments. If QOL outcomes are considered benchmarks, then accurately assessing preoperative functional status (a major predictor of postoperative outcome) is crucial.CSIS-BCP in a cloud environment enhances its flexibility, accessibility and usability [CSIS-BCP indeed enables researchers to integrate and analyze questionnaire data for breast-cancer patients easily and efficiently.Cloud computing technologies offer many advantages over conventional information technology infrastructure, including support for on-demand access to massive computational resources and massively reduced costs to the user. Therefore, implementing the sability –12, and CSIS-BCP, to solve privacy issues and to integrate diverse information from different stakeholders. For an improved interpretation of the data obtained in this study, eight post-interviews were performed at 1 year after the initial survey with the researchers, physicians, other caregivers, and patients. All interviewed participants agreed that the survey results provided insights into the successful use of a cloud-based technology that integrates the results of surveys of breast cancer surgery patients. However, the interviews also revealed that a major concern was that the user interface could not be customized for different types of users. Another issue raised was whether widespread adoption of the CSIS-BCP would be cost-effective. Therefore, further studies are needed to develop and evaluate the intangible value of the CSIS-BCP to provide a cloud-based service that is adaptable to changing researcher needs in the turbulent cancer research environment.Other objectives of this study were to clarify the actual requirements of the This is the first and a pilot study for designing a cloud-based system. We proposed to create the unique study environment in private cloud for the following reasons: First, the study data will be protected seriously under the ethical issues and regulations in Taiwan. Privacy concerns became the necessary consideration to protect the research data and respondents in the system development, such as referring the Health Information Technology for Economic and Clinical Health Act to secure electronic health information exchange or follow similar regulations in Taiwan. Second, informed consent forms for research studies now are required to include extensive detail on how the participant's protected health information will be kept private. Therefore, we build these mechanisms on the private cloud environment for on-premises and on-demand scalability. Base on previous discussions, we did not select the commercial cloud service  not only commercial product has security and information disclosure concerns, but also to consider the policy issues and related regulations with compliance in Taiwan. Furthermore, private cloud services allow this study more control over the cloud infrastructure, improving security and flexibility, because the user and the network are subject to special restrictions for maintaining privacy, and will not share personal information without express consent.We also provide research purpose and process in detail before the survey. Inform sense addressed and accepted respondent’s agreement, the system applied tokenization to provide a user id and password. For technical reasons, an encryption scheme usually uses a pseudo-random encryption key generated by an algorithm, and Tokenization applied to protect the privacy issues in this study. Hence, all symmetric cryptographic operations are based on AES-128 in our system. Generate privacy concerns when using an additional virtual server management, in order to avoid data theft. Although mega.co.nz similar commercial products can be used, but considering the application of the disclosure to commercial sites. Besides, commercial products are due to be attacked and to user and password-based private wastage have doubts. This study may refer the HIPAA proposed scheme in the future.Additionally, this study conducted the cost assessment that cloud-based compared to off-line (paper-based) methods. Generally, offline systems generally need to consider the additional expenditure like the previous comments discussion. Each respondent takes the traditional manner, the total costs than the cloud-based survey system is 4 to 5 times higher, and got the low response rate. The cloud-based system could provide the on-demand scalability and meet research requirements or scale in the future. In sum, this study found whether in tangible and intangible benefits, this system is superior to the traditional off-line method of investigation.Although all research questions were adequately and satisfactorily addressed, several limitations are noted. First, this study collected data from breast cancer surgery patients under the supervision of three surgeons in three different medical centers, each of whom had the highest surgeon volume in their respective hospitals. Such a sample selection procedure ensures that the limited experience of a surgeon does not significantly influence patient outcomes. By focusing the analysis on patients treated by these three orthopedists, the results of this study are thus more representative of all breast cancer surgery patients compared to one analyzing patients treated by a single surgeon. However, a notable limitation is that, in the prospective patient cohort, the first patient was enrolled in 2007. Therefore, depending on their inclusion date, some surveyed patients experienced longer follow-up than others, which may have caused selection bias. Nonetheless, subjects who remained in the study throughout the 2-year period and those who were lost to follow up between the 1st and 2nd years after discharge did not statistically differ in patient characteristics, hospital characteristics, or in any of the aforementioned preoperative QOL parameters (data not shown).Current trends in clinical medicine emphasize therapies and interventions to improve QOL, and patients more likely to benefit from interventions could potentially be identified through analyzing cloud-based QOL data. In addition to the surgical procedure, several other factors should be accounted for when evaluating post-operative QOL. Surgeons can use pre- and post-operative consultations to raise the awareness of breast cancer surgery candidates regarding the expected course of recovery and functional outcomes, and should to explain that pre-operative functional status has an important impact on postoperative QOL.


We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the  Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. At early stages of the disease only a small fraction of patients are amenable to curative treatments that include surgical resection, liver transplantation, or radiofrequency ablation . For pat in vitro makes them useful tools for therapeutic use in regenerative medicine, immunomodulation purposes and also as cellular carriers for therapeutic genes /[μW/cm2]. Signal present in tumor, liver, spleen, or lungs was expressed as percentage of total signal.Six- to eight-week-old male nude mice (Nu/Nu) were purchased from CNEA . Subcutaneous HuH7 tumors  and observed under a fluorescence microscope at 200x.t-test and one-way analysis of variance followed by posttests or Kruskal-Wallis and Dunn's posttests (GraphPad Prism Software) were used for statistical analyses. P values lower than 0.05 were considered as statistically significant.Unpaired 2-sided Student's  in vitro migration capacity of MSCs towards cell culture conditioned media (CCM) obtained from HCC cell lines (HuH7 and HC-PT-5), hepatic stellate cells (LX-2), fibroblasts (WI-38), and endothelial cells (HMEC-1). Interestingly, a higher migratory capacity towards all the CCM was found for HUCPVCs when compared to BM-MSCs  , surface BM-MSCs . Moreove BM-MSCs . in vivo, noninvasive migration assay was performed. CM-DiI and DiR prelabelled BM-MSCs or HUCPVCs were i.v. injected in HCC tumor-bearing mice in order to evaluate MSC recruitment. Similar to our previous observation with BM-MSCs [ in vitro migratory capacity towards TCM from HCC was observed for HUCPVCs when compared to BM-MSCs  8, GRO, chemokine (C-C motif) ligand (CCL)-2, and IL-6 are among the most relevant factors in HCC , we deci in vitro migration response to the recombinant AMF (rAMF) of both types of MSCs using a chemotaxis assay. A significantly higher migration to different doses of rAMF (0.5 and 0.75 μg/mL) was observed for HUCPVCs when compared to BM-MSCs , fibroblasts (WI-38), or tumor microendothelial cells (HMEC-1). Moreover, HUCPVCs also showed an enhanced adhesion capacity to HMEC-1 cells compared to BM-MSCs. This enhanced adhesion to endothelial cells could allow a more efficient arrest in tumor microvasculature which is a required step for MSC recruitment into HCC. In line with this, we observed that HUCPVCs also exhibited greater migration capacity in vivo towards experimental HCC. In contrast to that observed in the in vitro migration experiments, HUCPVCs showed a similar migration capability towards nontumoral tissues like liver or lung and also showed a lower recruitment to the spleen. Although HUCPVCs migrated better than BM-MSCs toward activated hepatic stellate cells in vitro, no differences were observed in in vivo migration to normal liver, where hepatic stellate cells are quiescent. In addition, it should be noted that mice injected with HUCPVCs showed a lower total signal than those injected with BM-MSCs, probably due to differences in the DiR uptake for both kinds of cells or in the number of inoculated cells. These results are in agreement with previous works showing that MCSs derived from umbilical cord are able to migrate towards experimental tumors such as glioma [The aim of this study was to assess the capability of different sources of MSCs to migrate towards HCC released factors in order to select those showing higher tumor recruitment capacity for future therapeutic applications. Our results indicated that although both types of MSCs share similar phenotypic characteristics as MSCs, HUCPVCs have a higher potential to migrates glioma , breast s glioma , and luns glioma . Nonethe in vitro and in vivo. Furthermore, other factors released by tumor stroma components like IL-8, GRO, IL-6, or CCL-2 could also be involved in MSC recruitment to HCC. Thus, differences observed between HUCPVCs and BM-MSCs in their in vitro and in vivo migration capacity towards HCC seem at least partially related to differences in the expression of cytokine/chemokine receptors. Some studies have screened for similarities or differences among BM-MSCs and UC-MSCs at the molecular level [ in vitro migration towards rAMF, but also the specific blockage of AMF in HC-PT-5 TCM was able to reduce HUCPVCs migration to a greater level when compared to BM-MSCs.Tumor-homing is thought to be mediated by interactions of cytokines/chemokines with their specific receptors. A number of cytokines, growth factors, and chemokines are secreted by HCC cells and their microenvironment . We havear level , 32. In ar level . In contar level , were ovar level , was fouar level . Finally in vivo [The potential use of MSCs in cancer treatment as carriers of therapeutic genes has raised some concerns about the safety of their use in the clinic. There are some studies that indicated that MSCs have protumorigenic capacity due to their immunosuppression properties, modulation of the epithelial-to-mesenchymal transition, and induction of angiogenesis . However in vivo . Moreove in vivo . In this in vivo  or even  in vitro but also in vivo, likely due to an increase in migratory response to AMF and to an enhanced adhesive capacity to tumor microvasculature. Considering their availability and that no invasive procedures are required to obtain HUCPVCs, these cells have advantages over BM-MSCs as candidates for carriers of therapeutic genes for the treatment of HCC.In summary, our results demonstrate a greater migration capacity to HCC of HUCPVCs when compared to BM-MSCs not only


The Global Physical Activity Questionnaire (GPAQ) was originally designed to be interviewer-administered by the World Health Organization in assessing physical activity. The main aim of this study was to compare the psychometric properties of a self-administered GPAQ with the original interviewer-administered approach. Additionally, this study explored whether using different accelerometry-based physical activity bout definitions might affect the questionnaire’s validity.A total of 110 participants were recruited and randomly allocated to an interviewer- (n = 56) or a self-administered (n = 54) group for test-retest reliability, of which 108 participants who met the wear time criteria were included in the validity study. Reliability was assessed by administration of questionnaires twice with a one-week interval. Criterion validity was assessed by comparing against seven-day accelerometer measures. Two definitions for accelerometry-data scoring were employed: (1) total-min of activity, and (2) 10-min bout.rs = 0.30) and interviewer-administration (rs = 0.46). Findings were similar when considering 10-min activity bouts in the accelerometer analysis for MVPA (rs = 0.29 vs. 0.42 for self vs. interviewer). Within each mode of administration, the strongest correlations were observed for vigorous-intensity activity. However, Bland-Altman plots illustrated bias toward overestimation for higher levels of MVPA, vigorous- and moderate-intensity activities, and underestimation for lower levels of these measures. Reliability for MVPA revealed moderate correlations (rs = 0.61 vs. 0.63 for self vs. interviewer).Participants had similar baseline characteristics in both administration groups and no significant difference was found between the two formats in terms of validity (correlations between the GPAQ and accelerometer). For validity, the GPAQ demonstrated fair-to-moderate correlations for moderate-to-vigorous physical activity (MVPA) for self-administration (Our findings showed comparability between both self- and interviewer-administration modes of the GPAQ. The GPAQ in general but especially the self-administered version may offer a relatively inexpensive method for measuring physical activity of various types and at different domains. However, there may be bias in the GPAQ measurements depending on the overall physical activity. It is advisable to incorporate accelerometers in future studies, particularly when measuring different intensities of physical activity. A continuous expanding body of literature shows that physical activity is amongst the most important determinants in the development of chronic diseases such as diabetes, stroke, hypertension, obesity, and coronary heart disease ,2. AlongQuestionnaires and objective tools (e.g. accelerometers and pedometers) are the most commonly used instruments in assessing physical activity. Of all the measuring methods, questionnaires are most widely used in large-scale epidemiological studies owing to their relatively low cost, minimal burden on participants and higher applicability of use . One of r = 0.31 to 0.54) and an accelerometer (r = 0.20 to 0.34), with reliability ranging from correlations of r = 0.39 to 0.81 ), and vigorous-intensity activity (>6167 CPM) . AccelerAccelerometry data were downloaded using ActiLife software (Version 6) and time spent in various physical activity levels (min/day) was assessed using the accelerometry package in R (Version 3.1.3).Descriptive sociodemographic characteristics, physical activity estimates, and categorization of participants into various physical activity levels were presented for all participants and separately for each mode of administration as median and interquartile range (IQR) or number (%). The differences in participants’ characteristics and accelerometry-based summary estimates of physical activity between the two modes of administration were assessed by a Fisher's exact test (if cells have an expected frequency of five or less) or a chi square test for categorical variables, and Mann-Whitney U test for continuous variables.Reliability and criterion validity of the GPAQ was assessed as follows:Test-retest reliability between the GPAQ for each mode of self- and interviewer-administration (min/day) at each activity intensity level  and by physical activity domains . Reliability testing was assessed using Spearman’s rank correlation test and the two-way mixed model (single measure) intraclass correlation coefficient (ICC) with 95% confidence interval (CI). ICCs were interpreted as follows: values below 0.40 are considered as poor agreement, 0.40–0.59 as moderate agreement, 0.60–0.79 as good agreement and ≥0.80 as excellent agreement . WeighteCriterion validity between the GPAQ at follow-up and accelerometry-derived data for each activity intensity level . The validity of each group was assessed using Spearman’s rank correlation test and Bland-Altman plots with the 95% limits of agreement (LOA). Bland-Altman plots were used to assess the agreement of physical activity at different activity intensities (min/day) between the GPAQ and accelerometer. To examine the variation of the Bland-Altman plots across different modes of administration, sensitivity analyses by self- and interviewer-administered groups were conducted.Thereafter, to assess if the Spearman correlations and Kappa values differed significantly between the self- and interviewer administered groups, a Z-test was used on the difference in the values ,23.All statistical procedures were performed using SPSS software  and Stata statistical software . Significance level was set at 0.05.A total of 110 participants were included in the test-retest reliability study, of which 108 participants who met the wear time criteria were included in the validity study. A flow chart of study participants’ recruitment is shown in rs = 0.61 and 0.63 for self- and interviewer-, respectively, p<0.001)  . Agreemers = 0.82 and 0.86, p<0.001; ICC: 0.70 and 0.76 for interviewer- and self-administered groups respectively). Moderate to strong correlations and agreement were observed for all domain-specific variables  for self-  and interviewer-administered group . Within the transport domain, there was a statistically significant difference in the Spearman’s coefficients between the two modes; in which the reliability coefficient in the interviewer-administered group was significantly higher than that of the self-administration . Nevertheless, within the same (transport) domain, a higher agreement was found in the self-administered group as compared to the interviewer- administered group .Among the activity domains, strongest correlations and agreement were presented for vigorous recreational activities for both groups . The highest correlation was apparent within recreational vigorous activity and total vigorous activity domains .Within all participants, the Spearman’s coefficients for the reliability of questionnaires were between moderate to excellent . There was no statistically significant difference when each kappa estimate was compared between the two groups.rs = 0.52, p<0.001) than it was among self-administered group , as well as when both groups were assessed together . There was moderate correlation between the GPAQ and accelerometer on MVPA min/day in self-administered group  and interviewer-administered group . In both administration groups combined, the GPAQ and accelerometer were moderately correlated with the accelerometer at moderate-intensity activity level  and MVPA level .In general, moderate correlations were found between the GPAQ at follow-up and accelerometry-derived estimates at all physical activity intensity levels . No signFindings were similar when considering 10-minute bouts of physical activity .Relative to the GPAQ, the Bland-Altman analyses revealed that the accelerometer measured lower daily total MVPA , vigorous-intensity activity  and moderate-intensity activity .When applying the 10-minute bout definition, Bland-Altman plots were similar. Lower accelerometry-derived physical activity was demonstrated as compared to the GPAQ  .The plots illustrate a bias towards overestimation of the MVPA with majority of the points falling above the zero line. The extent of overestimation of vigorous- and moderate-intensity activity level also increased with the duration of activities. Clear upward trends of measurement differences across the range of the measures were apparent in which the measurement differences became greater as the magnitude of reported time increased for each MVPA, vigorous- and moderate-intensity activity.None of the sensitivity analyses showed dissimilarity across self- and interviewer-administered groups, thus plots were constructed with both groups combined.To our knowledge, this is the first study to compare the psychometric properties of the GPAQ to measure physical activity between self- and interviewer-administered versions. An aim of this study was to evaluate the self-administered version of the GPAQ with the original interviewer-administered version among a population of literate adults who are fluent in English. The self-administered version performed similarly to the interviewer-administered version, and this would enhance its usability in assessing daily physical activities in population-based surveys by reducing questionnaire administrative burden. Our study presented fair-to-moderate criterion validity of the GPAQ via comparison with the accelerometry-measured physical activity, which is comparable between the two modes. These validity results are consistent with the findings reported by other researchers who validated the interviewer-administered GPAQ ,15,24. IOur study also demonstrates that relative to the GPAQ, the accelerometer provided up to almost one hour lower estimates of total MVPA per day, which agrees with earlier findings where an overestimation of self-reported MVPA was observed ,29. The Our findings are consistent with other research demonstrating stronger correlation in vigorous-intensity activities ,32. Thisr = 0.36 and r = 0.26, respectively). This seems to confirm the previously highlighted difficulties of accurately recalling moderate-to-vigorous intensity activities, especially activities accumulated in at least 10-minute bouts.The GPAQ, alongside with other commonly used physical activity questionnaires  were designed to collect physical activity information in accumulated bouts of at least 10-minute per session. Hence, this study considers the implications of using total minutes of activity and 10-minute bouts of activity to determine the accelerometry-derived activity measures. Based upon existing literature, it seems often unclear whether previous validation studies used total activity or 10-minute bouts for the direct comparison with self-report physical activity ,28. SeveApart from overestimation by self-report questionnaires, there are issues related to the use of accelerometers that can also contribute towards the discrepancy between both approaches and the observed moderate correlations. For instance, albeit being the most widely used objective tool to measure physical activity, accelerometers are known to underestimate certain activities . Activitrs = 0.61 vs. ICC: 0.28) of the reliability for total MVPA was not unexpected given participants in our study reported engaging more active transport activities and may hence influence the total level of MVPA. In contrast to these observations, the interviewer-administered mode has resulted in better test-retest reliability than self-administered mode in a study of elderly adults’ physical activity [Only few studies seem to have reported the reliability of the GPAQ . In our activity .Similar to our observations for validity, reliability was strongest for the assessment of vigorous recreational activities, which is consistent with previous studies ,46. ThisOur reliability result from the self-administration mode was comparable to Trinh et al.’s  in whichVariations in correlation coefficients and agreement of test-retest assessments were noted. Nonetheless, different measures suggested that all the GPAQ items provided acceptable reproducibility, which is consistent with results of Lachat et al.’s , which sReliability across all three domains was at least moderate, and the highest reliability was found for recreational activities. In line with our discussion of higher validity and reliability for vigorous intensity activities, this also seems to suggest that the relatively more structured and planned nature of recreational activities may be responsible for these results. However, our findings differ somewhat from those of Bull et al.  who repoThe strength of this study is the high compliance with accelerometer wear and adherence with the study protocol. Additionally, our study included a 24-hour accelerometer wear time protocol, which resulted in relatively high wearing durations per day. This might better reflect the physical activity pattern of a participant on a full day than the commonly used approach of focusing on waking time alone. Furthermore, participants were randomly assigned to two administration modes to avoid any potential bias for the comparison between groups. Through this random grouping method, the comparability between the two groups was achieved in relation to their sociodemographic characteristics.One of the limitations of our study is that the population of our study consisted of mostly full-time working adults and a small number of students from within the university and hospital workplace settings; thus, the results may have limited representativeness for the entire Singaporean population. Also, as the population studied comprised English-speaking adults with more than 50% of them having tertiary education; applicability to other populations cannot be assumed. Second, a bias in estimation of activity which is dependent on the duration of overall activities has been shown by the GPAQ, which introduces some errors. Nonetheless, previous studies have also presented similar findings, thus it is inevitable that the questionnaire are likely to be subject to performance limitations.In conclusion, this is among the first studies comparing the reliability and validity of the internationally widely used GPAQ considering two different modes of administration. Moreover, a 24-hour wear time protocol was employed and considered two different scenarios for accelerometer data processing. Our findings show that both interviewer- and self-administered modes of the GPAQ are comparable. Evidence for criterion validity was shown with fair-to-moderate correlation coefficients, of which the self-administration can be used in population-based studies.However, there was potential bias in estimation of activity differing at different intensities by the GPAQ. It should be noted that the pattern of over- and underestimation from the GPAQ is unpredictable; and these responses are dependent on the overall physical activity. Therefore, the use of GPAQ as a tool for investigation of adult physical activity patterns should be undertaken with caution.Future epidemiological studies could incorporate the GPAQ with a good understanding of various types and domains in which physical activity is carried out; together with objectively measured physical activity that provide a more accurate measure of overall activity levels and at various activity intensity levels.


Carbohydrate antigen 125 (CA-125), traditionally a tumor marker for screening, diagnosis, and monitoring in ovarian malignancy, had recently been shown increasing evidence and more extensively recognized/explored as a novel surrogate of heart failure (HF). The exact mechanisms underlying the pathophysiologic link between elevated serum CA-125 concentration and HF may be multi-factorial, with both mechanical and inflammatory process including numerous potential cytokines involved. Accumulating data had consistently indicated its diagnostic and prognostic role in HF patients in various clinical settings, however, there is limited clinical information regarding the incremental value or head-to-head comparison of such marker to other well-established HF markers. In this brief review, we aimed to discuss the biosynthesis, and potential insights of underlying pathophysiologies associated with CA-125 secretion in the scenarios of cardiac structural/functional alterations and HF, and further explored its current usage and roles in several recent reports. Carbohydrate antigen 125 (CA-125), also known as MUC16, is a glycoprotein belonging to the mucin (MUC) family .7. Another example is that elevation of CA-125 may happen in subjects with pleural effusion [Clinically CA-125 has long been used as a marker for ovarian cancer -6. In paeffusion . Based oSince CA-125 is expressed in epicardium, it is not surprising that cardiac disorders may be associated with elevated CA-125 levels in the blood. Nagele and associates firstly reported the findings of clinical or hemodynamical relevance of several tumor markers, with a special focus on CA-125, in patients with chronic heart failure before and after heart transplantation . Duman eSignificant elevation of CA125 level in a patient having atrial septal defect (ASD) with right ventricular dilatation was ever reported by Mathew et al. . The assInterpretation of elevated CA-125 levels in HF should consider the triggering factors as well as the production sites. These issues have been investigated and no simple answer was found. So far, production of CA-125 in subjects with HF had been hypothesized to happen with so-called “stressed” mesothelial cells, in response to both hemodynamic and inflammation stimuli . It had per se or other associated cytokines still remained a debate [On the other hand, the hypothetical link between pericardial stimuli and elevation of CA-125 in subjects with HF had also been observed. Seo et al.  ever repa debate . PerhapsThe range of value and potential clinical implication of CA-125 regarding its predictive value in monitoring HF beyond and the correlates with other well-established HF markers (e.g. BNP or NT-ProBNP) remained largely unknown. In general, serum CA-125 level seemed to be 7-fold higher  in subjects with acute HF, 2.5 times in chronic HF   and nearWith better understanding of the underlying biological mechanisms and pathophysiological processes of heart failure in the recent era, biomarker as a surrogate in disease screening, diagnosis, or as a guide to effects of therapy or outcomes had broadened the utilization of these tools by physicians in clinical settings. The incremental clinical value by using multi-biomarker panel looking into potentially diverse pathways or biological signaling involved in a clinical disease entity are evolving. CA-125, the glycoprotein primarily used for ovarian cancer screening or therapeutic monitoring, is gaining more and more attention as another role in heart failure. Insights into the understanding of its role and mechanisms involved in heart failure had made it different from other biomarkers for the same purpose, though questions and issues regarding the real determinants for such glycoprotein release, short- and long-term monitoring for treatment, and the potential costs as a routine marker for heart failure may worth further investigation.The authors declare that they have no competing interests.CLH drafted the manuscript. TCH and YHL had made substantial contributions to conceptual framework of this review. CSL had participated the graphing of CA125 molecular structure and figure edition. YJW involved in the drafting of the manuscript. HIY have given final approval of the version to be published. All authors read and approved the final manuscript.