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An I2-mediated aerobic cyclization reaction of anilines, alkynes, and tertiary amine has been reported. In this protocol, a novel strategy for the synthesis of quinolines using tertiary amines as a C1 synthon via C–N bond cleavage.

A palladium-catalyzed dearomatizing [2+2+1] spiroannulation of indoles with two molecular internal alkynes is developed in the presence of Cu(OAc)

Fatty acid synthase (FASN), a sole cytosolic enzyme responsible for de-novo lipid synthesis, is overexpressed in cancer but not in normal non-lipogenic tissues. FASN has been targeted, albeit no such inhibitor has been approved. Proton pump inhibitors (PPIs), approved for digestive disorders, were found to inhibit FASN with anticancer activities in attempting to repurpose Food and Drug Administration-approved drugs. Indeed, PPI usage benefited breast cancer patients and increased their response rate. Due to structural similarity, we thought that their metabolites might extend anticancer effects of PPIs by inhibiting FASN. Here, we tested this hypothesis and found that 5-hydroxy lansoprazole sulfide (5HLS), the end lansoprazole metabolite, was more active than lansoprazole in inhibiting FASN function and regulation of NHEJ repair of oxidative DNA damage via PARP1. Surprisingly, 5HLS inhibits the enoyl reductase, whereas lansoprazole inhibits the thioesterase of FASN. Thus, PPI metabolites may contribute to the lasting anticancer effects of PPIs by inhibiting FASN.

Many oncoproteins are considered undruggable because they lack enzymatic activities. In this study, we present a small-molecule–based anticancer agent that acts by inhibiting dimerization of the oncoprotein survivin, thereby promoting its degradation along with spontaneous apoptosis in cancer cells. Through a combination of computational analysis of the dimerization interface and in silico screening, we identified one compound that induced proteasome-dependent survivin degradation. Analysis of a set of structural analogues led us to identify a lead compound (LQZ-7F), which was effective in blocking the survival of multiple cancer cell lines in a low micromolar concentration range. LQZ-7F induced proteasome-dependent survivin degradation, mitotic arrest, and apoptosis, and it blocked the growth of human tumors in mouse xenograft assays. In addition to providing preclinical proof of concept for a survivin-targeting anticancer agent, our work offers novel in silico screening strategies to therapeutically target homodimeric oncogenic proteins considered undruggable. Cancer Res; 76(2); 453–62. ©2016 AACR.

Effect of compounds from in-silico screening on cancer cell survival.

Molecular-based dielectric switching compounds [ClEt-Dabco][ReO4]2 and [BrEt-Dabco][ReO4]2 with high-temperature phase transition.

Here, we report a series of organic–inorganic hybrid halide materials, with rare and fully reversible thermochromism, narrow bandgaps, and near-infrared luminescence. Thermochromism induced bandgap narrowing provide new insights for the further of organic–inorganic hybrid materials.

Switchable dielectric materials are attracting tremendous interest due to their low cost of manufacture, environment protection and structural flexibility. However, most of them have a single function. Here, we report one switchable dielectric material with high phase transition temperature based on 4-Ethylmorpholine. [4-Ethylmorpholine]2MnCl4 with the phase transition temperature of 425 K. What is more interesting is that this compound also has photoluminescence characteristic. Owing to the excellent switchable dielectric transition and efficacious Photoluminescence, this work may extend the application of switchable dielectric materials in the field of luminescence and multifunctional devices.

Four organic–inorganic hybrid materials were designed, and a successful adjustment of the band gap was obtained, from 2.933 eV to as low as 2.788 eV, via replacing the third hydrogen atom of the benzene ring in the organic cation with a halogen.

Human fatty acid synthase (FASN) is the sole cytosolic enzyme responsible for de novo lipid synthesis. FASN is essential for cancer cell survival and contributes to drug and radiation resistance by up-regulating DNA damage repair but not required for most non-lipogenic tissues. Thus, FASN is an attractive target for drug discovery. However, despite decades of effort in targeting FASN, no FASN inhibitors have been approved due to poor pharmacokinetics or toxicities. Here, we show that the FDA-approved proton pump inhibitors (PPIs) effectively inhibit FASN and suppress breast cancer cell survival. PPI inhibition of FASN leads to suppression of non-homologous end joining repair of DNA damages by reducing FASN-mediated PARP1 expression, resulting in apoptosis from oxidative DNA damages and sensitization of cellular resistance to doxorubicin and ionizing radiation. Mining electronic medical records of 6754 breast cancer patients showed that PPI usage significantly increased overall survival and reduced disease recurrence of these patients. Hence, PPIs may be repurposed as anticancer drugs for breast cancer treatments by targeting FASN to overcome drug and radiation resistance.

With 12 representative states such as Ohio and Illinois as examples, the disciplinary system for acupuncturists in the United States is introduced. The disciplinary system mainly covers several aspects such as the subject of the implementation, the types of illegal acts, the form of disciplinary responsibility, and the hearing procedure. The acupuncture industry association has the responsibility of disciplinary action in most states. Corresponding disciplinary measures will be taken depending on the illegal activities of acupuncturists according to the types of illegal practice specified by each state. The hearing procedure provides procedural guarantee for the subsequent rights protection activities of acupuncturists.以有代表性的美国俄亥俄州、伊利诺伊州等12州为例，介绍相对成熟的美国针灸师惩戒制度。惩戒制度主要涵盖实施主体、违法行为种类、责任形式和听证程序等内容。美国大多数州由针灸行业协会组织承担惩戒职能，在惩戒程序启动后，依据各州针灸法案规定的针灸师违法行为类型，视其具体违法情形采取相应的处罚措施。听证程序为针灸师后续的维权活动提供程序保障。.

This is a cross-sectional study that compares the sales of “healthy” and “unhealthy” vending machines following the introduction of healthier vending machines on a university campus. Method: Health...

Survivin, a member of the inhibitor of apoptosis protein family, exists as a homodimer and is aberrantly upregulated in a wide spectrum of cancers. It was thought to be an ideal target due to its lack of expression in most adult normal tissues and importance in cancer cell survival. However, it has been challenging to target survivin due to its “undruggable” nature. We previously attempted to target its dimerization domain with a hypothesis that inhibiting survivin dimerization would promote its degradation in proteasome, which led to identification of a lead small-molecule inhibitor, LQZ-7F. LQZ-7F consists of a flat tetracyclic aromatic core with labile hydrazone linking a 1,2,5-oxadiazole moiety. In this study, we tested the hypothesis that LQZ-7F could be developed as a prodrug because the labile hydrazone linker could be hydrolyzed, releasing the tetracyclic aromatic core. To this end, we synthesized the tetracyclic aromatic core (LQZ-7F1) using reported procedure and tested LQZ-7F1 for its biological activities. Here we show that LQZ-7F1 has a significantly improved potency with submicromolar IC(50’s) and induces spontaneous apoptosis in prostate cancer cells. It also more effectively inhibits survivin dimerization and induces survivin degradation in a proteasome-dependent manner than LQZ-7F. We also show that the combination of LQZ-7F1 and docetaxel have strong synergism in inhibiting prostate cancer cell survival. Together, we conclude that the hydrazone linker with the oxadiazole tail is dispensable for survivin inhibition and the survivin dimerization inhibitor, LQZ-7F, may be developed as a prodrug for prostate cancer treatment and to overcome docetaxel resistance.

Due to the low-grade glioma (LGG) infiltrative nature, it can be challenging to cure patients suffering from this condition only with surgery or multi-drug adjuvant chemotherapy. LGG patients usually have poor prognoses, making the exploration in therapeutic tools and accurate prognosis that are different from traditional ones a novel topic in the medical field. In recent years, the regulation of ceRNA networks in the tumor microenvironment (TME) by immune cell infiltration has generated a research boom, providing new perspectives for tumor treatment and predicting patient prognosis. However, the role of the ceRNA network in regulating the LGG tumor microenvironment is not effectively understood yet. In this study, we obtained LGG patient data with complete survival information from the TCGA database and constructed a novel immune infiltration pattern-related ceRNA regulatory network and a novel prognostic model, which was multi-dimensionally validated to have better predictive features in terms of LGG prognosis. Our study reveals the potential association and clinical significance of the ceRNA network with immune infiltration and survival prediction of these patients.

Eukaryotic translation initiation factor 3 subunit A (eIF3a), the largest subunit of the eIF3 complex, has been shown to be overexpressed in malignant cancer cells, potentially making it a proto-oncogene. eIF3a overexpression can drive cancer cell proliferation but contributes to better prognosis. While its contribution to prognosis was previously shown to be due to its function in suppressing synthesis of DNA damage repair proteins, it remains unclear how eIF3a regulates cancer cell proliferation. In this study, we show using genetic approaches that eIF3a controls cell proliferation by regulating glucose metabolism via the phosphorylation and activation of AMP-activated protein kinase alpha (AMPKα) at Thr

BackgroundAcute kidney injury (AKI) is a common complication of sepsis and is an independent risk factor for mortality. It is unclear whether different bacteria play different roles in the occurrence and development of sepsis-associated AKI (S-AKI). We observed the clinical characteristics and outcomes of patients that have types of bacterial infection, and different infections sites before the occurrence of AKI, respectively.MethodsData of patients who were diagnosed with sepsis and later developed AKI from 2008 to 2019 were retrieved from the MIMIC-IV 1.0 database. Patients were first divided into the two groups according to the bacterial culture results obtained prior to AKI occurrence: bacterial cultured positive (N = 1,785) and bacterial cultured negative (N = 8,777). Patients with bacteria culture positive were divided into culture bacteria Gram-positive (CGP, N = 1248) and Gram-negative (CGN, N = 537) groups.ResultsOverall, 1,785 patients were included in the present analysis. The patients in CGN group were older (70 vs. 66, p < 0.001), had lower body mass index (BMI) (27.0 vs. 28.4, p < 0.001), higher acute physiology III (APS III) score (63.0 vs. 58, p = 0.001), shorter time from positive microbial culture to diagnosis of AKI (2.94 vs. 3.16 days, p = 0.013) and longer intensive care unit (ICU) stay time (5.94 vs. 4.77 days, p < 0.001) compared with those in the CGP group (n = 1,248). In the culture gram-negative bacteria in patients with positive blood cultures (CGNb) group, the rate of vasopressors using (73.1 vs. 56.4%, P = 0.007), the Sequential Organ Failure Assessment (SOFA) score (10 vs. 9, p = 0.005), and the level of lactate (3.7 vs. 2.5, p = 0.001) were higher than those in the culture gram-positive bacteria in patients with positive blood cultures (CGPb) group. The time from positive microbial culture to the diagnosis of AKI was shorter (2.23 vs. 3 days, p = 0.001) in the CGNb group. However, there was no significant difference in the continuous renal replacement treatment (CRRT) application or short-term mortality rates between CGN and CGP groups.ConclusionThe Gram types of bacteria cultured prior to S-AKI occurrence was not related to AKI stage, CRRT application, and short-term mortality. Compared with the Gram-positive bacterial infections, Gram-negative bacterial infections take a shorter time to develop into AKI, and had a higher disease severity score.

In order to stabilize the output fluctuation of wind power generation, this paper applies control strategy to control the action of the battery energy storage system according to the stability target, and quickly makes up for the system demand. In this paper, the optimal scheduling of new energy power system with energy storage is studied. This model predictive control is introduced into a certain system and optimized by model predictive control strategy so that the combination can match the predetermined expectations. Then, the model predictive control strategy is used to improve the schedulability of the wind farm. The objective function is to minimize the amount of action, and the composite output can track the scheduling instructions. Considering the cost, the way of storage and operation cost is optimized, and the penalty cost of wind abandonment is also reduced. Through rolling optimization and feedback correction, the model predictive control is optimized and solved, and finally, the action instructions of the storage system are obtained so that the storage output can effectively calm the wind. Power makes the combination schedulable. The optimized wind power/energy storage output is equivalent to the benign and dispatchable power supply of the power grid.

The argyrodite Ag

eIF3a (eukaryotic translation initiation factor 3a), a subunit of the eIF3 complex, has been suggested to play a regulatory role in protein synthesis and in cellular response to DNA-damaging treatments. S6K1 is an effector and a mediator of mTOR complex 1 (mTORC1) in regulating protein synthesis and integrating diverse signals into control of cell growth and response to stress. Here, we show that eIF3a regulates S6K1 activity by inhibiting mTORC1 kinase via regulating Raptor synthesis. The regulation of Raptor synthesis is via eIF3a interaction with HuR (human antigen R) and binding of the eIF3a-HuR complex to the 5'-UTR of Raptor mRNA. Furthermore, mTORC1 may mediate eIF3a function in cellular response to cisplatin by regulating synthesis of NER proteins and NER activity. Taken together, we conclude that the mTOR signaling pathway may also be regulated by translational control and mediate eIF3a regulation of cancer cell response to cisplatin by regulating NER protein synthesis.

A series of ultrafiltration (UF) membranes based on mixed matrix of chromium-doped strontium titanate (SrTiO3–Cr) photocatalyst and polyvinylidene difluoride (PVDF) were systematically prepared by non-solvent induced phase inversion technique. Porous PVDF membrane and mixed matrix membranes (MMMs) incorporated with 3–10 wt% SrTiO3–Cr were produced in the UF range using polyethylene glycol as a porogen additive. The crystal morphology and electronic property of as-synthesized Cr-doped SrTiO3 nanoparticles were characterized by XRD and UV–Vis DRS. We found that the SrTiO3–Cr nanoparticles are cubic perovskite structure of approximately 30–40 nm in size with a low band gap energy of 2.05 eV. The morphology, surface roughness, hydrophilicity and textural properties of SrTiO3–Cr/PVDF MMMs were comprehensively characterized using field emission-scanning electron microscope with energy-dispersive X-ray spectroscopy, atomic force microscope, sessile drop technique, and capillary flow porometer. The SrTiO3–Cr was observed to be homogeneously dispersed in all the MMMs and provided additional anti-fouling properties from Bovine Serum Albumin (BSA) protein. The membrane UF property and tri-cycling performance were evaluated under three distinct protocols in (1) Dark, (2) constant UVA exposure, and (3) UVA during post-treatment clean only. By increasing the SrTiO3–Cr concentration, the MMMs displayed an improved homogeneity and macropore distribution with enhanced water permeability given by 51–110 LMH bar−1 pure water flux and 37 to 45 LMH bar−1 BSA water flux in the Dark. A consistently high BSA rejection of 95% and an improved anti-fouling property under constant UVA irradiation were achieved due to a combination of photo-induced hydrophilic and photocatalytic effect. Also, a significant improvement in UF performance in terms of membrane flux recovery was observed in the 3rd protocol signifying that the effect of protein fouling on membrane filtration was further reduced due to a lower degree of BSA fragment deposition in the membrane pores. The findings in this study dramatically lower the operational constraints (transmembrane pressure, membrane cleaning, use of UVA) in the protein filtration process and offer an innovative membrane material for the research of photo-induced, anti-fouling membranes for protein separation applications.

IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Flow cytometry was performed to identify the cell origin of IL-26. The effects of tuberculosis-specific antigen (ESAT-6/CFP-10) on IL-26 expression of CD4+ T cell were explored. The impacts of IL-26 on modulating CD4+ T cell polarization were also investigated. The concentrations of IL-26 were much higher in tuberculous, malignant, and infectious PE than those in the corresponding serum. The expression of IL-26 on CD4+ T cells was much higher in tuberculous PE than those in the corresponding serum, and pleural Th1 and Th17 cells might be the major cell sources of IL-26. The addition of ESAT-6/CFP-10 to CD4+ T cells led to increasing the number of IL-26-producing CD4+ T cells and IL-26 expression on Th1 and Th17 cells. IL-26 could induce the differentiation and generation of IL-22 by memory and naive CD4+ T cells. IL-26 also upregulated the mRNA encoding CC-chemokine ligand 20 (CCL20) and CCL22 by mononuclear cells isolated from TPE. This study implies that pleural Th1 and Th17 cells are the major cell sources of IL-26, which could induce the differentiation and generation of Th22 cells by CD4+ T cells, suggesting the involvement of IL-26 in the pathogenesis of human TPE. KEY MESSAGES: IL-26 is overexpressed in TPE patients and presents a higher concentration in pleural effusion than the corresponding peripheral blood. Pleural Th1 and Th17 cells might be the major cell sources of IL-26 in TPE patients. IL-26 promotes IL-22 secretion and Th22 generation by CD4+ T cells isolated from TPE patients. IL-26 may play an active role in the pathogenesis of tuberculous pleurisy.

Purpose: Fatty acid synthase (FASN) is overexpressed in 70% of operable triple-negative breast cancer (TNBC) and is associated with poor prognosis. Proton pump inhibitors selectively inhibit FASN activity and induce apoptosis in TNBC cell lines. Patients and Methods: Patients with operable TNBC were enrolled in this single-arm phase II study. Patients began omeprazole 80 mg orally twice daily for 4–7 days prior to neoadjuvant anthracycline–taxane-based chemotherapy (AC-T) and continued until surgery. The primary endpoint was pathologic complete response (pCR) in patients with baseline FASN overexpression (FASN+). Secondary endpoints included pCR in all surgery patients, change in FASN expression, enzyme activity, and downstream protein expression after omeprazole monotherapy, safety, and limited omeprazole pharmacokinetics. Results: Forty-two patients were recruited with a median age of 51 years (28–72). Most patients had ≥cT2 (33, 79%) and ≥N1 (22, 52%) disease. FASN overexpression prior to AC-T was identified in 29 of 34 (85%) evaluable samples. The pCR rate was 72.4% [95% confidence interval (CI), 52.8–87.3] in FASN+ patients and 74.4% (95% CI, 57.9–87.0) in all surgery patients. Peak omeprazole concentration was significantly higher than the IC50 for FASN inhibition observed in preclinical testing; FASN expression significantly decreased with omeprazole monotherapy [mean change 0.12 (SD, 0.25); P = 0.02]. Omeprazole was well tolerated with no grade ≥ 3 toxicities. Conclusions: FASN is commonly expressed in early TNBC. Omeprazole can be safely administered in doses that inhibit FASN. The addition of omeprazole to neoadjuvant AC-T yields a promising pCR rate that needs further confirmation in randomized studies.

eIF3i, a 36-kDa protein, is a putative subunit of the eIF3 complex important for translation initiation of mRNAs. It is a WD40 domain-containing protein with seven WD40 repeats that forms a β-propeller structure with an important function in pre-initiation complex formation and mRNA translation initiation. In addition to participating in the eIF3 complex formation for global translational control, eIF3i may bind to specific mRNAs and regulate their translation individually. Furthermore, eIF3i has been shown to bind to TGF-β type II receptor and participate in TGF-β signaling. It may also participate in and regulate other signaling pathways including Wnt/β-catenin pathway via translational regulation of COX-2 synthesis. These multiple canonical and noncanonical functions of eIF3i in translational control and in regulating signal transduction pathways may be responsible for its role in cell differentiation, cell cycle regulation, proliferation, and tumorigenesis. In this review, we will critically evaluate recent progresses and assess future prospects in studying eIF3i.

Translation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide excision repair. In this study, we tested the hypothesis that eIF3a regulates the synthesis of proteins important for the repair of double-strand DNA breaks induced by ionizing radiation (IR). We found that eIF3a upregulation sensitized cellular response to IR while its downregulation caused resistance to IR. eIF3a increases IR-induced DNA damages and decreases non-homologous end joining (NHEJ) activity by suppressing the synthesis of NHEJ repair proteins. Furthermore, analysis of existing patient database shows that eIF3a expression associates with better overall survival of breast, gastric, lung, and ovarian cancer patients. These findings together suggest that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating the synthesis of DNA repair proteins and, thus, eIIF3a likely contributes to the outcome of cancer patients treated with DNA-damaging strategies including IR.

Survivin, a homodimeric member of the Inhibitor of Apoptosis Protein (IAP) family, is required for cancer cell survival and overexpressed in almost all solid tumors. However, targeting survivin has been challenging due to its "undruggable" nature. Recently, we used a novel approach to target the dimerization interface and identified inhibitors of two scaffolds that can directly bind to and inhibit survivin dimerization. One of the scaffolds, represented by the compound LQZ-7, contains an undesirable labile hydrazone linker and a potentially nonfunctional furazanopyrazine ring that we attempted to eliminate in this study. We found one compound, 7I, that is more active than the parent compound, LQZ-7, and when given orally effectively inhibits xenograft tumor growth and induces survivin loss in tumors. These findings indicate that 7I with a stable linker and a quinoxaline ring can be used as a lead for further optimization of this novel class of survivin inhibitors.

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and plays important roles in multiple aspects of cancer aggressiveness. Thus, targeting STAT3 promises to be an attractive strategy for the treatment of advanced metastatic tumors. Bisindolylmaleimide alkaloid (BMA) has been shown to have anti-cancer activities and was thought to suppress tumor cell growth by inhibiting protein kinase C. In this study, we show that a newly synthesized BMA analog, BMA097, is effective in suppressing tumor cell and xenograft growth and in inducing spontaneous apoptosis. We also provide evidence that BMA097 binds directly to the SH2 domain of STAT3 and inhibits STAT3 phosphorylation and activation, leading to reduced expression of STAT3 downstream target genes. Structure activity relationship analysis revealed that the hydroxymethyl group in the 2,5-dihydropyrrole-2,5-dione prohibits STAT3 inhibitory activity of BMA analogs. Altogether, we conclude that the synthetic BMA analogs may be developed as anti-cancer drugs by targeting and binding to the SH2 domain of STAT3 and inhibiting the STAT3 signaling pathway.

ConspectusMaterials that can directly convert electricity into heat, i.e., thermoelectric materials, have attracted renewed attention globally for sustainable energy applications. As one of the state-of-the-art thermoelectric materials, In4Se3 features an interesting crystal structure of quasi-two-dimensional sheets comprising In/Se chains that provide a platform to achieve a Peierls distortion and support a charge density wave instability. Single-crystal In4Se3−δ (δ = 0.65) shows strong anisotropy in its thermoelectric properties with a very high ZT of 1.48 at 705 K in the b–c plane (one of the highest values for an n-type thermoelectric material to date) but a much lower ZT of approximately 0.5 in the a–b plane. Because of the random dispersion of grains and the grain boundary effect, the electrical transport properties of polycrystalline In4Se3 are poor, which is the main impediment to improve their performance. The In4-site in the In4Se3 unit cell is substitutional for dopants such as Pb, which increa...

Dispersive optics quantum key distribution (DO-QKD) based on energy-time entangled photon pairs is an important QKD scheme. In DO-QKD, the arrival time of photons is used in key generation and security analysis, which would be greatly affected by fiber dispersion. In this work, we established a theoretical model of the entanglement-based DO-QKD system, considering the protocol, physical processes (such as fiber transmission and single-photon detection), and the analysis of security tests. Based on this theoretical model, we investigate the influence of chromatic dispersion introduced by transmission fibers on the performance of DO-QKD. By analyzing the benefits and costs of dispersion compensation, the system performance under G.652 and G.655 optical fibers are shown, respectively. The results show that dispersion compensation is unnecessary for DO-QKD systems in campus networks and even metro networks. Whereas, it is still required in DO-QKD systems with longer fiber transmission distances.

Background The utility of tumor markers (TMs) for differentiating malignant pleural effusion (MPE) from benign pleural effusion (BPE) has been a subject of controversy. The majority of published studies are single center designed and lack validation. We performed a derivation and validation study in China to evaluate the diagnostic value of carcinoembryonic antigen (CEA) as well as carbohydrate antigen (CA) 15-3, CA 19-9 and CA 125 to differentiate between MPE and BPE. Methods Three hundred and twenty seven pleural effusion (PE) and paired serum samples were collected from consecutive patients with MPE or BPE in Beijing (174 patients, derivation) and Wuhan (153 patients, validation) during the same period. The concentrations of four TMs were tested using chemiluminescent microparticle immunoassay technology. The performance of the TMs was analyzed by standard receiver operating characteristic (ROC) curves. Results The levels of four TMs were significantly higher in MPE than in BPE and the corresponding serum. The concentrations of CEA and CA 15-3 were more stable than the concentrations of CA 125 and CA 19-9. CEA was the best single marker for discriminating MPE from BPE. With a specificity of 100% in the total population, the highest sensitivity (37.8%) using serum was found in CEA. In addition, CEA presented 19.8% sensitivity in PE and 18.0% sensitivity in the Δ(PE-serum). For CA 15-3, the sensitivity was 32.4% in PE, 15.3% in the PE/serum ratio and 25.2% in the Δ(PE-serum). Conclusions CEA and CA 15-3 rather than CA 125 and CA 19-9 are more reliable to differentiate between MPE and BPE. The use of the Δ(PE-serum) value in TMs, such as CEA and CA 15-3, may improve the sensitivity and specificity of the diagnosis etiology of PE.