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In this work, we present an air-permeable MXene electrode capable of recording surface electromyographic (sEMG) signals on the skin surface based on the Miura-ori structure. MXene is a two-dimensional (2D) nanomaterial composed of transition metal carbides, nitrides, and carbonitrides developed in recent years. Taking advantage of the Miura-ori structure, MXene-based electrodes have high breathability as well as low and stable electrode-skin interfacial impedances, facilitating long-term reliable electrophysiological monitoring. The electrolytic gel on conventional wet Ag/AgCl gel electrodes increases the impedance between the electrode and the skin as it gradually dries, inhibits sweat evaporation and affects signal acquisition. Therefore, we provide a fascinating electrode design that can be used to obtain high-quality sEMG signals for assessing body movements such as swallowing.

A new aerobic bacterial strain, designated strain YIM B02290

A Gram-stain-negative, aerobic, rod-shaped bacteria strain, named YIM B01951

A series of novel artemisinin-piperazine-phosphoramide mustard (PPM) hybrids were designed and synthesized by incorporating phosphoramide mustard (PM) into dihydroartemisinin (DHA) via an efficient, catalyst-free two-step sequential substitution. Artemisinin-PPM hybrids showed better cytotoxic potency against HepG2 cells than both the parent DHA and the reference, vincristine (VCR). Structure-activity relationship (SAR) studies showed that the cytotoxicity was significantly enhanced by the introduction of a thiazole moiety. Hybrid 7 h, the most potent compound with the highest selectivity index IC

Expression of cytokines and growth factors have been shown to be highly correlated with the prognosis of esophageal squamous cell carcinoma (ESCC), a deadly disease with poor prognosis. The suppressor of cytokine signaling (SOCS) family of proteins are key factors in regulating cytokines and growth factors. Yet the role of the SOCS proteins in ESCC is hardly investigated. We currently investigated the prognostic role of SOCS5 in ESCC. We analyzed the prognostic effects of 16 single nucleotide polymorphisms (SNPs) within the SOCS genes in 632 ESCC patients. We repeatedly observed that the 3 SNPs in SOCS5, SOCS5:rs3814039, SOCS5:rs3738890, and SOCS5: rs3768720, were significantly correlated with both overall (OS) and progression-free survival (PFS) of ESCC patients (rs3814039, p=0.032 for OS and p=0.009 for PFS; rs3738890, p=0.016 for OS, and p=0.008 for PFS; rs3768720, p=0.005 for OS and p=0.002 for PFS). SOCS5: rs3768720 was also significantly associated with distant metastasis (Ptrend=0.028). The luciferase assay revealed that SOCS5:rs3814039 and SOCS5: rs3768720 might influence the prognosis by regulating SOCS5 expression. Functional analysis demonstrated SOCS5 was able to regulate epidermal growth factor receptor (EGFR) expression and migration activity of ESCC cells. Furthermore, Patients with strong SOCS5 in normal tissues exhibited significantly better PFS (P=0.049) and reduced risk of distant metastasis (P=0.004) compared to those with weak SOCS5 expression. Overall, our study demonstrates the novel function of SOCS5 in ESCC prognosis. The genetic polymorphisms and expression of SOCS5 could serve as a novel therapeutic biomarker for improving the prognosis of ESCC.

Inexpensive and readily available calcium carbide (CaC2) has been developed as a promoter for the transition metal-free, solvent-free and one-pot conversion of acid chlorides and dimethyl sulfoxide (DMSO) to the corresponding β-keto sulfoxide. Four drug molecules were successfully converted to their β-keto sulfoxides using this method, emphasising its potential utility in medicinal chemistry.

OBJECTIVESWith the gradual acceptance of robotic-assisted surgery to treat oesophageal cancer and the application of a single-port approach in several abdominal procedures, we adopted a single-port technique in robotic-assisted minimally invasive oesophagectomy during the abdominal phase for gastric mobilization and abdominal lymph node dissection.METHODSRobotic-assisted oesophagectomy and mediastinal lymph node dissection in the chest were followed by robotic-assisted gastric mobilization and conduit creation with abdominal lymph node dissection, which were performed via a periumbilicus single incision. The oesophagogastrostomy was accomplished either in the chest (Ivor Lewis procedure) or neck (McKeown procedure) depending on the status of the proximal resection margin.RESULTSThe procedure was successfully performed on 11 patients with oesophageal cancer from January 2017 to December 2018 in our institute. No surgical or in-hospital deaths occurred, though we had one case each of anastomotic leakage, pneumonia and hiatal hernia (9%).CONCLUSIONSRobotic single-incision gastric mobilization for minimally invasive oesophagectomy for treating oesophageal cancer seems feasible. Its value in terms of perioperative outcome and long-term survival results awaits future evaluation.

The Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear.This study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro.The bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting.A total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment.QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-β-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.

Objective: In contrast to the drug situation in the rest of the world, synthetic drugs, rather than traditional drugs, have been the dominant abused drugs in China since 2019. However, the public misconception that synthetic drugs are not as addictive as traditional drugs, such as opioids and the scarcity of specific measurement instruments, have hindered the clinical diagnosis and treatment of synthetic drug abusers, thus the development of a localized instrument to evaluate dependence on synthetic drugs is in urgently needed.Method: Using a sample of 618 Chinese synthetic drug abusers (Mean age = 34.69 years; 44.17% female), the present study developed and examined the psychometric properties of a self-reporting instrument, the Synthetic Drug Dependence Scale (SDDS), which consists of four subscales: physical dependence, psychological dependence, health injury, and social function injury.Results: The SDDS revealed a three-factor model structure (weighted root mean square residual (WRMR) = 0.876, comparative fit index (CFI) = 0.965, Tucker–Lewis index (TLI) = 0.953, and Root mean square error of approximation (RMSEA) = 0.070), with good internal consistency (composite reliability = 0.912, alfa = 0.801) and convergent validity. Elevated scores on the SDDS were associated with a higher level of reward sensitivity, punishment sensitivity, and stronger impulsivity. Interestingly, psychological dependence was the only significant predictor (p < 0.05) of criterion variables compared with the other three subscales, implying the important role of psychological factors in synthetic drugs dependence. Adequate measurement equivalence across sex, age (18–30 and 31–57 years old), and employment group (employed and unemployed) was also established.Conclusion: The SDDS appears to be an effective and reliable instrument that could be used to further investigate the characteristics of synthetic and traditional drug dependence, promoting a deeper understanding of the physical and psychological roles in drug dependence.

As detriments in aquatic environments, microplastics (MPs) have been commonly studied on organisms, but tissue-scale effects of MPs were poorly understood. Discus fish (Symphysodon aequifasciatus), herewith, were exposed to polystyrene MPs (0/20/200 μg/L) for 28 d. We found that MPs significantly inhibited growth performance. MPs were observed in skin, gill and intestine after 14/28-d exposure. MPs bioaccumulation was independent of exposure time, but increased with MPs concentrations. Microbial community diversity of fish gill, but not skin and intestine, in MPs treatments was significantly increased. Bacterial community of MP-treated skin and gill were obviously separated from control. Skin dominant phyla changed from Actinobacteriota to Proteobacteria and Firmicutes. Proteobacteria gradually occupied dominance in gill after exposure. Furthermore, MPs-induced skin oxidative stress was demonstrated by the activation of superoxide dismutase and catalase. Skin malondialdehyde also increased and showed significant correlations with four bacterial phyla, e.g., Proteobacteria. Gill Na+/K+-ATPase activity decreased, strongly correlating to microbial community changes caused by MPs. Intestinal digestive enzymes activity (pepsin, lipase and α-amylase) reduced, revealing correlation with bacterial community especially Fibrobacterota. These results suggest a tissue-specific effect of MPs to microbial community and biomarkers in aquatic organism.

Methionine adenosyltransferases (MATs) synthesize S-adenosylmethionine (SAM) from methionine, which provides methyl groups for DNA, RNA, protein, and lipid methylation. MATs play a critical role in cellular processes, including growth, proliferation, and differentiation, and have been implicated in tumour development and progression. The expression of MATs is altered in hepatobiliary and pancreatic (HBP) cancers, which serves as a rare biomarker for early diagnosis and prognosis prediction of HBP cancers. Independent of SAM depletion in cells, MATs are often dysregulated at the transcriptional, post-transcriptional, and post-translational levels. Dysregulation of MATs is involved in carcinogenesis, chemotherapy resistance, T cell exhaustion, activation of tumour-associated macrophages, cancer stemness, and activation of tumourigenic pathways. Targeting MATs both directly and indirectly is a potential therapeutic strategy. This review summarizes the dysregulations of MATs, their proposed mechanism, diagnostic and prognostic roles, and potential therapeutic effects in context of HBP cancers.

Esophageal cancer is one of the leading causes of cancer death in the male population of Eastern Asia. In addition, esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer among the world. Owing to the poor overall 5-year survival rate, novel effective treatment strategies are needed. MicroRNAs are important gene regulators that are dysregulated in many cancer types. In our previous study, we applied next-generation sequencing to demonstrate that miR-338-5p was downregulated in the tumor tissue of patients with versus without recurrence. In this study, we further studied the roles of miR-338-5p in ESCC. The expression of endogenous miR-338-5p was at lower levels in ESCC cells compared with normal cells. Functional assays showed that miR-338-5p reduced cell proliferation, colony formation, migration and cisplatin resistance in an ESCC cell line, CE-81T. Potential target genes of miR-338-5p were identified by microarray and prediction tools, and 31 genes were selected. Among these, Fermitin family homolog 2 (FERMT2) plays an oncogenic role in ESCC, so it was chosen for further study. Luciferase assays showed the direct binding between miR-338-5p and the 3′ untranslated region of FERMT2. Silencing of FERMT2 inhibited cell proliferation, colony formation, migration and cisplatin resistance. Pathway analysis revealed that the integrin-linked protein kinase signaling pathway, in which FERMT2 participates, was significantly affected by a miR-338-5p mimic. Our results suggest that miR-338-5p may play an antioncogenic role in ESCC via repressing FERMT2.

For the first time, six novel artemisone–piperazine–tetronamide hybrids (12a–f) were efficiently synthesised from dihydroartemisinin (DHA) and investigated for their in vitro cytotoxicity against some human cancer cells and benign cells. All the targets showed good cytotoxic activity in vitro. Hybrid 12a exhibited much better inhibitory activity against human liver cancer cell line SMMC-7721 (IC50 = 0.03 ± 0.04 μM for 24 h) than the parent DHA (IC50 > 0.7 μM), and two references, vincristine (VCR; IC50 = 0.27 ± 0.03 μM) & cytosine arabinoside (ARA; IC50 = 0.63 ± 0.04 μM). Furthermore, hybrid 12a had low toxicity against human benign liver cell line LO2 (IC50 = 0.70 ± 0.02 μM for 24 h) compared with VCR, ARA, and DHA in vitro. Moreover, the inhibitory activity of hybrid 12a was obviously enhanced when human liver cancer cell line MHCC97H absorbed Fe2+ in vitro.

Background/purpose: For high risk of central line-associated bloodstream infections (CLABSIs) in patients of intensive care units (ICUs) and scarcely epidemiology and therapeutic recommendations in Asia, we aimed to evaluate the annual change in epidemiology, antibiogram, and risk factors for 14-day mortality. Methods: A retrospective study of ICUs patients with CLABSIs at a medical center in Taiwan (2010–2016), where central line care bundle implemented since 2014, by reviewing clinical data, pathogens, and the antibiogram. Results: Gram-negative bacteria (59.3%) were main microorganisms of CLABSIs, and 9.0% of all GNB were MDROs. Acinetobacter spp., Enterobacter spp., and Stenotrophomonas maltophilia were the most frequently isolated. In multivariate analysis, malignancy, inadequate empirical antimicrobial therapy, inadequate definite antimicrobial therapy, and infection by fungi or multidrug-resistant organisms (MDROs) were associated with 14-day mortality (all p

KH-type splicing regulatory protein (KSRP) is a single-strand RNA binding protein which regulates mRNA stability either by binding to AU-rich elements (AREs) of mRNA 3'UTR or by facilitating miRNA biogenesis to target mRNA. Unlike its well-characterized function at the molecular level in maintaining RNA homeostasis, the role of KSRP in cancer progression remains largely unknown. Here we investigate the role of KSRP in non-small cell lung cancer (NSCLC). We first examined KSRP expression by immunohistochemistry in a cohort containing 196 NSCLC patients and observed a strong positive correlation between KSRP expression and survival of NSCLC patients. Multivariate analysis further identified KSRP as an independent prognostic factor. Manipulating KSRP expression significantly affected in vitro cell mobility and in vivo metastatic ability of NSCLC cells. Microarray analysis identified an ARE-containing gene, EGR3, as a downstream effector of KSRP in NSCLC. Interestingly, we found that KSRP decreased EGR3 mRNA stability in an ARE-independent manner. By screening KSRP-regulated miRNAs in NSCLC cells, we further found that miR-23a directly binds to EGR3 3'UTR, reducing EGR3 expression and thereby inhibiting NSCLC cell mobility. Our findings implicate a targetable KSRP/miR-23a/EGR3 signaling axis in advanced tumor phenotypes.

// Pei-Wen Yang 1, * , Min-Shu Hsieh 2, 3, * , Ya-Han Chang 1 , Pei-Ming Huang 1 and Jang-Ming Lee 1 1 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 3 Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Jang-Ming Lee, email: jmlee@ntu.edu.tw Keywords: esophageal squamous cell carcinoma (ESCC), ATG5, SNP, recurrence Received: June 20, 2017 Accepted: July 27, 2017 Published: September 08, 2017 ABSTRACT Esophageal squamous cell carcinoma (ESCC) is a deadly disease with high risk of tumor recurrence even among patients with an early pathologic stage of tumor. In the current study, we investigate the association between 20 SNPs of the ATG5 gene and prognosis of patients with early-stage ESCC. A total of 305 patients diagnosed with early-stage ESCC were enrolled in the study and randomly assigned to a training set (n=93) or replication set (n=212). The genotypes of candidate SNPs (single nucleotide polymorphisms) within ATG5 were analyzed and correlated with the prognosis of ESCC patients. We repeatedly demonstrated that 3 SNPs in ATG5, rs1322178, rs3804329, and rs671116, were significantly correlated with the prognosis of patients with early-stage ESCC (HR[95 % CI]=2.01[1.19-3.40], p=0.009 for ATG5: rs1322178; HR[95 % CI]=1.88 [1.08-3.26], p=0.025 for ATG5:rs3804329; HR[95 % CI]=1.73[1.24-2.42], p=0.001 for ATG5:rs671116, in combined group). Both rs1322178 and rs3804329 can predict early distant metastasis of patients. Furthermore, increased expression of ATG5 was observed in ESCC tumor tissue as compared to adjacent normal tissue. Moreover, higher levels of ATG5 expression in both normal and tumor tissues exhibited a trend to correlate with poor prognosis of patients. However, the expression of ATG5 did not correlate with these 3 relevant prognostic SNPs. We concluded that hereditary genetic polymorphisms and gene expression of ATG5 can serve as prognostic predictors of patients with early-stage ESCC.

Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors. Transforming growth factor-betas (TGF-βs) and their most specific signal transduction factors, Smads, are expressed in the endometrium during the window of implantation. Recent researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo implantation. In this study, we measured the expression of TGF-β1, TGF-β receptor type I (TβRI), Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4, 5 and 6 of pseudopregnancy. Then we administrated a specific Smad3 inhibitor (Sis3) into the uterine cavity of mice on day 3 of pregnancy. The results showed a reduction in insulin-like growth factor-1 (IGFBP-1) expression and the decreased number of implanted embryo after the administration. In addition, Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells. Taken all together, our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.

For the first time, eight novel artemisinin-piperazine-furane ether hybrids (5a−h) were efficiently synthesized and investigated for their in vitro cytotoxic activity against some human cancer and benign cells. The absolute configuration of hybrid 5c was determined by X-ray crystallographic analysis. Hybrids 5a−h exhibited more pronounced growth-inhibiting action on hepatocarcinoma cell lines than their parent dihydroartemisinin (DHA) and the reference cytosine arabinoside (ARA). The hybrid 5a showed the best cytotoxic activity against human hepatocarcinoma cells SMMC-7721 (IC50 = 0.26 ± 0.03 μM) after 24 h. Furthermore, hybrid 5a also showed good cytotoxic activity against human breast cancer cells MCF-7 and low cytotoxicity against human breast benign cells MCF-10A in vitro. We found the cytotoxicity of hybrid 5a did not change when tumour cells absorb iron sulfate (FeSO4); thus, we conclude the anti-tumour mechanism induced by iron ions (Fe2+) is unclear.

To compare the perioperative outcome of minimally invasive (MIE) esophagectomy performed with a single- or a multi-incision in treating esophageal cancer. Patients with esophageal cancer who underwent MIE from 2006 to 2016 were evaluated. A 3–4-cm incision was created in both the thoracoscopic and the laparoscopic phases during the single-incision MIE procedures. A propensity-matched comparison was made between the two groups of patients. We analyzed a total of 48 pairs of patients with propensity-matched from the cohort of 360 patients undergoing MIE during 2006–2015. There is no statistical difference in terms of postoperative ICU and hospital stay, number of dissected lymph nodes and presence of major surgical complications (anastomotic leakage and pulmonary complications) between the two groups of patients. The pain score one week after surgery was significantly lower in the single-incision group (p

Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P

Hiatal hernia after minimally invasive esophagectomy (MIE) is an important postoperative complication that can cause severe morbidity or even mortality among patients with esophageal cancer. Usually repair of the hiatus immediately after esophageal reconstruction is suggested to prevent such complication. However, during the Ivor Lewis MIE procedure, hiatal repair is difficult to perform due to the deep-seated location of the hiatus after the final step of esophageal reconstruction in the right chest. The current study demonstrates a method of repairing the hiatus in the Ivor Lewis MIE. This is especially useful in the resection of a massive tumor near the esophagogastric (E-G) junction, which harbors a high risk of hiatal hernia when the hiatus is left unrepaired after extensive hiatal dissection.

Secondary mutation of epidermal growth factor receptor (EGFR) resulting in drug resistance is one of the most critical issues in lung cancer therapy. Several drugs are being developed to overcome EGFR tyrosine kinase inhibitor (TKI) resistance. Here, we report that pyruvate kinase M2 (PKM2) stabilized mutant EGFR protein by direct interaction and sustained cell survival signaling in lung cancer cells. PKM2 silencing resulted in markedly reduced mutant EGFR expression in TKI-sensitive or -resistant human lung cancer cells, and in inhibition of tumor growth in their xenografts, concomitant with downregulation of EGFR-related signaling. Mechanistically, PKM2 directly interacted with mutant EGFR and heat-shock protein 90 (HSP90), and thus stabilized EGFR by maintaining its binding with HSP90 and co-chaperones. Stabilization of EGFR relied on dimeric PKM2, and the protein half-life of mutant EGFR decreased when PKM2 was forced into its tetramer form. Clinical levels of PKM2 positively correlated with mutant EGFR expression and with patient outcome. These results reveal a previously undescribed non-glycolysis function of PKM2 in the cytoplasm, which contribute to EGFR-dependent tumorigenesis and provide a novel strategy to overcome drug resistance to EGFR TKIs.

Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.

No effective targeted therapy exists for esophageal squamous cell carcinoma (ESCC), the major cell type of esophageal cancer. The pleiotropic cytokine interleukin (IL)-6 is associated with adverse prognosis of some cancers, and the open reading frame of IL-6 contains an miR-608 microRNA-targeted site. We investigated the correlation of circulating IL-6 levels with prognosis and with the mir608:rs4919510 genetic polymorphism in ESCC. A total of 213 patients with primary ESCC were enrolled. Plasma IL-6 levels of ESCC patients were analyzed by enzyme-linked immunosorbent assay (ELISA). The patients’ genotypes of mir608:rs4919510 were analyzed using the MassARRAY system, and functional assays were performed by transient overexpression in cells. The cytotoxicity of IL-6 signaling blockers in ESCC cells was analyzed by MTT assay. We found that plasma IL-6 levels significantly correlated with overall survival (p = 0.019), disease recurrence (p = 0.003), and postoperative complications (p =0.002). Patients with the GG genotype of mir608:rs4919510 had a 4.56-fold increased risk of high expression of IL-6 compared with patients with the CC genotype (odds ratio 4.56, 95% confidence interval 1.87–11.09; p =0.001). Transient overexpression of the miR-608 C (miR-608_C) and G variants (miR-608_G) in cancer cells revealed that the miR-608_G variant was less efficient in regulating the expression of IL-6 compared with miR-608_C. Finally, the IL-6 signaling blocker ruxolitinib exhibited effective cytotoxicity in ESCC cells. The results of this study provide a novel direction for a biomarker-based targeted therapy for ESCC.

Objective: To observe the developmental dynamics of Trichinella spiralis in the host. Methods: Ten female Kunming mice were involved in the experiments, each of which was infected with 100 Trichinella spiralis larvae. Two mice were respectively killed after the infection of 60 days, 120 days, 180 days, 300 days and 400 days. The cysts of Trichinella spiralis were detected with staining method. Results: After the infection of 60 days, the capsules were fully mature; 120 days later, inner layer began to appear transparent and inner layer were completely transparent up to 400 days. Conclusion: The longer the infection time, the fuller the capsule developed, that it is, the development trend was the shape from the spindle to the ovoid to the circular, and the inner layer of transparency gradually increased.

Epstein-Barr virus (EBV) BKRF3 shares sequence homology with members of the uracil-N-glycosylase (UNG) protein family and has DNA glycosylase activity. Here, we explored how BKRF3 participates in the DNA replication complex and contributes to viral DNA replication. Exogenously expressed Flag-BKRF3 was distributed mostly in the cytoplasm, whereas BKRF3 was translocated into the nucleus and colocalized with the EBV DNA polymerase BALF5 in the replication compartment during EBV lytic replication. The expression level of BKRF3 increased gradually during viral replication, coupled with a decrease of cellular UNG2, suggesting BKRF3 enzyme activity compensates for UNG2 and ensures the fidelity of viral DNA replication. In immunoprecipitation-Western blotting, BKRF3 was coimmunoprecipitated with BALF5, the polymerase processivity factor BMRF1, and the immediate-early transactivator Rta. Coexpression of BMRF1 appeared to facilitate the nuclear targeting of BKRF3 in immunofluorescence staining. Residues 164 to 255 of BKRF3 were required for interaction with Rta and BALF5, whereas residues 81 to 166 of BKRF3 were critical for BMRF1 interaction in glutathione S -transferase (GST) pulldown experiments. Viral DNA replication was defective in cells harboring BKRF3 knockout EBV bacmids. In complementation assays, the catalytic mutant BKRF3(Q90L,D91N) restored viral DNA replication, whereas the leucine loop mutant BKRF3(H213L) only partially rescued viral DNA replication, coupled with a reduced ability to interact with the viral DNA polymerase and Rta. Our data suggest that BKRF3 plays a critical role in viral DNA synthesis predominantly through its interactions with viral proteins in the DNA replication compartment, while its enzymatic activity may be supplementary for uracil DNA glycosylase (UDG) function during virus replication. IMPORTANCE Catalytic activities of both cellular UDG UNG2 and viral UDGs contribute to herpesviral DNA replication. To ensure that the enzyme activity executes at the right time and the right place in DNA replication forks, complex formation with other components in the DNA replication machinery provides an important regulation for UDG function. In this study, we provide the mechanism for EBV UDG BKRF3 nuclear targeting and the interacting domains of BKRF3 with viral DNA replication proteins. Through knockout and complementation approaches, we further demonstrate that in addition to UDG activity, the interaction of BKRF3 with viral proteins in the replication compartment is crucial for efficient viral DNA replication.

With the growing evidence of clinical benefit of minimally invasive esophagectomy (MIE) combined video-assisted thoracoscopic surgery (VATS) and laparoscopy procedures, we describe how these procedures can be performed with single-incision both in the abdominal and thoracic phases. Clinical observation of the midterm results has demonstrated its feasibility and benefit of relieving postoperative pain. However, the long-term impact on the survival of the patients requires to be evaluated in the future.

Thoracic surgeons should be more aware of the latest information about histopathological, genetic and epigenetic alterations that may influence treatment policy and patient outcome in the biomolecular era. Translational research studies often produce a promising diagnostic tool or new treatment that can be used clinically. The results of these translational studies may even change the practical guidelines and current staging system in thoracic malignancies. The following article summarizes the experiences of translational research in esophageal cancer and non-small cell lung cancer (NSCLC) at National Taiwan University Hospital in Taiwan.

Purpose To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors ( i.e ., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62–10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57–10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.