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Introduction Postoperative pain after thoracic surgery impairs patients’ quality of life and increases the incidence of respiratory complications. Optimised analgesia strategies include minimally invasive incisions, regional analgesia and early chest tube removal. However, little is known about the optimal analgesic regimen for uniportal video-assisted thoracoscopic surgery (uVATS).Methods and analysis We will conduct a single-centre, prospective, single-blind, randomised trial. The effects of postoperative analgesia will be tested using thoracic paravertebral block (PVB) in combination with patient-controlled intravenous analgesia (PVB+PCIA), erector spinae plane block (ESPB) in combination with patient-controlled intravenous analgesia (ESPB+PCIA) or PCIA alone; 102 patients undergoing uVATS will be enrolled in this study. Patients will be randomly assigned to the PVB group (30 mL of 0.33% ropivacaine with dexamethasone), ESPB group (40 mL of 0.25% ropivacaine with dexamethasone) or control groups. PCIA with sufentanil will be administered to all patients after surgery. The primary outcome will be total opioid consumption after surgery. Secondary outcomes include postoperative pain score; postoperative chronic pain at rest and during coughing; sensations of touch and pain in the chest wall, non-opioid analgesic consumption; length of stay; ambulation time, the total cost of hospitalisation and long-term postoperative analgesia. Adverse reactions to analgesics and adverse events related to the regional blocks will also be recorded. The statisticians will be blinded to the group allocation. Comparison of the continuous data among the three groups will be performed using a one-way analysis of variance to assess differences among the means.Ethics and dissemination The results will be published in patient education courses, academic conferences and peer-reviewed journals.Trial registration number NCT06016777.

Introduction Postoperative laryngopharyngeal discomfort after extubation can lead to severe throat pain, dysphagia, or postoperative tongue oedema. Possible mechanisms include increased oral pressure, obstruction of venous and lymphatic return in the neck, and increased capillary hydrostatic pressure, which leads to oedema of the tongue and upper airway. However, real-time monitoring indicators of anaesthesia are lacking. Therefore, we designed this study to accurately measure the contact force of the tracheal tube on the tongue in different surgical positions during general anaesthesia.Methods and analysis This prospective single-centre observational study will enrol 54 patients undergoing elective surgery under general anaesthesia for>2 hours with endotracheal tube application from 1 July 2023 to 30 June 2024. Patients will be divided into the supine (Supine group) and high-risk (Flexion group) groups. Dynamic changes in the contact force between the tracheal tube and tongue will be measured using T-Scan technology. All patients will be followed up for 7 days postoperatively. The primary endpoint is postoperative laryngopharyngeal discomfort. Secondary outcomes include the time to the first successful recovery of oral intake of fluids and solid food, and airway-related events.Ethics and dissemination Ethical approval was obtained from the Ethics Committee of Clinical Research of China-Japan Friendship Hospital (2023-KY-219, approved on 14 September 2023). Informed consent will be obtained during anaesthesia evaluation. This study aims to explore the characteristics of the contact force on the tongue caused by endotracheal intubation in different surgical positions and to provide a better understanding of the risk factors and prevention of postoperative laryngopharyngeal discomfort. The findings of this study will be presented at our hospital, reported on ClinicalTrials.gov, and published in peer-reviewed journals.Trial registration number NCT05987293.

Canola expeller (CE) contains ~200 g/kg residual oil, but also fiber that impairs nutrient digestibility in weaned pigs. To study if feed enzymes increase digestibility, six diets containing either the basal or two CE samples mixed in at 250 g/kg (CE-A or CE-B) were formulated with or without a multi-enzyme blend containing cellulase, xylanase, glucanase, amylase, protease, invertase, and pectinase. The basal diet containing 620 g/kg wheat and 150 g/kg barley served as control. Twelve ileal-cannulated barrows (9–15 kg) were fed the six diets in a replicated 6 (pigs) × 3 (periods) Youden square. Ileal digestibility of gross energy and amino acids was 5% greater for basal than CE diets without differences between CE samples. Diet energy values were 4% greater for CE than basal diets due to residual oil in CE. Inclusion of the multi-enzyme blend increased total tract digestibility of energy of the basal but not CE diets by 2%. Net energy value was greater for CE-A than CE-B because CE-A contained more residual oil. In conclusion, feeding 250 g/kg CE increased diet energy values; thus, CE can substitute added fat in weaned pig diets. Feeding the multi-enzyme blend increased the energy digestibility of wheat and barley-based diets fed to weaned pigs. However, research is needed to identify enzyme combinations that increase the nutrient digestibility of CE.

In order to improve the added value of walnut, walnut glutelin peptides (WGPs), which were prepared from walnut meal, were chelated with zinc ions. The zinc chelating characteristics of WGPs were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) spectroscopy. The peptides were screened for zinc binding capacity by ultrafiltration, gel column chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the specific binding sites and binding capacity of the peptides were explored by molecular docking. The results showed that WGPs could chelate with zinc ions, leading to significant alterations in the surface microstructure and crystallinity of the peptides. After ultrafiltration and gel column chromatography, fraction F41, which had the highest chelating capacity of (117.43 ± 1.99) mg/g, was obtained. By LC-MS/MS combined with virtual screening, five potential bioactive peptides without toxicity or allergenic potential were identified. Molecular docking was used to simulate and analyze the binding process. It was found that pentapeptide Phe-Asp-Ala-Asp-Phe (FDADF) could form a structurally stable complex with zinc ions through coordination bonds, hydrogen bonds and hydrophobic interactions. Among the five peptides, the pentapeptide exhibited the lowest binding energy (−7.27 kcal/mol), and the main binding site was the carboxyl oxygen atom (Asp4:O-Zn) of the aspartic acid (Asp) side chain. This study provides a theoretical basis for the development and application of zinc-chelating peptides.

Abstract Background The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high‐dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. Methods We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real‐world setting. Patients were divided into three groups according to induction regimens. Results The median age of the cohort was 70 (65–86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow‐up of the cohort was 30 (interquartile range [IQR] 18–36) months. For the entire cohort median progression‐free survival (PFS) was 26 (IQR 12.00–42.89) months and overall survival (OS) was 60 (IQR 40.00–67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy

Abstract Background Vibrio scophthalmi is an opportunistic bacterial pathogen, which is widely distributed in the marine environment. Earlier studies have suggested that it is a normal microorganism in the turbot gut. However, recent studies have confirmed that this bacterial strain can cause diseases in many different marine animals. Therefore, it is necessary to investigate its whole genome for better understanding its physiological and pathogenic mechanisms. Results In the present study, we obtained a pathogenic strain of V. scophthalmi from diseased half-smooth tongue sole (Cynoglossus semilaevis) and sequenced its whole genome. Its genome contained two circular chromosomes and two plasmids with a total size of 3,541,838 bp, which harbored 3185 coding genes. Among these genes, 2648, 2298, and 1915 genes could be found through annotation information in COG, Blast2GO, and KEGG databases, respectively. Moreover, 10 genomic islands were predicted to exist in the chromosome I through IslandViewer online system. Comparison analysis in VFDB and PHI databases showed that this strain had 334 potential virulence-related genes and 518 pathogen-host interaction-related genes. Although it contained genes related to four secretion systems of T1SS, T2SS, T4SS, and T6SS, there was only one complete T2SS secretion system. Based on CARD database blast results, 180 drug resistance genes belonging to 27 antibiotic resistance categories were found in the whole genome of such strain. However, there were many differences between the phenotype and genotype of drug resistance. Conclusions Based on the whole genome analysis, the pathogenic V. scophthalmi strain contained many types of genes related to pathogenicity and drug resistance. Moreover, it showed inconsistency between phenotype and genotype on drug resistance. These results suggested that the physiological mechanism seemed to be complex.

Background/purpose: Rituximab is effective in treating pemphigus both as the first-line treatment and as an add-on treatment for refractory disease. A high rate of relapse among patients receiving rituximab means that maintenance therapy is frequently required. Therefore, we aimed to evaluate the use of azathioprine as maintenance therapy for patients receiving rituximab and to investigate the efficacy and safety of one or multiple cycles of rituximab treatment. Methods: We retrospectively collected data regarding pemphigus patients treated with rituximab from 2008 to 2015 with at least one year of follow-up at a referral center in Northern Taiwan. The medical records and clinical data were reviewed to determine the efficacy and complication rate of the treatment. Results: A total of 78 pemphigus patients were identified. Ninety-one percent of the patients achieved complete remission after the first cycle of rituximab with a relapse rate of 67.9%. Repeated cycles of rituximab showed a trend to shorten the time to next complete remission and to reduce the rate of subsequent relapses. The adverse events were usually not severe and were manageable. Use of azathioprine significantly prolonged the duration of remission (21.98 ± 16.24 vs. 9.98 ± 7.93 months, P = 0.0232). This effect of azathioprine usage remained after univariate and multivariate logistic regressions. Conclusion: This study provides an insight that azathioprine could serve as a good choice of maintenance therapy for patients receiving rituximab. The efficacy and safety of rituximab remain favorable even with repeated administration. Keywords: Azathioprine, Maintenance, Pemphigus, Rituximab

Lung ischemia-reperfusion (IR) injury is induced by pulmonary artery occlusion and reperfusion. Lung IR injury commonly happens after weaning from extracorporeal circulation, lung transplantation, and pulmonary thromboendarterectomy; it is a lethal perioperative complication. A definite therapeutic intervention remains to be determined. It is known that the enzyme activity of angiotensin-converting enzyme 2 (ACE2) is critical in maintaining pulmonary vascular tone and epithelial integrity. In a noxious environment to the lungs, inactivation of ACE2 is mainly due to a disintegrin and metalloprotease 17 (ADAM17) protein-mediated ACE2 shedding. Thus, we assumed that protection of local ACE2 in the lung against ADAM17-mediated shedding would be a therapeutic target for lung IR injury. In this study, we established both in vivo and in vitro models to demonstrate that the damage degree of lung IR injury depends on the loss of ACE2 and ACE2 enzyme dysfunction in lung tissue. Treatment with ACE2 protectant diminazen aceturate (DIZE) maintained higher ACE2 enzyme activity and reduced angiotensin II, angiotensin type 1 receptor, and ADAM17 levels in the lung tissue. Concurrently, DIZE-inhibited oxidative stress and nitrosative stress via p38MAPK and NF-κB pathways consequently reduced release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. The underlying molecular mechanism of DIZE contributed to its protective effect against lung IR injury and resulted in the improvement of oxygenation index and ameliorating pulmonary pathological damage. We concluded that DIZE protects the lungs from IR injury via inhibition of ADAM17-mediated ACE2 shedding.

Paclitaxel (PTX) is a widely used chemotherapy drug; however, frequent use causes multidrug resistance (MDR), which limits the utility of PTX against advanced non-small-cell lung cancer (NSCLC). PTX-resistant subline (NCI-H23-TXR) was established in vitro by exposing NCI-H23 cells to gradually increased concentrations of PTX in culture medium. Distinct Beclin expression of autophagy level was observed between resistant NCI-H23-TXR and parental NCI-H23 cells. Beclin-small interfering RNA (siRNA) was selected to restore sensitivity of PTX against NCI-H23-TXR. Chondroitin sulfate-polyethylenimine (CS-PEI) was constructed for delivery and protection of Beclin-siRNA. To delineate the underlying molecular mechanism of Beclin knockdown, we analyzed different MDR expression proteins of two cells using western blot, and the corresponding genes were confirmed by real-time PCR. Compared with NCI-H23, NCI-H23-TXR had higher expression levels in P-glycoprotein (P-gp) and multidrug resistance protein 7 (ABCC10). Knockdown of Beclin simultaneously inhibited P-gp and ABCC10, and renewed the sensitivity of PTX against NCI-H23-TXR. Research on zebrafish embryos revealed that tumor sizes decreased in NCI-H23 tumor xenografts but remained intact in NCI-H23-TXR tumor xenografts as zebrafish were treated with 1 μg/mL PTX. In contrast, the tumor sizes decreased in NCI-H23-TXR tumor xenografts with zebrafish pre-transfected with CS-PEI/Beclin-siRNA followed by the same treatment of PTX. The role of autophagy was associated with MDR development. This study paves the way for a new avenue of PTX in MDR-related lung cancer therapy using CS-PEI as a gene delivery carrier. Keywords: autophagy, Beclin-siRNA, multidrug resistance, MDR, non-viral gene delivery vector, paclitaxel, PTX

The therapeutic modalities for glioblastoma multiforme fail badly due to the limitations of poor penetration through the blood–brain barrier and the lack of tumor targeting. In this study, we synthesized a neuropeptide (ANGIOPEP-2)-functionalized gold nanorod (GNR-ANGI-2) and systemically evaluated the cellular uptake and photothermal effects enhanced by the neuropeptide functionalization of the gold nanorod under laser or sham exposure. The expression of LRP1, the specific ligand for ANGIOPEP-2, was the highest in C6 cells among five studied glioma cell lines. The cellular internalization studies showed higher uptake of gold nanorods functionalized with ANGIOPEP-2 than of those functionalized with scrambled ANGIOPEP-2. The in vitro photothermal studies of C6 cells treated with GNR-ANGI-2 and laser showed a higher rate of apoptosis at early and late stages than cells treated with GNR-ANGI-2 without laser. Correspondingly, in vitro ROS evaluation showed a higher intensity of ROS production in cells treated with GNR-ANGI-2 under laser irradiation. The Western blotting results indicated that GNR-ANGI-2 with laser exposure activated the caspase pathway of apoptosis, and GNR-ANGI-2 with sham exposure induced autophagy in C6 cells. The current study provides in-depth knowledge on the effective time point for maximum cellular uptake of GNR-ANGI-2 to achieve a better anti-glioma effect. Moreover, by exploring the molecular mechanism of cell death with GNR-ANGI-2-mediated photothermal therapy, we could modify the nanoshuttle with multimodal targets to achieve more efficient anti-glioma therapy in the future.

Angiogenesis is the process of vascular network development and plays a crucial role in cancer growth, progression, and metastasis. Phthalates are a class of environmental pollutants that have detrimental effects on human health and are reported to increase cancer risk. However, the interplay between phthalate exposure and angiogenesis has not been investigated thoroughly. In this study, we investigated the effect of prolonged di (2-ethylhexyl) phthalate (DEHP) treatment on the angiogenic potential of triple-negative breast cancer. MDA-MB-231 cells were exposed to physiological concentrations of DEHP for more than three months. Prolonged DEHP exposure induced angiogenesis in breast cancer cells. Endoglin (ENG)/CD105 is a membrane glycoprotein and an auxiliary receptor of the TGFβ receptor complex. In endothelial cells, ENG is highly expressed and it is a prerequisite for developmental angiogenesis. A literature review highlights endoglin as a well-known mesenchymal stem cell marker responsible for vascular development and angiogenesis. NGS analysis showed that endoglin overexpression in DEHP-exposed MDA-MB-231 cells correlated with tumor development and growth. An in vivo zebrafish xenograft assay showed that VEGFA induced sprouting of the subintestinal vein (SIV) in embryos injected with DEHP-exposed cells. Endoglin knockdown reduced SIV sprouting and VEGFA expression in zebrafish embryos. An in vitro HUVEC tube formation assay showed that endoglin depletion reversed DEHP-induced VEGF-mediated HUVEC tube formation in coculture. DEHP-induced endoglin activated TGFβ/SMAD3/VEGF and MAPK/p38 signaling in MDA-MB-231 cells. A cytokine angiogenesis antibody array showed induced expression of the inflammatory cytokines IL1α, IL1β, IL6, and IL8, along with GMCSF and VEGF. Endoglin knockdown reversed DEHP-induced activation of the TGFβ/SMAD3/VEGF signaling axis, MAPK/p38 signaling, and cytokine regulation, limiting angiogenesis potential both in vivo and in vitro. Targeting endoglin might serve as a potential alternative treatment to control angiogenesis, leading to metastasis and limiting cancer progression.

Abstract Background Schistosomiasis was severely prevalent in Yunnan Province, and it is difficult to achieve its elimination by convention approaches due to complexity of the nature. We explored the comprehensive model to eliminate schistosomiasis in Eryuan County, Yunnan Province, the People’s Republic of China, through integration with the ecological protection programme in Erhai Lake, in order to promote an efficient elimination strategy. We expected that this model is able to be tailored to other local settings, which help achieve the goal of precisely eliminating the disease in Yunnan Province. Methods Eryuan County of Yunnan Province was chosen as the study area, where the data on environmental protection activities in Erhai Lake and on the schistosomiasis control programme were collected through different departments of Erhai County government since 2015. System modelling was performed using system dynamics software to establish a simulation model in order to evaluate the effectiveness of intervention activities. Results Ecological approaches to control schistosomiasis in Eryuan County consist of three major components: (i) implementing precise interventions to stop schistosomiasis transmission by means of controlling the source of infection, blocking the biological transmission chains and cutting off the route of disease transmission; (ii) employing ecological approaches to improve the co-effectiveness of environmental protection and schistosomiasis prevention in the study area; and (iii) strengthening the professional skills of personnel involving in the schistosomiasis control programme. Simulation results showed that this strategy could speed up the progress of schistosomiasis control programme moving from the control stage to the elimination stage. Conclusions Ecological approaches implemented in schistosomiasis endemic areas of the Eryuan region are able to improve the co-effectiveness of environmental protection and schistosomiasis control, providing a new avenue for eliminating schistosomiasis thanks to the application of precise interventions.

Background: Arterial grafts had better mid-term and long-term patency than saphenous vein grafts in coronary artery bypass grafting (CABG). We summarized our experience with total arterial off-pump coronary artery bypass grafting (OPCAB) and assessed the early clinical results, surgical complications, and follow-up. Methods: From January 2007 to May 2017, 508 coronary artery disease patients undergoing total arterial OPCAB were enrolled. Clinical features, approaches, outcomes of surgical treatments, and follow-up data of these patients were studied retrospectively. A total of 122 patients underwent single left internal mammary artery (IMA)-left anterior descending artery grafts, whereas the other 386 patients underwent multiple vessel grafts. Results: The average distal anastomosis was 2.34 ± 0.97 (range: 1–4). All the patients were discharged from hospital except one died. A total of 457 (90.32%) patients were followed up. In the 4-, 7-, and 10-year follow-up groups, the rate of death from any cause was 1.19%, 6.47%, and 10.67%; rate of cardiac death was 0.60%, 2.88%, and 3.33%; rate of repeat revascularization was 0.00%, 3.60%, and 8.67%; rate of ischemic symptoms was 1.79%, 7.91%, and 11.33%; and incidence of stroke was 2.38%, 4.32%, and 6.67%, respectively. Poor medication adherence was observed in 9.38% of the follow-up population. Conclusions: Total arterial OPCAB with bilateral IMA, radial artery, and right gastroepiploic artery grafting yielded satisfactory early and midterm outcomes in this patient group, without a significant increase in early mortality or morbidity. Moreover, the long-term outcomes are also positive.

Abstract Background Quick diagnosis of smear-negative pulmonary tuberculosis (TB) and extra-pulmonary TB are urgently needed in clinical diagnosis. Our research aims to investigate the usefulness of the interferon-γ release assay (IGRA) for the diagnosis of smear-negative pulmonary and extra-pulmonary TB. Methods We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients (including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients), 113 extra-pulmonary TB patients, 81 patients with other pulmonary diseases and 100 healthy controls. Blood samples for the TB-Ab test and the TB-IGRA were collected, processed, and interpreted according to the manufacturer’s protocol. Results The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8% (109 of 120) and 89.6% (241 of 269), respectively. There was no statistically significant difference of its performance between these two sample sets (P > 0.05). The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0% (350 of 389) and 87.6% (99 of 113), respectively, which was not significantly different (P > 0.05). Conclusions In this work, the total detection ratio using TB-IGRA was 89.4%, therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.

Background: Effective management of psoriasis is a cause for much concern. In Taiwan, there is a lack of consensus on management strategies for psoriasis, especially the principles of drug prescribing in psoriatic patients. Objectives: The Taiwanese Dermatological Association convened Expert Panel meetings three times between 2012 and 2015 to discuss the management strategies for treatment of psoriasis in order to fill the knowledge gap and provide a reference tool for Taiwanese dermatologists. Results: This paper reports the final output from the three meetings, with the aim of aiding clinical decision making in terms of principles of prescribing, including dosing strategies, efficacy profiles, and safety concerns in connection with eight categories of antipsoriatic treatment: topical agents, phototherapy, nonbiologic conventional systemic agents, licensed biologic systemic agents, newly emerging therapies, combination therapy, transitional therapy, and traditional Chinese medicine. Conclusion: The Expert Panel, comprising distinguished Taiwanese dermatologists, succeeded in developing a consensus about the management of psoriasis in Taiwanese patients. Unavailability of data in certain areas may suggest a possibility of new directions in research.

Background/Aims: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. Methods: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay. Results: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3β. GSK-3 inhibitor and GSK-3β siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation. Conclusion: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3β activation was involved in bufalin-induced apoptosis.

The characteristics of phthalates had been thought to be similar to endocrine disruptors, which increases cancer risk. The role of phthalates in acquired drug resistance remains unclear. In this study, we investigated the effect of di-(2-ethylhexyl) phthalate (DEHP) on acquired drug resistance in breast cancer. MCF7 and MDA-MB-231 breast cancer cells were exposed to long-term physiological concentration of DEHP for more than three months. Long-exposure DEHP permanently attenuated the anti-proliferative effect of doxorubicin with estrogen receptor-independent activity even after withdrawal of DEHP. Long term DEHP exposure significantly reduced ROS (O2−) level in MDA-MB-231 cells while increased in MCF7 cells. ATP-binding cassette (ABC) transporters possess a widely recognized mechanism of drug resistance and are considered a target for drug therapy. Upregulation of ABC family proteins, ABCB-1 and ABCC-1 observed in DEHP-exposed clones compared to doxorubicin-resistant (DoxR) and parental MDA-MB-231 cells. A viability assay showed enhanced multidrug resistance in DEHP-exposed clones against Dox, topotecan, and irinotecan. Inhibition of ABC transporters with tariquidar, enhanced drug cytotoxicity through increased drug accumulation reversing acquired multidrug resistance in MDA-MB-231 breast cancer cells. Tariquidar enhanced Dox cytotoxicity by increasing intracellular ROS production leading to caspase-3 mediated apoptosis. Activation of PI3K/Akt signaling enhanced proliferation and growth of DEHP-exposed MDA-MB-231 cells. Overall, long-term DEHP exposure resulted in acquired multidrug resistance by upregulating ABCB-1 and ABCC1; apart from proliferation PI3K/Akt may be responsible for acquired drug resistance through ABC transporter upregulation. Targeting ABCB1 and ABCC1 with tariquidar may be a promising strategy for reversing the acquired multidrug resistance of triple-negative breast cancer cells.

Pemphigus vulgaris (PV) is an autoimmune disease in which the autoantibody, immunoglobulin G, is directed against the keratinocytes in the epidermis. The classic presentations of PV are flaccid vesicles or bullae over the oral mucosa, trunk, groin, and extremities. The age of onset is usually between 40 and 60 years, and cases of PV in children or adolescent patients are rare. Here, we present a 17-year-old boy who had painful oral ulcers for 3 months initially and bullae spreading to the whole body in the following days. Paraneoplastic pemphigus was another differential diagnosis due to the atypical appearance of the skin lesion. However, PV was confirmed by hematoxylin and eosin staining and immunofluorescence examination of the skin biopsy specimens. The patient had a good response to corticosteroid treatment and the immunosuppressive agent, rituximab.

The leaf photosynthesis and nitrogen (N) translocation in three large-spike lines and control cultivar (Xi'nong 979) of winter wheat (Triticum aestivum L.) were studied in 2010–2011 and 2011–2012. The objectives of this study were to investigate the differences in the physiological characteristics of large-spike lines and control cultivar and identify the limiting factors that play a role in improving the yield of breeding materials. The average yield, grain number per spike, kernel weight per spike, and 1000-kernel weight of the large-spike lines were 16.0, 26.8, 42.6, and 15.4%, respectively, significantly higher than those of control. The average photosynthetic rates (Pn) were not significant between the large-spike lines and control cultivar during the active growth period. The average PSII maximum energy conversion efficiency (Fv/Fm), PSII actual quantum efficiency (ΦPS??), photochemical quenching coefficient (qP), PSII reaction center activity (Fv‘/Fv‘) and water-use efficiency (WUE) of the large-spike lines were 1.0, 5.1, 3.6, 0.8, and 43.4%, respectively, higher than those of the control during the active growth stages. The N distribution proportions in different tissues were ranked in the order of grains

Isoflurane is a widely used inhaled anesthetic in the clinical setting. However, the mechanism underlying its effect on consciousness is under discussion. Therefore, we investigated the effect of isoflurane on the hippocampus and cortex using an in vivo field recording approach. Our results showed that 1.3%, 0.8%, and 0.4% isoflurane exerted an inhibitory influence on the mouse hippocampus and cortex. Further, high frequency bands in the cortex and hippocampus showed greater suppression with increasing isoflurane concentration. Our findings suggest that in vivo field recordings can monitor the effect of isoflurane anesthesia on the mouse cortex and hippocampus.

An amendment to this paper has been published and can be accessed via the original article.

Background/Objective: This report describes the 2014 consensus of the Taiwanese Dermatological Association (TDA) regarding the treatment of atopic dermatitis (AD). The TDA consensus is distributed to practices throughout Taiwan to provide recommendations for therapeutic approaches for AD patients to improve their quality of life. Methods: The information in the consensus was agreed upon by a panel of national experts at TDA AD consensus meetings held on March 16, May 4, and June 29, 2014. The consensus was in part based on the 2013 Asia–Pacific AD guidelines and the guidelines of the American Academy of Dermatology, with modification to reflect the clinical practice in Taiwan. Results: The amendments were drafted after scientific discussions focused on the quality of evidence, risk, and benefits; all the consensus contents were voted on by the participating dermatologists, with approval by at least 75% for inclusion. Conclusion: The consensus provides a comprehensive overview of treatment for AD, with some local and cultural considerations for practitioners in Taiwan, especially the use of wet dressings/wraps, systemic immunomodulatory agents, and complementary therapies.

AIM:To discuss and study the effect of trabeculectomy combined with compound Xueshuantong capsules on visual function damage in patients with acute angle-closure glaucoma. METHODS:One hundred patients(120 eyes)with acute angle-closure glaucoma treated in our hospital from March 2010 to October 2014 were selected, which were divided according to the double blind method into the observation group and the control group. Fifty-two cases(60 eyes)of the observation group were treated with trabeculectomy combined with compound Xueshuantong capsules, 48 cases(60 eyes)of the control group were treated with trabeculectomy. Visual acuity and visual field recovery in the two groups were compared.RESULTS:At 3mo after operation, intraocular pressure(IOP)returned to normal, the visual acuity of observation group increased by 0.16±0.02, which of control group increased by 0.09±0.01, and the difference was significant(PPPCONCLUSION:Trabeculectomy combined with compound Xueshuantong capsules for patients with acute angle-closure glaucoma can effectively improve the visual acuity, expand the scope of vision, and reduce the incidence of complications.

Background/Objectives: Paraneoplastic pemphigus (PNP) is a rare mucocutaneous disease with a high mortality rate. It is defined by polymorphic mucocutaneous manifestations, particular histological features, characteristic results of direct and indirect immunofluorescence examinations, presences of specific autoantibodies, and associations with underlying neoplasms. However, currently, there is no existing study regarding the characteristics of PNP patients in Taiwan. In this study, we report a case series and try to determine the specific presentations of PNP patients in Taiwan. Materials and methods: PNP patients treated in a referral center in northern Taiwan from 1998 to 2012 were retrospectively recruited. The clinical manifestations, histopathological features, findings of direct and indirect immunofluorescence, results of immunoblotting, and all relevant clinical information were collected. Results: Eleven patients were identified with an average age of 62 years. Polymorphic mucocutaneous manifestations were observed in almost all patients. The most common presentation was pemphigus-like lesions, followed by lichen planus-like lesions. All patients had recalcitrant oral mucosal lesions. Five and four patients had genital and eye involvements, respectively. The mostly associated neoplasm is Castleman’s disease, followed by malignant thymoma. Acantholysis is the mostly observed histological features, followed by lichenoid dermatitis and interface dermatitis. Depositions of immunoglobulins or complements on the surface of keratinocytes or along basement membrane zone were found in eight and seven patients, respectively. Respiratory symptoms presented in eight patients. Despite intensive treatments, seven patients expired. Conclusion: PNP in Taiwanese patients has a high association with Castleman’s disease or malignant thymoma. Complete laboratory examinations and thorough investigations for occult neoplasms are mandatory to establish a diagnosis in patients with clinical suspicions of PNP.