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BACKGROUND: Patients with malignant pleural effusion (MPE) are usually treated with an indwelling pleural catheter (IPC) or pleurodesis. However, most do not achieve a satisfactory control rate of pleural effusion and have poor prognosis. Distilled water has cytocidal effects of hypotonic shock and can result in the lysis of cancer cells which was used in surgery to eradicate cancer cells. However, there is no study focusing on the efficacy of intrapleural hyperthemic perfusion for MPE under video-assisted thoracoscopic surgery (VATS). This study explored the efficacy and safety of intrapleural hyperthermic perfusion (IHP) with distilled water in patients with MPE. METHODS: In this retrospective, single-arm trial, patients admitted to department of cardiothoracic surgery of Taizhou hospital and diagnosed with MPE caused by non-small cell lung cancer from January 2014 and December 2018 were included. The clinical characteristics including age, gender smoking history, Karnofsky score, volume of pleural effusion, TNM cancer stage, pathology, genetic test of patients were collected. Patients were treated with hyperthermic perfusion. The pleural cavity was perfused with 43.0 ℃ distilled water for 60 minutes under video-assisted thoracic surgery (VATS). The efficacy of treatment was defined as follows: (I) complete remission (CR; no recurrence of pleural effusion after IHP for at least four weeks); (II) partial remission (PR; pleural effusion was decreased by 50% and the condition lasted for 4 weeks; or (III) no remission (NR; no decrease in pleural effusion). Kaplan-Meier method with a log-rank test was used for survival analysis. Cox proportional hazards regression models were applied to perform univariate and multivariate analyses RESULTS: From January 2014 through December 2018, 30 patients with MPE caused by non-small cell lung cancer (NSCLC) were treated with hyperthermic perfusion. There were no serious reportable clinical complications associated with the procedure. The response rate was 96.7%, with 63.3% experiencing PR and 33.3% achieving CR. The overall survival (OS) ranged from 2 to 46 months. The median survival was 12 months. CONCLUSIONS: IHP proved to be a feasible and safe strategy for patients with MPE in our study but it still needs to be verified with a larger, prospective and randomized trial in the future.

Background: Patients with malignant pleural effusion (MPE) have a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy but with a not satisfactory control rate of pleural effusion. This study aims to report the effect of intrapleural hyperthermic perfusion for MPE which is a standard practice at our center.Methods: This is a retrospective study of consecutive patients with MPE treated with hyperthermic perfusion from one single Institute. The procedure was done by perfusing the pleural cavity under video-assisted thoracoscope with 43.0°C distilled water using a standard extracorporeal circuit for 60 minutes. The efficacy of treatment was classified as follows: 1. complete response (CR; no re-accumulation of pleural effusion after IPH for at least four weeks); 2. partial response (PR; pleural effusion was reduced by 50% and this situation was sustained for four weeks; 3. no consequence (NC; pleural effusion was not reduced.Results: From January 2014 through December 2018, a total of 31 patients with MPE were treated using this technique. There were no serious reportable clinical complications associated with the procedures. The response rate was 100%, with 67.7% of PR and 32.3% of CR. The survival time ranged from 2 to 46 months, with a median survival of 12 months. The survival time of the patients received TKI treatment after IHP ranged from 13 to 45 months, with a median survival of 28 months. Multivariable analysis showed that TKI treatment (P=0.013) and male gender (P=0.004) were independent prognosis factors.Conclusions: Intrapleural hyperthermic perfusion is a feasible and safe strategy for patients with malignant pleural effusion.

PURPOSE This study aims to compare the incidence of complications when using a new approach to secure an indwelling peripheral venous catheter (PVC), involving tying of the tube with a surgical knot at two places and several layers of elastic adhesive bandage, with a standard approach using sterile, transparent, and protective film. METHODS This study enrolled 311 consecutive adults undergoing thoracoscopic lobectomy under general anesthesia at Taizhou Hospital of Zhejiang Province between October 2017 and May 2018. Patients were randomized to experimental and control groups and were followed for up to 72 hours. The primary endpoint was dislodgement of the PVC. Secondary endpoints were blood in the catheter; analgesia pump obstruction alarm; time taken and cost of PVC replacement; replacement of securing materials and analgesia pump line; and time and cost of replacing them. All adverse events were recorded. FINDINGS Final analysis included 248 patients (experimental group: n = 126; control group: n = 122). PVC dislodgement was less frequent in the experimental group than in the control group. In the control group, 78.7% of patients required replacement of securing materials (costing 37 cents each time) and 13.1% required PVC replacement (costing 3.6 dollars each time), necessitating additional nursing time. No patients in the experimental group required replacement of the PVC or securing materials. Blisters were less common in the experimental group than in the control group (0% vs 9.84%, P < .001). No patients had limb edema. CONCLUSIONS This new method of securing an analgesia pump line can reduce traction on the indwelling PVC, lowering the dislodgement rate.

The texture quality of French fries is critical to the potato processing industry. Sensory evaluation via testing mouth sensation or by visual and finger spinning inspection are the primary methods to assess French fry texture quality. Instrumental texture analysis has not been practically used due to data inconsistency. This study aimed to minimize variations of instrumental analysis and identify instrumental parameters with strong correlations to a sensory evaluation to enhance the effectiveness of the texture quality assessment. This research was carried out on an industrial scale and utilized 10 potato varieties to increase the texture variation of samples. The sensory evaluation by the visual and finger spinning inspection was performed following industrial procedures and standards. Results showed instrumental crispness and crunchiness, as represented by the slope of the first significant fracture and the number of fractures of the force-distance curve in a cut test with a T-42 blade, were strongly correlated with desirable sensory attributes. Microstructure examination revealed that a low level of crust compactness was associated with instrumental crispness and crunchiness. The procedure advanced in this study had a small data variation and concluded that instrumental crispness and crunchiness are strong indicators of premium French fry texture quality.

Primary cilia are required for proper Sonic Hedgehog (Shh) signaling in mammals. However, their role in the signal transduction process remains unclear. We have identified sister of open brain ( sopb ), a null allele of mouse Intraflagellar transport protein 122 ( Ift122 ). IFT122 negatively regulates the Shh pathway in the cilium at a step downstream of the Shh ligand and the transmembrane protein Smoothened, but upstream of the Gli2 transcription factor. Ift122 sopb mutants generate primary cilia, but they show features of defective retrograde intraflagellar transport. IFT122 controls the ciliary localization of Shh pathway regulators in different ways. Disruption of IFT122 leads to accumulation of Gli2 and Gli3 at cilia tips while blocking the ciliary localization of the antagonist TULP3. Suppressor of Fused and Smoothened localize to the cilium through an IFT122-independent mechanism. We propose that the balance between positive and negative regulators of the Shh pathway at the cilium tip controls the output of the pathway and that Shh signaling regulates this balance through intraflagellar transport.

The effects of polyethylene glycol 20000 (PEG 20000) on the intestinal absorption of prednisolone, methylprednisolone and quinidine, three P-glycoprotein (P-gp) substrates, across the isolated rat intestinal membranes were examined by an in-vitro diffusion chamber system. The serosal-to-mucosal (secretory) transport of these P-gp substrates was greater than their mucosal-to-serosal (absorptive) transport, indicating that their net movement across the intestinal membranes was preferentially in the secretory direction. The polarized secretory transport of these drugs was remarkably diminished and their efflux ratios decreased in the presence of PEG 20000. In addition, PEG 20000 did not affect the transport of Lucifer yellow, a non-P-gp substrate. The intestinal membrane toxicity of PEG 20000 was evaluated by measuring the release of alkaline phosphatase (ALP) and protein from the intestinal membranes. The release of ALP and protein was enhanced in the presence of 20 mM sodium deoxycholate (NaDC), a positive control, while these biological parameters did not change in the presence of 0.1–5% (w/v) PEG 20000. These findings indicated that the intestinal membrane damage caused by PEG 20000 was not a main reason for the enhanced absorptive transport of these P-gp substrates in the presence of PEG 20000. Furthermore, the transepithelial electrical resistance (TEER) of rat jejunal membranes in the presence or absence of PEG 20000 was measured by a diffusion chamber method. PEG 20000 (0.1–5.0 % w/v) did not change the TEER values of the rat jejunal membranes, indicating that the increase in the absorptive transport of these P-gp substrates might not be due to the increased transport of these P-gp substrates via a paracellular pathway caused by PEG 20000. Finally, the effect of PEG 20000 on the intestinal absorption of quinidine was examined by an in-situ closed-loop method. The intestinal absorption of quinidine was significantly enhanced in the presence of 0.1-1.0% (w/v) PEG 20000. These findings suggest that PEG 20000 might be a useful excipient to improve the intestinal absorption of quinidine, which is mainly secreted by a P-gp-mediated efflux system in the intestine.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that transcriptionally regulate responsive genes by binding to the peroxisome proliferator response elements. Protein(s) interacting with PPAR isoforms (alpha, delta, and gamma) may modulate the PPAR-mediated transcriptional activation. Using a yeast two-hybrid system to screen a rat liver cDNA library, we have identified rat deoxyuridine-triphosphatase (dUTPase, EC 3.6. 1.23) as a PPARalpha-interacting protein. This cDNA encodes a polypeptide of 203 amino acids; the C-terminal 141-amino acid segment of this protein corresponds to the full-length human enzyme, which exhibits 92% identity with human dUTPase; the N-terminal extra 62-amino acid residue region is arginine-rich. In vitro binding assays indicate that rat dUTPase interacts with all three isoforms of mouse PPAR, but not with retinoid X receptor and thyroid hormone receptor. Interaction of PPARalpha with dUTPase is with the N-terminal 62-amino acid segment of rat dUTPase. Full-length rat dUTPase prevents PPAR-retinoid X receptor heterodimerization resulting in an inhibition of PPAR activity in a ligand-independent manner. Immunostaining of human kidney tsA201 cells, transiently expressing dUTPase showed that this protein is present predominantly in the cytoplasm but translocates into the nucleus with PPARalpha when PPARalpha is coexpressed with dUTPase. Northern blot hybridization shows that rat dUTPase is encoded by an abundant 1kilobase mRNA species present in all rat tissues. The identification of dUTPase as a PPAR-interacting protein suggests a possible link between tumorigenic peroxisome proliferators and the enzyme system involved in the maintenance of DNA fidelity.

Human liver peroxisomes contain two acyl-CoA oxidases, namely, palmitoyl-CoA oxidase and a branched chain acyl-CoA oxidase. The palmitoyl-CoA oxidase (ACOX) oxidizes the CoA esters of straight chain fatty acids and prostaglandins and donates electrons directly to molecular oxygen, thereby producing H2O2. The inducibility of this H2O2-generating ACOX in rat and mouse liver by peroxisome proliferators and the postulated role of the resulting oxidative stress in hepatocarcinogenesis generated interest in characterizing the structure and function of human ACOX. We have constructed a full-length cDNA encoding a 660-amino acid residue human ACOX and produced a catalytically active human ACOX protein at high levels in Spodoptera frugiperda (Sf9) insect cells using the baculovirus vector. Immunoblot analysis demonstrated that the full-length 72-kDa polypeptide (component A) was partially processed into its constituent 51-kDa (component B) and 21-kDa (component C) products, respectively. Recombinant protein (approximately 20 mg/l x 10(9) cells) was purified to homogeneity by a single-step procedure on a nickel-nitrilo-triacetic acid affinity column. Using the purified enzyme, Km and Vmax values for palmitoyl-CoA were found to be 10 microM and 1.4 units/mg of protein, respectively. The maximal activities for saturated fatty acids were observed with C12-18 substrates. The overexpressed human ACOX protein was identified in the cytoplasm of the insect cells by immunocytochemical staining. Individual expression of either the truncated ACOX 51-kDa (component B) or the 21-kDa (component C) revealed lack of enzyme activity, but co-infection of the insect cells with recombinant viruses expressing components B and C resulted in the formation of an enzymatically active heterodimeric B+C complex which could subsequently be inactivated by dissociating with detergent.

The effect of Wellsolve, a new solubilizing agent, on the function of intestinal membrane barrier and transporters including P-glycoprotein (P-gp) and peptide transporter (PEPT1) was examined by an in vitro diffusion chamber and an in situ closed loop method. The model drugs used in this study were 5(6)-carboxyfluorescein (CF), rhodamine123 (a P-glycoprotein substrate), cephalexin (a typical substrate for PEPT1) and griseofulvin (a BCS Class II drug). Intestinal absorption of CF was not affected by the addition of 1—10% (v/v) Wellsolve, while 20% (v/v) Wellsolve significantly enhanced its intestinal absorption by the in situ absorption study. Therefore, this finding suggested that high concentration of Wellsolve might alter the intestinal barrier function. The mucosal to serosal (absorptive) and serosal to mucosal (secretory) transport of rhodamine123 was significantly inhibited in the presence of 5.0—20% (v/v) of Wellsolve, suggesting that Wellsolve might not affect the function of P-gp in the intestine. The intestinal transport of cephalexin was not affected in the presence of Wellsolve, suggesting that this solubilizing agent might not change the function of PEPT1 in the intestine. In the toxicity studies, we found that 1—10% (v/v) Wellsolve did not change the release of lactate hydrogenase (LDH) and protein from the intestinal membranes. Furthermore, intestinal absorption of griseofulvin in the presence of 10% (v/v) Wellsolve significantly increased as compared with the control. In summary, Wellsolve at lower concentrations might be a potent and safe solubilizing agent for improving the solubility and absorption of poorly water-soluble drugs including griseofulvin.

Peroxisome proliferator-activated receptor (PPAR) forms a heterodimer with retinoid X receptor (RXR) that binds to the peroxisome proliferator responsive element (PPRE) to regulate the expression of target genes. PPRE of the rat enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD) gene has previously been shown to consist of three imperfect TGACCT half-sites and form two distinct complexes (C1 and C2) with the nuclear extracts from H4IIEC3 cells. The present study identifies another imperfect TGACCT motif involved in the PPAR/RXR-mediated trans-activation process and demonstrates that these four imperfect TGACCT motifs constitute an unique binding site consisting of two DR1 elements overlapping a DR2 element. PPAR and RXR cooperatively bind the two DR1 elements to form C1 complex or bind DR2 element to form C2 complex with a 1:1 ratio. Saturation of the HD PPRE probes with receptor proteins cannot convert the heterodimeric C2 complex to the higher order C1 complex, suggesting that they are formed independently. Transfection analyses indicate that mutation of any one of these TGACCT motifs or truncation of the entire HD PPRE into a separate DR1 and DR2 element significantly reduced the transcriptional response of HD PPRE to peroxisome proliferators. The rat HD PPRE differentially binds with one or two PPAR/RXR heterodimers providing the peroxisome proliferator signaling pathway with two levels of response.