Mutant U2AF1-Induced Mis-Splicing of mRNA Translation Genes Confers Resistance to Chemotherapy in Acute Myeloid Leukemia.

Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multiomics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1S34F and U2AF1Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA sequencing. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway. SIGNIFICANCE: U2AF1 mutations induce the integrated stress response by disrupting splicing of mRNA translation genes that improves AML cell fitness to enable resistance to chemotherapy, which can be targeted to improve AML treatment.

The antipsychotic drug pimozide promotes apoptosis through the RAF/ERK pathway and enhances autophagy in breast cancer cells.

The antipsychotic drug pimozide has been demonstrated to inhibit cancer. However, the precise anti-cancer mechanism of pimozide remains unclear. The purpose of this study was to investigate the effects of pimozide on human MCF-7 and MDA-MB-231 breast cancer cell lines, and the potential involvement in the RAF/ERK signaling. The effects of pimozide on cells were examined by 4,5-dimethylthiazol-2-yl-3,5-diphenylformazan, wound healing, colony formation, transwell assays, and caspase activity assay. Flow cytometry and acridine orange and ethidium bromide staining were performed to assess changes in cells. Transmission electron microscopy and monodansylcadaverine staining were used to observe autophagosomes. The cyclic adenosine monophosphate was evaluated using the FRET system. Immunohistochemistry, immunofluorescence, RNA interference, and western blot investigated the expression of proteins. Mechanistically, we focus on the RAF1/ERK signaling. We detected pimozide was docked to RAF1 by Schrodinger software. Pimozide down-regulated the phosphorylation of RAF1, ERK 1/2, Bcl-2, and Bcl-xl, up-regulated Bax, and cleaved caspase-9 to induce apoptosis. Pimozide might promote autophagy by up-regulating cAMP. The enhancement of autophagy increased the conversion of LC3-I to LC3-II and down-regulated p62 expression. But mTOR signaling was not involved in promoting autophagy. The knockdown of RAF1 expression induced autophagy and apoptosis in breast cancer cells, consistent with the results of pimozide or sorafenib alone. Blocked autophagy by chloroquine resulted in the impairment of pimozide-induced apoptosis. These data showed that pimozide inhibits breast cancer by regulating the RAF/ERK signaling pathway and might activate cAMP-induced autophagy to promote apoptosis and it may be a potential drug for breast cancer treatment.

Silver Nanowires-Based Flexible Gold Electrode Overcoming Interior Impedance of Nanomaterial Electrodes.

In the development of nanomaterial electrodes for improved electrocatalytic activity, much attention is paid to the compositions, lattice, and surface morphologies. In this study, a new concept to enhance electrocatalytic activity is proposed by reducing impedance inside nanomaterial electrodes. Gold nanodendrites (AuNDs) are grown along silver nanowires (AgNWs) on flexible polydimethylsiloxane (PDMS) support. The AuNDs/AgNWs/PDMS electrode affords an oxidative peak current density of 50 mA cm-2 for ethanol electrooxidation, a value ≈20 times higher than those in the literature do. Electrochemical impedance spectroscopy (EIS) demonstrates the significant contribution of the AgNWs to reduce impedance. The peak current densities for ethanol electrooxidation are decreased 7.5-fold when the AgNWs are electrolytically corroded. By in situ surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT) simulation, it is validated that the ethanol electrooxidation favors the production of acetic acid with undetectable CO, resulting in a more complete oxidation and long-term stability, while the AgNWs corrosion greatly decreases acetic acid production. This novel strategy for fabricating nanomaterial electrodes using AgNWs as a charge transfer conduit may stimulate insights into the design of nanomaterial electrodes.

Prophylactic supplement with melatonin prevented the brain injury after cardiac arrest in rats.

Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 min asphyxia and followed by manual cardiopulmonary resuscitation. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Survival was significantly higher in the Mel + CA group than the CA group (81 vs. 42%, P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the level of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P < 0.05). Mitochondrial function and integrity were protected in the Mel + CA group compared to the CA group, according to the results of mitochondrial swelling, ΔΨm, ROS production, oxygen consumption rate, and respiratory control rate (P < 0.05). Melatonin increased SIRT3 and downregulated acetylated CypD. The mitochondrial dynamics and autophagy were improved in the Mel + CA group (P < 0.05). Long-term daily prophylactic supplement with melatonin buy the time from brain injury after CA.

Signal Processing and Waveform Re-Tracking for SAR Altimeters on High Mobility Platforms with Vertical Movement and Antenna Mis-Pointing.

Synthetic aperture radar (SAR) altimeters can achieve higher spatial resolution and signal-to-noise ratio (SNR) than conventional altimeters by Doppler beam sharpening or focused SAR imaging methods. To improve the estimation accuracy of waveform re-tracking, several average echo power models for SAR altimetry have been proposed in previous works. However, these models were mainly proposed for satellite altimeters and are not applicable to high-mobility platforms such as aircraft, unmanned aerial vehicles (UAVs), and missiles, which may have a large antenna mis-pointing angle and significant vertical movement. In this paper, we propose a novel semi-analytical waveform model and signal processing method for SAR altimeters with vertical movement and large antenna mis-pointing angles. A new semi-analytical expression that can be numerically computed for the flat pulse response (FSIR) is proposed. The 2D delay-Doppler map is then obtained by numerical computation of the convolution between the proposed analytical function, the probability density function, and the time/frequency point target response of the radar. A novel delay compensation method based on sinc interpolation for SAR altimeters with vertical movement is proposed to obtain the multilook echo, which can optimally handle non-integer delays and maintain signal frequency characteristics. In addition, a height estimation method based on least squares (LS) estimation is proposed. The LS estimator does not have an analytical solution, and requires iterative solving through gradient descent. We evaluate the performance of the proposed estimation strategy using simulated data for typical airborne scenarios. When the mis-pointing angles are within 10 degrees, the normalized quadratic error (NQE) of the proposed model is less than 10-10 and the RMSE of τ obtained by the re-tracking method fitted by the proposed model is less than 0.2 m, which indicates the high applicability of the model and accuracy of the re-tracking method.

A comparative transcriptome analysis of how shrimp endure and adapt to long-term symbiosis with Enterocytozoon hepatopenaei infection.

Enterocytozoon hepatopenaei (EHP) is a prevalent microsporidian pathogen responsible for hepatopancreatic microsporidiosis (HPM) in Litopenaeus vannamei. This infection not only leads to slowed growth in shrimp abut aslo inflicts substantial economic losses in the global aquaculture industry. However, the molecular mechanisms by which EHP influences the host during various infection stages remain unclear. This study employed comparative transcriptomics to examine the effects of EHP infection on Litopenaeus vannamei between early and late stage of infection groups. Utilizing transcriptomic approaches, we identified differentially expressed genes (DEGs) with notable biological significance through the COG, GO, KEGG, GSEA, and Mufzz time-series methodologies. The results reveal that EHP infection considerably influences host gene expression, with marked differences between early and late infection across distinct timeframes. Key processes such as detoxification, cell apoptosis, and lipid metabolism are pivotal during host-parasite interactions. Hexokinase and phosphatidic acid phosphatase emerge as key factors enabling invasion and sustained effects. Cytochrome P450 and glucose-6-phosphate dehydrogenase could facilitate infection progression. EHP significantly impacts growth, especially through ecdysteroids and 17ß-estradiol dehydrogenase. By delineating stage-specific effects, we gain insights into interaction between EHP and Litopenaeus vannamei, showing how intracellular pathogens reprogram host defenses into mechanisms enabling long-term persistence. This study provides a deeper understanding of host-pathogen dynamics, emphasizing the interplay between detoxification, metabolism, immunity, apoptosis and growth regulation over the course of long-term symbiosis.

Genome-wide identification and analysis of the evolution and expression pattern of the SBP gene family in two Chimonanthus species.

BACKGROUND: Chimonanthus praecox and Chimonanthus salicifolius are closely related species that diverged approximately six million years ago. While both C. praecox and C. salicifolius could withstand brief periods of low temperatures of - 15 °C. Their flowering times are different, C. praecox blooms in early spring, whereas C. salicifolius blooms in autumn. The SBP-box (SQUAMOSA promoter-binding protein) is a plant-specific gene family that plays a crucial vital role in regulating plant flowering. Although extensively studied in various plants, the SBP gene family remains uncharacterized in Calycanthaceae. METHODS AND RESULTS: We conducted genome-wide identification of SBP genes in both C. praecox and C. salicifolius and comprehensively characterized the chromosomal localization, gene structure, conserved motifs, and domains of the identified SBP genes. In total, 15 and 18 SBP genes were identified in C. praecox and C. salicifolius, respectively. According to phylogenetic analysis, the SBP genes from Arabidopsis, C. praecox, and C. salicifolius were clustered into eight groups. Analysis of the gene structure and conserved protein motifs showed that SBP proteins of the same subfamily have similar motif structures. The expression patterns of SBP genes were analyzed using transcriptome data. The results revealed that more than half of the genes exhibited lower expression levels in leaves than in flowers, suggesting their potential involvement in the flower development process and may be linked to the winter and autumn flowering of C. praecox and C. salicifolius. CONCLUSION: Thirty-three SBPs were identified in C. praecox and C. salicifolius. The evolutionary characteristics and expression patterns were examined in this study. These results provide valuable information to elucidate the evolutionary relationships of the SBP family and help determine the functional characteristics of the SBP genes in subsequent studies.

Genome-wide identification and analysis of MIKC-type MADS-box genes expression in Chimonanthus salicifolius.

BACKGROUND: MIKC type MADS-box transcription factors are one of the largest gene families and play a pivotal role in flowering time and flower development. Chimonanthus salicifolius belongs to the family Calycanthaceae and has a unique flowering time and flowering morphology compared to other Chimonanthus species, but the research on MIKC type MADS-box gene family of C. salicifolius has not been reported. OBJECTIVE: Identification, comprehensive bioinformatic analysis, the expression pattern of MIKC-type MADS-box gene family from different tissues of C. salicifolius. METHODS: Genome-wide investigation and expression pattern under different tissues of the MIKC-type MADS-box gene family in C. salicifolius, and their phylogenetic relationships, evolutionary characteristics, gene structure, motif distribution, promoter cis-acting element were performed. RESULTS: A total of 29 MIKC-type MADS-box genes were identified from the whole genome sequencing. Interspecies synteny analysis revealed more significant collinearity between C. salicifolius and the magnoliids species compared to eudicots and monocots. MIKC-type MADS-box genes from the same subfamily share similar distribution patterns, gene structure, and expression patterns. Compared with Arabidopsis thaliana, Nymphaea colorata, and Chimonanthus praecox, the FLC genes were absent in C. salicifolius, while the AGL6 subfamily was expanded in C. salicifolius. The selectively expanded promoter (AGL6) and lack of repressor (FLC) genes may explain the earlier flowering in C. salicifolius. The loss of the AP3 homologous gene in C. salicifolius is probably the primary cause of the morphological distinction between C. salicifolius and C. praecox. The csAGL6a gene is specifically expressed in the flowering process and indicates the potential function of promoting flowering. CONCLUSION: This study offers a genome-wide identification and expression profiling of the MIKC-types MADS-box genes in the C. salicifolius, and establishes the foundation for screening flowering development genes and understanding the potential function of the MIKC-types MADS-box genes in the C. salicifolius.

Identification and validation of a novel CD8+ T cell-associated prognostic model based on ferroptosis in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly aggressive cancer with great heterogeneity and variability in prognosis. Though European Leukemia Net (ELN) 2017 risk classification has been widely used, nearly half of patients were stratified to "intermediate" risk and requires more accurate classification via excavating biological features. As new evidence showed that CD8+ T cell can kill cancer cells through ferroptosis pathway. We firstly use CIBERSORT algorithm to divide AMLs into CD8+ high and CD8+ low T cell groups, then 2789 differentially expressed genes (DEGs) between groups were identified, of which 46 ferroptosis-related genes associated with CD8+ T cell were sorted out. GO, KEGG analysis and PPI network were conducted based on these 46 DEGs. By jointly using LASSO algorithm and Cox univariate regression, we generated a 6-gene prognostic signature comprising VEGFA, KLHL24, ATG3, EIF2AK4, IDH1 and HSPB1. Low-risk group shows a longer overall survival. We then validated the prognostic value of this 6-gene signature using two independent external datasets and patient sample collection dataset. We also proved that incorporation of the 6-gene signature obviously enhanced the accuracy of ELN risk classification. Finally, gene mutation analysis, drug sensitive prediction, GSEA and GSVA analysis were conducted between high-risk and low-risk AML patients. Collectively, our findings suggested that the prognostic signature based on CD8+ T cell-related ferroptosis genes can optimize the risk stratification and prognostic prediction of AML patients.

Measuring college belongingness: Structure and measurement of the Sense of Social Fit Scale.

Sense of belonging is theorized to be a fundamental human need and has been shown to have important implications in many domains of life, including academic achievement. The Sense of Social Fit scale (SSF; Walton & Cohen, 2007) is widely used to assess college belongingness, particularly to study differences in academic experiences along lines of gender and race. Despite its wide use, the instrument's latent factor structure and measurement invariance properties have not been reported in the published literature to date. Consequently, researchers regularly use subsets of the SSF's items without psychometric justification. Here, we explore and validate the SSF's factor structure and other psychometric properties, and we provide recommendations about how to score the measure. A one-factor model in Study 1 showed poor fit, and exploratory factor analyses extracted a four-factor solution. Study 2's confirmatory factor analyses demonstrated superior fit of a bifactor model with four specific factors (from Study 1) and one general factor. Ancillary analyses supported a total scale scoring method for the SSF and did not support computing raw subscale scores. We also tested the bifactor model's measurement invariance across gender and race, compared latent mean scores between groups, and established the model's criterion and concurrent validity. We discuss implications and suggestions for future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparative transcriptome analysis of non-germinated and germinated spores of Enterocytozoon hepatopenaei (EHP) in vitro.

Enterocytozoon hepatopenaei (EHP), an obligate intracellular parasite classified as microsporidia, is an emerging pathogen with a significant impact on the global shrimp aquaculture industry. The understanding of how microsporidia germinate has been a key factor in exploring its infection process. However, the germination process of EHP was rarely reported. To gain insight into the germination process, we conducted a high-throughput sequencing analysis of purified EHP spores that had undergone in vitro germination treatment. This analysis revealed 137 differentially expressed genes, with 84 up-regulated and 53 down-regulated genes. While the functions of some of the genes remain unknown, this study provides important data on the transcriptomic changes before and after EHP germination, which can aid in further studies on the EHP infection mechanism.

Intestinal Microbiota Differences in Litopenaeus vannamei Shrimp between Greenhouse and Aquaponic Rearing.

The sustainability of shrimp aquaculture can be achieved through the development of greenhouse and aquaponic rearing modes, which are classified as heterotrophic and autotrophic bacterial aquaculture systems. However, there have been few investigations into the discrepancies between the intestinal and water microbiota of these two rearing methods. In this study, we collected shrimp samples from greenhouse-rearing (WG) and aquaponic-rearing (YG) ponds, and water samples (WE, YE), and investigated the intestinal and water microbiota between the two rearing modes. The results, through alpha and beta diversity analyses, reveal that there was basically no significant difference between shrimp intestine WG and YG (p > 0.05) or between rearing water WE and YE (p > 0.05). At the phylum and genus levels, the common bacteria between WE and WG differed significantly from those of YE and YG. The analysis of the top six phyla shows that Proteobacteria and Patescibacteria were significantly more abundant in the WG group than those in the YG group (p < 0.05). Conversely, Actinobacteriota, Firmicutes, and Verrucomicrobiota were significantly more abundant in the YG group than those in the WG group (p < 0.05). Venn analysis between WE and WG shows that Amaricoccus, Micrococcales, Flavobacteriaceae, and Paracoccus were the dominant bacteria genera, while Acinetobacter, Demequina, and Rheinheimera were the dominant bacteria genera between YE and YG. Pathways such as the biosynthesis of secondary metabolites, microbial metabolism in different environments, and carbon metabolism were significantly more upregulated in WG than those in YG (p < 0.05). In addition, pathways such as sulfate, chloroplast, phototrophy, and the nitrogen metabolism were significantly different between the WE and YE samples. These findings suggest that the greenhouse mode, a typical heterotrophic bacterial model, contains bacterial flora consisting of Amaricoccus, Micrococcales, Flavobacteriaceae, and other bacteria, which is indicative of the biological sludge process. Conversely, the aquaponic mode, an autotrophic bacterial model, was characterized by Acinetobacter, Demequina, Rheinheimera, and other bacteria, signifying the autotrophic biological process. This research provides an extensive understanding of heterotrophic and autotrophic bacterial aquaculture systems.

Enhanced efficiency and mechanism of low-temperature biochar on simultaneous removal of nitrogen and phosphorus by combined heterotrophic nitrification-aerobic denitrification bacteria.

In this study, three strains of heterotrophic nitrification-aerobic denitrification (HN-AD) capable of simultaneously removing phosphorus were isolated from activated sludge, and low-temperature coconut shell biochar was prepared. The metabolic effects of combined HN-AD bacteria on the total nitrogen (TN) and total phosphorus (TP) were investigated, and the enhanced efficiency and mechanism of low-temperature biochar on the combined bacteria were also explored. The results indicated that the combined bacteria could adapt to environmental impacts and multiple nitrogen sources. The low-temperature biochar containing more aliphatic carbon and oxygen-containing functional groups enhanced the metabolic activity of combined HN-AD bacteria and accelerated the electron transfer process during nitrogen and phosphorus degradation. The removal efficiencies of TN and TP increased by 68% and 88%, respectively, in the treatment of actual sewage by biochar attached with combined bacteria. The findings form a basis for the engineering utilization of HN-AD and are of great practical significance.

Effect of chitooligosaccharide on the inhibition of SARS-CoV-2 main protease.

BACKGROUND: The main protease (Mpro) is a crucial target for severe acute respiratory syndrome coronavirus (SARS-CoV-2). Chitooligosaccharide (CS) has broad-spectrum antiviral activity and can effectively inhibit the activity of SARS-CoV. Here, based on the high homology between SARS-CoV-2 and SARS-CoV, this study explores the effect and mechanism of CS with various molecular weights on the activity of SARS-CoV-2 Mpro. METHODS: We used fluorescence resonance energy transfer (FRET), UV-Vis, synchronous fluorescence spectroscopy, circular dichroism (CD) spectroscopy and computational simulation to investigate the molecular interaction and the interaction mechanism between CS and SARS-CoV-2 Mpro. RESULTS: Four kinds of CS with different molecular weights significantly inhibited the activity of Mpro by combining the hydrogen bonding and the salt bridge interaction to form a stable complex. Glu166 appeared to be the key amino acid. Among them, chitosan showed the highest inhibition effect on Mpro enzyme activity and the greatest impact on the spatial structure of protein. Chitosan would be one of the most potential anti-viral compounds. CONCLUSION: This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.

Transcriptome analysis of hepatopancreas and gills of Palaemon gravieri under salinity stress.

Salinity is an important factor in the aquatic environment, and its fluctuations always result in osmotic stress, which affects the survival, distribution, and physiological activities of crustaceans. Crustaceans counter them through osmoregulation, which consists of many mechanisms. Palaemon gravieri is an important economic species in Palaemonidae, widely distributed in the southern East China Sea and the China Yellow Sea, and has a good adaptability to salinity stress. Currently, there are only a few studies on the effects of salinity on P. graviera. Therefore, it is particularly important to study the molecular responses of P. gravieri to salinity fluctuations. In this study, P. gravieri was treated with salinities of 10, 25, and 40, and the hepatopancreas and gills of shrimp in the different salinity groups were sampled after 24 h. The samples were used for RNA extraction and transcriptome analysis. In total, 80,994 unigenes were obtained, of which 19,114 were annotated. The differences in gene expression between different tissues at the same salinity were more significant. Many metabolism-related genes were downregulated in the gills, such as beta-hexosaminidase subunit alpha (HEXA), 10-formyltetrahydrofolate dehydrogenase (ALDH1L1), and Alcohol dehydrogenase class-3 (ADH5). Scanning transmission electron microscope analysis showed that the expression levels of some stress-(but not salinity stress) related genes changed after stress (mostly upregulated), suggesting the existence of secondary stress. Gene set enrichment analysis (GSEA) focused on the expression of transporters in osmoregulation, and the results showed that they mainly played a role in the gills, but ATP-binding cassette (ABC) transporters were more active in the hepatopancreas. This study showed that the response of P. gravieri to salinity change was different not only between the hepatopancreas and gills, but also between low salinity and higher salinity, and the ion transport-related genes were mainly expressed in the gills. Overall, these results improve our understanding of salt tolerance mechanism in P. gravieri.

Bootstrap-Based Between-Study Heterogeneity Tests in Meta-Analysis.

Meta-analysis combines pertinent information from existing studies to provide an overall estimate of population parameters/effect sizes, as well as to quantify and explain the differences between studies. However, testing between-study heterogeneity is one of the most challenging tasks in meta-analysis research. Existing methods for testing heterogeneity, such as the Q test and likelihood ratio (LR) test, have been criticized for their failure to control Type I error rate and/or failure to attain enough statistical power. Although better reference distribution approximations have been proposed in the literature, their application is limited. Additionally, when the interest is to test whether the size of the heterogeneity is larger than a specific level, existing methods are far from mature. To address these issues, we propose new heterogeneity tests. Specifically, we combine bootstrap methods with existing heterogeneity tests (i.e., the maximum LR test, the restricted maximum LR test, and the Q test) to overcome the reference distribution issue and denote them as B-ML-LRT, B-REML-LRT, and B-Q, respectively. Simulation studies were conducted to examine and compare the performance of the proposed methods with the regular LR test, the regular Q test, and the Kulinskaya's improved Q test in both random- and mixed-effects meta-analyses. Based on the results of Type I error rates and statistical power, B-REML-LRT is recommended. Additionally, the improved Q test is also recommended when it is applicable. An R package boot.heterogeneity is provided to facilitate the implementation of the proposed tests.

The effects of dexmedetomidine for patient-controlled analgesia on postoperative sleep quality and gastrointestinal motility function after surgery: A prospective, randomized, double-blind, and controlled trial.

Background: Postoperative poor sleep quality and decreased gastrointestinal motility function are common clinical problems. This study investigated the effects of dexmedetomidine (DEX) combined with sufentanil for patient-controlled analgesia (PCA) on postoperative sleep quality and gastrointestinal motility function after surgery in patients with colorectal cancer. Methods: Patients undergoing colorectal cancer surgery were randomly divided into three groups, DEX 0, 200, or 400 µg, each combined with sufentanil 150 µg for PCA immediately after surgery. The primary outcome was sleep quality in the first 7 days after surgery based on the Athens Insomnia Scale (AIS) score. The secondary outcome was postoperative gastrointestinal motility recovery evaluated by the time of first flatus, first feces and first diet. Postoperative pain intensity, side effects and the length of postoperative hospital stay were also compared among groups. The study was registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn/enIndex.aspx, ChiCTR2000032601). Results: Ultimately, 210 cases were included. Sleep quality was better in the DEX 200 µg group and DEX 400 µg group than in the DEX 0 µg group. Overall, in the DEX 200 µg group and DEX 400 µg group, the AIS score (p < 0.05) and the incidence of sleep disturbance (7.3%, 4.5% vs. 19.6%, p < 0.001) were lower than those in the DEX 0 µg group in the first 7 days after surgery. There were no significant differences in postoperative gastrointestinal motility among the three groups in the total surgical categories (p > 0.05). In the laparoscopic surgery patients of each group, the time of postoperative first flatus (p = 0.02) and first feces (p = 0.01) was significantly longer in the DEX 400 µg group than in the DEX 0 µg group. There were no differences in postoperative pain intensity, side effects or length of postoperative hospital stay (p > 0.05). Conclusion: The continuous infusion of DEX (200 or 400 µg) for PCA significantly improved postoperative sleep quality after colorectal cancer surgery. DEX (200 µg) was better at improving postoperative sleep quality without affecting gastrointestinal motility function than DEX (400 µg) in patients who underwent laparoscopic colorectal cancer surgery.

Adjuvant treatment for patients with incidentally resected limited disease small cell lung cancer-a retrospective study.

Background: With the exception of very early-stage small cell lung cancer (SCLC), surgery is not typically recommended for this disease; however, incidental resection still occurs. After incidental resection, adjuvant salvage therapy is widely offered, but the evidence supporting its use is limited. This study aimed to explore proper adjuvant therapy for these incidentally resected SCLC cases. Methods: Patients incidentally diagnosed with SCLC after surgery at the Shanghai Pulmonary Hospital in China from January 2005 to December 2014 were included in this study. The primary outcome was overall survival. Patients were classified into different group according to the type of adjuvant therapy they received and stratified by their pathological lymph node status. Patients' survival was analyzed using a Kaplan-Meier analysis and Cox regression analysis. Results: A total of 161 patients were included in this study. Overall 5-year survival rate was 36.5%. For pathological N0 (pN0) cases (n=70), multivariable analysis revealed that adjuvant chemotherapy (ad-chemo) was associated with reduced risk of death [hazard ratio (HR): 0.373; 95% confidence interval (CI): 0.141-0.985, P=0.047] compared to omission of adjuvant therapy. For pathological N1 or N2 (pN1/2) cases (n=91), taking no adjuvant therapy cases as a reference, the multivariable analysis showed that ad-chemo was not associated with a lower risk of death (HR: 0.869; 95% CI: 0.459-1.645, P=0.666), while adjuvant chemo-radiotherapy (ad-CRT) was associated with a lower risk of death (HR: 0.279; 95% CI: 0.102-0.761, P=0.013). Conclusions: Patients who incidentally receive surgical resection and are diagnosed with limited disease SCLC after resection should be offered adjuvant therapy as a salvage treatment. For incidentally resected pN0 cases, ad-chemo should be considered and for pN1/2 cases, ad-CRT should be received.

Preparation and characterization of sodium cellulose sulfate/chitosan composite films loaded with curcumin for monitoring pork freshness.

Colorimetric films were prepared by incorporating curcumin into a sodium cellulose sulfate/chitosan composite. The morphology mechanical, and water vapor properties of the films were investigated, and their practical use in pork preservation was evaluated. The formula with the same charge ratio of sodium cellulose sulfate and chitosan had the highest tensile strength (TS). After the addition of curcumin, the tensile strength increased, whereas the water vapor permeability (WVP) decreased. The colorimetric film showed distinguishable color changes between the pH ranges of 3-10. The colorimetric film packaging extended the shelf life of the pork samples by 4 days. Moreover, the composite films were able to effectively monitor pork freshness. In conclusion, curcumin incorporated into sodium cellulose sulfate/chitosan composite films may have great potential in food packaging.