A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.

Association between the Reduced Expression of RECK and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a recently discovered inhibitor of matrix metalloproteinase (MMP). There is a large number of chronic obstructive pulmonary disease (COPD) patients worldwide; however, the role of RECK on COPD has not been studied. This study explored the expression of RECK in COPD patients and its effect on neutrophil function to provide a new scientific basis for the prevention and treatment of COPD. METHOD: Fifty patients with acute exacerbation of COPD and fifty healthy controls were enrolled in the study. RECK was detected in lung tissue, sputum, and plasma of subjects as well as in BEAS-2B cells stimulated with cigarette smoke extract (CSE) by immunohistochemistry, ELISA, and qRT-PCR. Meanwhile, lung function (FEV1%pred) and inflammatory cytokines (IL-6 and IL-8) were examined, and correlation analysis was performed with RECK expression. The effect of RECK on proliferation, apoptosis, migration, and inflammatory cytokines and its potential mechanism was further quantified by neutrophil stimulated with recombinant human RECK protein (rhRECK) combined with CSE using CCK8, flow cytometry, Transwell assay, qRT-PCR, ELISA, and Western analysis. RESULTS: RECK was mainly expressed on airway epithelial cells in normal lung tissue and was significantly diminished in COPD patients. The levels of RECK in sputum and plasma were also significantly decreased in COPD patients. Pearson correlation analysis showed that RECK level in plasma was positively correlated with FEV1%pred (r = 0.458, p < 0.001) and negatively correlated with IL-6 and IL-8 (r = -0.386, -0.437; p = 0.006, 0.002) in COPD patients. The expression of RECK was decreased in BEAS-2B stimulated with CSE. The migration, inflammation, and MMP-9 expression of neutrophils were promoted by CSE, while inhibited by rhRECK. CONCLUSION: RECK is low expressed in COPD patients and negatively correlated with inflammation. It may inhibit the inflammation and migration of neutrophils by downregulating MMP-9.

Microbial Necromass, Lignin, and Glycoproteins for Determining and Optimizing Blue Carbon Formation.

Coastal wetlands contribute to the mitigation of climate change through the sequestration of "blue carbon". Microbial necromass, lignin, and glycoproteins (i.e., glomalin-related soil proteins (GRSP)), as important components of soil organic carbon (SOC), are sensitive to environmental change. However, their contributions to blue carbon formation and the underlying factors remain largely unresolved. To address this paucity of knowledge, we investigated their contributions to blue carbon formation along a salinity gradient in coastal marshes. Our results revealed decreasing contributions of microbial necromass and lignin to blue carbon as the salinity increased, while GRSP showed an opposite trend. Using random forest models, we showed that their contributions to SOC were dependent on microbial biomass and resource stoichiometry. In N-limited saline soils, contributions of microbial necromass to SOC decreased due to increased N-acquisition enzyme activity. Decreases in lignin contributions were linked to reduced mineral protection offered by short-range-ordered Fe (FeSRO). Partial least-squares path modeling (PLS-PM) further indicated that GRSP could increase microbial necromass and lignin formation by enhancing mineral protection. Our findings have implications for improving the accumulation of refractory and mineral-bound organic matter in coastal wetlands, considering the current scenario of heightened nutrient discharge and sea-level rise.

Multi-Selenophene Incorporated Thiazole Imide-Based n-Type Polymers for High-Performance Organic Thermoelectrics.

Developing polymers with high electrical conductivity (σ) after n-doping is a great challenge for the advance of the field of organic thermoelectrics (OTEs). Herein, we report a series of thiazole imide-based n-type polymers by gradually increasing selenophene content in polymeric backbone. Thanks to the strong intramolecular noncovalent N⋅⋅⋅S interaction and enhanced intermolecular Se⋅⋅⋅Se interaction, with the increase of selenophene content, the polymers show gradually lowered LUMOs, more planar backbone, and improved film crystallinity versus the selenophene-free analogue. Consequently, polymer PDTzSI-Se with the highest selenophene content achieves a champion σ of 164.0 S cm-1 and a power factor of 49.0 µW m-1 K-2 in the series when applied in OTEs after n-doping. The σ value is the highest one for n-type donor-acceptor OTE materials reported to date. Our work indicates that selenophene substitution is a powerful strategy for developing high-performance n-type OTE materials and selenophene incorporated thiazole imides offer an excellent platform in enabling n-type polymers with high backbone coplanarity, deep-lying LUMO and enhanced mobility/conductivity.

SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy.

OBJECTIVES: The protective role of sodium glucose cotransporter 2 (SGLT2) inhibitors in renal outcomes has been revealed by large cardiovascular outcome trials among patients with type 2 diabetes. However, the effect of SGLT2 inhibitors on lupus nephritis (LN) and its underlying mechanisms remain unknown. METHODS: We applied empagliflozin treatment to lupus-prone MRL/lpr mice to explore the renal protective potential of SGLT2 inhibitors. An SGLT2 knockout monoclonal podocyte cell line was generated using the CRISPR/Cas9 system to examine the cellular and molecular mechanisms. RESULTS: In MRL/lpr mice treated with empagliflozin, the levels of mouse anti-dsDNA IgG-specific antibodies, serum creatinine and proteinuria were markedly decreased. For renal pathology assessment, both the glomerular and tubulointerstitial damages were lessened by administration of empagliflozin. The levels of SGLT2 expression were increased and colocalised with decreased synaptopodin in the renal biopsy samples from patients with LN and MRL/lpr mice with nephritis. The SGLT2 inhibitor empagliflozin could alleviated podocyte injury by attenuating inflammation and enhanced autophagy by reducing mTORC1 activity. Nine patients with LN treated with SGLT2 inhibitors with more than 2 months of follow-up showed that the use of SGLT2 inhibitors was associated with a significant decrease in proteinuria from 29.6% to 96.3%. Moreover, the estimated glomerular filtration rate (eGFR) was relatively stable during the treatment with SGLT2 inhibitors. CONCLUSION: This study confirmed the renoprotective effect of SGLT2 inhibitors in lupus mice, providing more evidence for non-immunosuppressive therapies to improve renal function in classic autoimmune kidney diseases such as LN.

Multi-scale analysis provides insights into the roles of ureide permeases in wheat nitrogen use efficiency.

The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In planta, tissue ureide levels are controlled by the activity of enzymes of the purine degradation pathway and by ureide transporters called ureide permeases (UPS). Little is known about the physiological function of UPS proteins in crop plants, and especially in monocotyledon species. Here, we identified 13 TaUPS genes in the wheat (Triticum aestivum L.) genome. Phylogenetic and genome location analyses revealed a close relationship of wheat UPSs to orthologues in other grasses and a division into TaUPS1, TaUPS2.1, and TaUPS2.2 groups, each consisting of three homeologs, with a total of four tandem duplications. Expression, localization, and biochemical analyses resolved spatio-temporal expression patterns of TaUPS genes, transporter localization at the plasma membrane, and a role for TaUPS2.1 proteins in cellular import of ureides and phloem and seed loading. In addition, positive correlations between TaUPS1 and TaUPS2.1 transcripts and ureide levels were found. Together the data support that TaUPSs function in regulating ureide pools at source and sink, along with source-to-sink transport. Moreover, comparative studies between wheat cultivars grown at low and high N strengthened a role for TaUPS1 and TaUPS2.1 transporters in efficient N use and in controlling primary metabolism. Co-expression, protein-protein interaction, and haplotype analyses further support TaUPS involvement in N partitioning, N use efficiency, and domestication. Overall, this work provides a new understanding on UPS transporters in grasses as well as insights for breeding resilient wheat varieties with improved N use efficiency.

Targeted Therapy of Non-Small Cell Lung Cancer and Liver Cancer: Functional Nanocarriers for the Delivery of Cisplatin and Tissue Factor Pathway Inhibitor-2.

INTRODUCTION: The aim of the study was to construct folic acid-modified PEGylated paramagnetic nanoparticles (MNPs) co-carrying tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP), and to study the molecular-targeting and inhibitory effects of the nanocomposite on non-small cell lung cancer (NSCLC) and liver cancer. METHODS: Nanocomposites were prepared using amino-modified iron oxide nanoparticles as carriers, co-loading CDDP and PEGylated FA/TFPI-2. Transmission electron microscopy, UV absorption spectrum, and dynamic light scattering were employed to characterize the morphology, structure, particle size, and zeta potential of the nanocomposite. The phenylenediamine method was used to detect the loading of CDDP, and the CCK-8 assay was used to detect the toxic effect of the nanocomposite on HUVECs, A549, and NCI-H460 cells. In tumor-bearing mice models, the antitumor effects of the nanocomposites were assessed using TUNEL staining (at the molecular level), reverse transcriptase quantitative polymerase chain reaction (at the gene level), hematoxylin and eosin staining (at the cellular level), and the appearance of the mice models. RESULTS: The synthesized FA-MNP/CDDP/TFPI-2 nanocomposite was uniformly dispersed and spherical in shape (approximate diameter: 10 nm). The zeta potential of particles was -9.44 mV, and the average particle size was 25 nm. The loading amount of CDDP was 70.24 µg/mL (23.33%). The nanocomposite was nontoxic to HUVECs, while it showed a favorable inhibitory effect on A549 and NCI-H460 cells. In vivo experiments in mice demonstrated satisfactory imaging properties and therapeutic effects of nanocomposite against liver cancer. DISCUSSION: FA-MNP/CDDP/TFPI-2 may provide insights for the development of new chemotherapeutic drugs.

Correlation analysis of TGF-ß1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study.

OBJECTIVE: To investigate the potential correlation of transforming growth factor-ß (TGF-ß), matrix metalloprotein 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), Interleukin 1 (IL-1), IL-4, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α) in refractory chronic rhinosinusitis. METHODS: A total of 150 participants were retrospectively included in this study from August 2018 to February 2020. The people enrolled were equally allocated into refractory group (patients with refractory chronic rhinosinusitis), chronic group (patients with chronic rhinosinusitis), and control group (normal people). The level of TGF-ß1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α were recorded. The unconditional multivariate binary logistic regression was used to analyze the factors affecting refractory chronic rhinosinusitis. RESULTS: The Davos score, T&T olfactometer threshold test, and Lund-Mackay CT scores in refractory group were significantly higher than the chronic group (P<0.05). The level of TGF-ß1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in the refractory group were significantly higher than the chronic group and the control group (all P<0.05). Similarly, the level of the above mentioned indexes in the chronic group were significantly higher than the control group (P<0.05). The Davos score, T&T olfactometer threshold test score, Lund-Mackay CT score, and the level of TGF-ß1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α positively correlated with refractory chronic rhinosinusitis. Moreover, the unconditional multivariate binary logistic regression showed that the influencing factors of refractory chronic rhinosinusitis included TGF-ß1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α. CONCLUSION: The findings of the present study provide evidence for TGF-ß1, MMP-9, TIMP-1, IL-4, IL-6, IL-17, and TNF-α as the influencing factors of refractory chronic rhinosinusitis.

Statistical Analysis of the Consistency of HRV Analysis Using BCG or Pulse Wave Signals.

Ballistocardiography (BCG) is considered a good alternative to HRV analysis with its non-contact and unobtrusive acquisition characteristics. However, consensus about its validity has not yet been established. In this study, 50 healthy subjects (26.2 ± 5.5 years old, 22 females, 28 males) were invited. Comprehensive statistical analysis, including Coefficients of Variation (CV), Lin's Concordance Correlation Coefficient (LCCC), and Bland-Altman analysis (BA ratio), were utilized to analyze the consistency of BCG and ECG signals in HRV analysis. If the methods gave different answers, the worst case was taken as the result. Measures of consistency such as Mean, SDNN, LF gave good agreement (the absolute value of CV difference < 2%, LCCC > 0.99, BA ratio < 0.1) between J-J (BCG) and R-R intervals (ECG). pNN50 showed moderate agreement (the absolute value of CV difference < 5%, LCCC > 0.95, BA ratio < 0.2), while RMSSD, HF, LF/HF indicated poor agreement (the absolute value of CV difference ≥ 5% or LCCC ≤ 0.95 or BA ratio ≥ 0.2). Additionally, the R-R intervals were compared with P-P intervals extracted from the pulse wave (PW). Except for pNN50, which exhibited poor agreement in this comparison, the performances of the HRV indices estimated from the PW and the BCG signals were similar.

[Quantitative analysis of the effect of contact pressure on the reflection characteristics of radial pressure wave].

The radial artery pulse wave contains a wealth of physiological and pathological information about the human body, and non-invasive studies of the radial artery pulse wave can assess arterial vascular elasticity in different age groups.The piezoelectric pulse wave transducers were used to non-invasively acquire radial artery pulse waves at different contact pressures in young and middle-aged and elderly populations. The radial artery waveforms were decomposed using a triangular blood flow model fitting method to obtain forward and reflected waves and calculate reflection parameters. Finally a correlation analysis and regression analysis of the contact pressure Psensor with the reflection parameters was carried out. The results showed that the reflection parameters RM, RI and Rd had a strong negative correlation with Psensor in both types of subjects, and the correlation coefficients and slopes of the regression curves were significantly different between the two types of subjects (P<0.05). Based on the results of this study, excessive contact pressure on the transducer should be avoided when detecting radial artery reflection waves in clinical practice. The results also show that the magnitude of the slope of the regression curve between the reflection parameters and the transducer contact pressure may be a potentially useful indicator for quantifying the elastic properties of the vessel.

Thiazole Imide-Based All-Acceptor Homopolymer with Branched Ethylene Glycol Side Chains for Organic Thermoelectrics.

n-Type semiconducting polymers with high thermoelectric performance remain challenging due to the scarcity of molecular design strategy, limiting their applications in organic thermoelectric (OTE) devices. Herein, we provide a new approach to enhance the OTE performance of n-doped polymers by introducing acceptor-acceptor (A-A) type backbone bearing branched ethylene glycol (EG) side chains. When doped with 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI), the A-A homopolymer PDTzTI-TEG exhibits n-type electrical conductivity (σ) up to 34 S cm-1 and power factor value of 15.7 µW m-1 K-2 . The OTE performance of PDTzTI-TEG is far greater than that of homopolymer PBTI-TEG (σ=0.27 S cm-1 ), indicating that introducing electron-deficient thiazole units in the backbone further improves the n-doping efficiency. These results demonstrate that developing A-A type polymers with EG side chains is an effective strategy to enhance n-type OTE performance.

Identification of DNA repair-related genes predicting pathogenesis and prognosis for liver cancer.

BACKGROUND: Liver cancer (LC) is one of the most fatal cancers throughout the world. More efficient and sensitive gene signatures that could accurately predict survival in LC patients are vitally needed to promote a better individualized and effective treatment. MATERIAL/METHODS: 422 LC and adjacent normal tissues with both RNA-Seq and clinical data in TCGA were embedded in our study. Gene set enrichment analysis (GSEA) was applied to identify genes and hallmark gene sets that are more valuable for liver cancer therapy. Cox regression analysis was used to identify genes related to overall survival (OS) and build the prediction model. cBioPortal database was used to examine the alterations of the panel mRNA signature. ROC curves and Kaplan-Meier curves were used to validate the prediction model. Besides, the expression of the genes in the model were validated using quantitative real-time PCR in clinical tissue specimens. RESULTS: The panel of DNA repair-related mRNA signature consisted of seven mRNAs: RFC4 (replication factor C subunit 4), ZWINT (ZW10 interacting kinetochore protein), UPF3B (UPF3B regulator of nonsense mediated mRNA decay), NCBP2 (nuclear cap binding protein subunit 2), ADA (adenosine deaminase), SF3A3 (splicing factor 3a subunit 3) and GTF2H1 (general transcription factor IIH subunit 1). On-line analysis of cBioPortal database found that the expression of the panel mRNA has a wide variation ranging from 7 to 10%. All the mRNAs were significantly upregulated in LC tissues compared to normal tissues (P < 0.05). The risk model is closely related to the OS of LC patients. The hazard ratio (HR) is 2.184 [95% CI (confidence interval) 1.523-3.132] and log-rank P-value < 0.0001. For clinical specimen validation, we found that all of the genes in the model upregulated in liver cancer tissues versus normal liver tissues, which was consistent with the results predicted. CONCLUSIONS: Our study demonstrated a mRNA signature including seven mRNA for prognosis prediction of LC. This panel gene signature provides a new criterion for accurate diagnosis and therapeutic target of LC.

A Simple Clinical Prediction Tool for COVID-19 in Primary Care with Epidemiology: Temperature-Leukocytes-CT Results.

BACKGROUND Effective identification of patients with suspected COVID-19 is vital for the management. This study aimed to establish a simple clinical prediction model for COVID-19 in primary care. MATERIAL AND METHODS We consecutively enrolled 60 confirmed cases and 152 suspected cases with COVID-19 into the study. The training cohort consisted of 30 confirmed and 78 suspected cases, whereas the validation cohort consisted of 30 confirmed and 74 suspected cases. Four clinical variables - epidemiological history (E), body temperature (T), leukocytes count (L), and chest computed tomography (C) - were collected to construct a preliminary prediction model (model A). By integerizing coefficients of model A, a clinical prediction model (model B) was constructed. Finally, the scores of each variable in model B were summed up to build the ETLC score. RESULTS The preliminary prediction model A was Logit (YA)=2.657X1+1.153X2+2.125X3+2.828X4-10.771, while the model B was Logit (YB)=2.5X1+1X2+2X3+3X4-10. No significant difference was found between the area under the curve (AUC) of model A (0.920, 95% CI: 0.875-0.953) and model B (0.919, 95% CI: 0.874-0.952) (Z=0.035, P=0.972). When ETLC score was more than or equal to 9.5, the sensitivity and specificity for COVID-19 was 76.7% (46/60) and 90.1% (137/152), respectively, and the positive and negative predictive values were 75.4% (46/61) and 90.7% (137/151), respectively. CONCLUSIONS The ETLC score is helpful for efficiently identifying patients with suspected COVID-19.

Synergistic effect of uniform lattice cation/anion doping to improve structural and electrochemical performance stability for Li-rich cathode materials.

There has been extensive research into lithium-rich layered oxide materials as candidates for the nextgeneration of cathode materials in lithium-ion batteries, due to their high energy density and low cost; however, their poor cycle life and fast voltage fade hinder their large-scale commercial application. Here, we propose a novel cation/anion (Na+/PO4 3-) co-doping approach to mitigate the discharge capacity and voltage fade of a Co-free Li1.2Ni0.2Mn0.6O2 cathode. Our results show that the synergistic effect of cation/anion doping can promote long cycle stability and rate performance by inhibiting the phase transformation of the layered structure to a spinel or rock-salt structure and stabilizing the well-ordered crystal structure during long cycles. The co-doped sample exhibits an outstanding cycle stability (capacity retention of 86.7% after 150 cycles at 1 C) and excellent rate performance (153 mAh g-1 at 5 C). The large ionic radius of Na+ can expand the Li slab to accelerate Li diffusion and the large tetrahedral PO4 3- polyanions with high electronegativity stabilize the local structure to improve the electrochemical performance.

Selecting the Best Elements from Previous Kidney Tumor Scoring Systems to Restructure Efficient Predictive Models for Surgery Type.

OBJECTIVE: The aim of this work was to select the best elements from previous scoring systems to restructure efficient predictive models for surgery type. METHODS: Sixteen elements were selected from 7 systems (RENAL, PADUA, DAP, ZS, NephRO, ABC, and CI). They were divided into 6 categories (tumor max. size, exophytic/endophytic, correlation with collecting system or sinus, tumor location, contact situation with the parenchyma, invasion depth). Three elements, selected from 3 different categories, were integrated to establish a total of 320 new models. According to AUC rank, optimized models were developed, and these models were divided into 3 sections. An analysis of the distribution of the 6 categories was made to explore the predictive capacities of the models. RESULTS: A total of 166 consecutive patients were included. Seventy-five patients underwent radical nephrectomy operations. The AUC of the 7 systems ranged from 0.81 to 0.844. Three optimized models (AUC 0.88) were developed to predict surgery type. These optimized models were composed of DAP (D), PADUA, (sinus), and ABC; DAP (D), RENAL (N), and ABC; NePhRO (O), PADUA (UCS), and ABC. Two categories ("exophytic/endophytic," p < 0.001; "correlation with collecting system or sinus," p = 0.001) were nonuniformly distributed. CONCLUSIONS: Seven systems held good predictive power for surgery type. Three optimized models were developed. "Correlation with collecting system or sinus" is a critical factor for predicting surgery type.

Deciphering an Abnormal Layered-Tunnel Heterostructure Induced by Chemical Substitution for the Sodium Oxide Cathode.

Demands for large-scale energy storage systems have driven the development of layered transition-metal oxide cathodes for room-temperature rechargeable sodium ion batteries (SIBs). Now, an abnormal layered-tunnel heterostructure Na0.44 Co0.1 Mn0.9 O2 cathode material induced by chemical element substitution is reported. By virtue of beneficial synergistic effects, this layered-tunnel electrode shows outstanding electrochemical performance in sodium half-cell system and excellent compatibility with hard carbon anode in sodium full-cell system. The underlying formation process, charge compensation mechanism, phase transition, and sodium-ion storage electrochemistry are clearly articulated and confirmed through combined analyses of in situ high-energy X-ray diffraction and ex situ X-ray absorption spectroscopy as well as operando X-ray diffraction. This crystal structure engineering regulation strategy offers a future outlook into advanced cathode materials for SIBs.

Deficiency of alkaline SMase enhances dextran sulfate sodium-induced colitis in mice with upregulation of autotaxin.

Intestinal alkaline SMase (Alk-SMase) cleaves phosphocholine from SM, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4- to 5-fold enhanced in Alk-SMase KO mice. Here, we further studied the pathogenesis of colitis induced by dextran sulfate sodium (DSS) in WT and KO mice. Compared with WT mice, KO mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury. Higher levels of PAF and lower levels of interleukin (IL)10 were identified in KO mice 2 days after DSS treatment. A greater and progressive increase of lysophosphatidic acid (LPA) was identified. The change was associated with increased autotaxin expression in both small intestine and colon, which was identified by immunohistochemistry study, Western blot, and sandwich ELISA. The upregulation of autotaxin coincided with an early increase of PAF. IL6 and TNFα were increased in both WT and KO mice. At the later stage (day 8), significant decreases in IL6, IL10, and PAF were identified, and the decreases were greater in KO mice. In conclusion, deficiency of Alk-SMase enhances DSS-induced colitis by mechanisms related to increased autotaxin expression and LPA formation. The early increase of PAF might be a trigger for such reactions.

A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis.

A new series of 20 brominated chalcone derivatives were designed, synthesized, and investigated for their effects against the growth of four cancer cell lines (EC109, SKNSH, HepG2, MGC803). Among them, compound 19 which given chemical name of H72, was the most potent one on gastric cancer cell lines (i.e. MGC803, HGC27, SGC7901) with IC50s ranged from 3.57 to 5.61µM. H72 exhibited less cytotoxicity to non-malignant gastric epithelial cells GES-1. H72 treatment of MGC803 and HGC27 induced generation of reactive oxygen species (ROS) leading to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. H72 also up-regulated the expression of DR5, DR4 and BimEL, and down-regulated the expression of Bid, Bcl-xL, and XIAP. N-acetyl cysteine (NAC), a ROS scavenger completely blocked these effects of H72 in MGC803 cells. Intraperitoneal administration of H72 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that H72 is a lead brominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer.

[Analgesic effect and safety of intercostal nerve cryoanalgesia after the video-assisted thoracoscopic surgery].

OBJECTIVE: To investigate the analgesic efficacy and safety of intercostal nerve cryoanalgesia after video-assisted thoracoscopic surgery (VATS). METHODS: This was a prospective randomized controlled study. From May 2014 to April 2015, 80 patients who would undergoing selective surgery performed by the same surgeon team were chosen, and were randomly divided into cryoanalgesia group and intravenous analgesia group by a random number table. Visual analogue scale (VAS) at resting and movement were measured on postoperative 4 h, 1 d, 2 d, 3 d, and the amount of supplemental morphine use and adverse reactions were recorded; plasma concentration of cortisol, blood glucose, C-reactive protein (CRP) and interleukin-6 (IL-6) were detected on preoperative and postoperative 4 h,1 d,2 d. RESULTS: Seventy-one patients with complete test process were included in the statistical analysis, including cryoanalgesia group (35 cases) and intravenous group (36 cases). No statistical differences were found in terms of age, gender, body mass index (BMI) between the two groups. VAS scores of cryoanalgesia group at movement on postoperative 4 h, 1 d, 2 d, 3 d were 5(5,7), 4(3,6), 3(3,4), 3(0,3), and in intravenous group were 5(5,6), 5(3,5), 3(3,4), 2(0,3), respectively, but there was no statistically different between two groups (P>0.05). Resting VAS scores of cryoanalgesia group on postoperative 4 h, 1 d, 2 d, 3 d were 3(2,4), 0(0,3), 0(0,0), 0(0,0), and in intravenous group were 3(0.5,4), 2(0,3), 0(0,1.5), 0(0,0) respectively, but there was no statistically different between two groups (P>0.05). Resting analgesic effectiveness (VAS≤5) of cryoanalgesia group were 91.4%, and in intravenous group were 97.2%, respectively. Median of morphine dosage was equal between two groups on postoperative 4 h, 1 d, 2 d, cumulative amount of morphine of cryoanalgesia group was higher than intravenous group, but the difference between the two groups was not statistically significant. Incidence of nausea and vomiting for intravenous group was 36.1%, significantly higher than cryoanalgesia group (17.1%, χ(2)=4.148, P<0.05). The change of plasma concentration of cortisol, C-response protein (CRP), interleuken-6(IL-6) was noticeable, but there was no statistical significance in each time point. CONCLUSION: The analgesic effect of both Intercostal nerve cryoanalgesia and intravenous analgesia after VATS is almost the same.Compare with intravenous analgesia, incidence of the adverse reactions of cryoanalgesia is lower, and there is no increasing in the stress response.

Effect of Preadministration of Nalmefene on Sufentanil-Induced Cough During Induction of General Anesthesia in Patients Undergoing Breast Surgery: A Double-Blind Randomized Controlled Trial.

Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 µg·kg-1 (Group LN), and high-dose nalmefene 0.25 µg·kg-1 (Group HN). Sufentanil 0.5 µg·kg-1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.