Predictive Value of a New Muscle Parameter in Patients with Resectable Gastric Cancer: A Pooled Analysis of Three Prospective Trials.

BACKGROUND: Sarcopenia is closely associated with gastric cancer (GC) prognosis. However, its exact definition remains controversial. METHODS: This study included computed tomography images and clinical data of patients from three prospective studies. The skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) were analyzed, and a new muscle parameter, skeletal muscle gauge (SMG), was obtained by multiplying the two parameters. The values of the three indices for predicting the prognosis of patients with GC were compared. RESULTS: The study included 717 patients. The findings showed median values of 42 cm2/m2 (range, 36.8-48.2 cm2/m2) for SMI, 45 HU (range, 41-49 HU) for SMRA, and 1842 (range, 1454-2260) for SMG. Postoperatively, 111 patients (15.5%) experienced complications. The 3-year overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were 74.3%, 68.2%, and 70%, respectively. Univariate logistic analysis showed that postoperative complications were associated with SMI (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.92-0.96), SMRA (OR, 0.87; 95% CI 0.84-0.90), and SMG (OR 0.99; 95% CI 0.98-0.99). After a two-step multivariate analysis, only SMG (OR 0.98, 95% CI 0.97-0.99) was an independent protective factor of postoperative complications. Multivariate analysis showed that SMG also was an independent protective factor of OS, DFS, and RFS. The patients were divided into low-SMG (L-SMG) group and high-SMG (H-SMG) groups. Chemotherapy benefit analysis of the patients with stage II low SMG showed that the OS, DFS, and RFS of the chemotherapy group were significantly better than those of the non-chemotherapy group (p < 0.05). CONCLUSION: The prospective large sample data showed that the new muscle parameter, SMG, can effectively predict the short-term outcome and long-term prognosis of patients with resectable gastric cancer. As a new muscle parameter index, SMG is worthy of further study.

Burden of gastroesophageal reflux disease in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of disease study 2019.

INTRODUCTION: For effective preventive strategies against GORD (gastro-esophageal reflux disease), we assessed the GORD burden from 1990 to 2019. METHODS: The burden of GORD between 1990 and 2019 was evaluated globally, regionally, and nationally. Using ASIR (age-standardized incidence), ASYLDs (age-standardized years lived with disabilitys), we compared them to the GBD world population per 100,000. The estimates were based on 95% uncertainty intervals (UIs). The AAPC (average annual percent change) in incidence, YLDs, along with prevalence rates with associated 95% CIs were estimated. RESULTS: Data to estimate the burden of GORD are scarce till now. The global ASIR of GORD in 2019 was 3792.79 per 100,000, an increase AAPC of 0.112% from 1990. The prevalence of GORD increased with a AAPC of 0.096% to 9574.45 per 100,000. Global ASYLDs in 2019 was 73.63, an increase AAPC of 0.105% from 1990. The GORD burden varies greatly depending on the development level and geographical location. USA demonstrated the most obvious decreasing trend in burden of GORD, while Sweden had an increasing trend. That the increase in GORD YLDs was mediated primarily by the growth and aging of population, was revealed by decomposition analyses. There was an inverse relationship between SDI (socio-demographic index) and GORD-burden. Frontier analyses revealed significant scope of improvement in the status of development at all levels. CONCLUSION: GORD is a public health challenge, especially in Latin America. Some SDI quintiles had declining rates, while some countries experienced increased rates. Thus, resources should be allocated for preventative measures based on country-specific estimates.

Dual-Role of Polyelectrolyte-Tethered Benzimidazolium Cation in Promoting CO2 /Pure Water Co-Electrolysis to Ethylene.

Electrochemical CO2 reduction reaction (CO2 RR), as a promising route to realize negative carbon emissions, is known to be strongly affected by electrolyte cations (i.e., cation effect). In contrast to the widely-studied alkali cations in liquid electrolytes, the effect of organic cations grafted on alkaline polyelectrolytes (APE) remains unexplored, although APE has already become an essential component of CO2 electrolyzers. Herein, by studying the organic cation effect on CO2 RR, we find that benzimidazolium cation (Beim+ ) significantly outperforms other commonly-used nitrogenous cations (R4 N+ ) in promoting C2+ (mainly C2 H4 ) production over copper electrode. Cyclic voltammetry and in situ spectroscopy studies reveal that the Beim+ can synergistically boost the CO2 to *CO conversion and reduce the proton supply at the electrocatalytic interface, thus facilitating the *CO dimerization toward C2+ formation. By utilizing the homemade APE ionomer, we further realize efficient C2 H4 production at an industrial-scale current density of 331 mA cm-2 from CO2 /pure water co-electrolysis, thanks to the dual-role of Beim+ in synergistic catalysis and ionic conduction. This study provides a new avenue to boost CO2 RR through the structural design of polyelectrolytes.

Release of endogenous hydrogen sulfide in enteric nerve cells suppresses intestinal motility during severe acute pancreatitis.

Previous studies have shown that during severe acute pancreatitis (SAP) attacks, hydrogen sulfide (H2S) is released in the colon. However, the roles played by H2S in regulating enteric nerves remain unclear. In this study, we examined the association between SAP-induced H2S release and loss of intestinal motility, and also explored the relevant mechanism in enteric nerve cells. A rat SAP model was constructed and enteric nerve cells were prepared. Intestinal mobility was evaluated by measuring the number of bowel movements at indicated time points and by performing intestinal propulsion tests. The production of inflammatory cytokines during a SAP attack was quantified by ELISA, and the levels of cystathionine-γ-lyase (CSE) and cystathionine-ß-synthase (CBS) were examined by immunohistochemistry and western blot analysis. In vivo studies showed that PI3K/Akt/Sp1 signaling in enteric nerve cells was blocked, confirming the mechanism of endogenous H2S formation by western blot analysis and immunofluorescence. Our results also showed that rats with SAP symptoms had reduced intestinal motility. Furthermore, PI3K/Akt/Sp1 signaling was triggered and CSE expression was up-regulated, and these changes were associated with H2S formation in the colon. In addition, propargylglycine reduced the levels of inflammatory cytokines and suppressed the release of H2S. Enteric nerve cells that were incubated with LY294002 and transfected with a Sp1-knockdown vector displayed decreased levels of CSE production, which led to a decrease in H2S production. These results suggest that SAP symptoms suppressed the intestinal motility of rats via the release of H2S in enteric nerve cells, which was dependent on the inflammation-induced PI3K/Akt/Sp1 signaling pathway.

Report: Small cell neuroendocrine carcinoma (SCNEC) of the tongue: A case report.

Small cell neuroendocrine carcinoma (SCNEC) of the tongue is very rare. We here present a SCNEC impatient with distant metastasis. A 74-year-old Chinese male went to hospital to treat a tongue tumor, which was founded at a conventional physical examination in Weifang Stomatology Hospital. The check of positron emission tomography-computer tomography (PET-CT) by Weifang people's hospital revealed a tumor in the right root of tongue, and distant metastasis in the right submandibular area, neck, mediastinum, right hilar, abdominal, retroperitoneal multiple lymph nodes, left thyroid, right lower lung, right scapula and bilateral adrenal. The patient was diagnosed tongue SCNEC by the pathological analysis of the tissue section. Conforming to the diagnosis of tongue SCNEC, the patient received adjuvant chemotherapy for 6 cycles with etoposide and carboplatin, and is alive now 9 months after the diagnosis.

Investigation in image quality and immediate patient safety using pre-dual-flow injection for low-contrast dose spectral pulmonary artery CT angiography.

Purpose: The patient safety of iodine contrast-enhanced pulmonary artery CT angiography (CTPA) is widely concerned. This study aimed to investigate the image quality and immediate patient safety of spectral CTPA using a lower-contrast dose pre-dual-flow injection method. Methods: This retrospective study included 120 patients with suspected pulmonary embolisms who received spectral CTPA between February and December 2022. Patients were divided into normal contrast injection (Group A, n=60) and pre-dual-flow group (Group B, n=60). CT values of pulmonary arteries (PAs) at different levels, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), arteriovenous separation performance, and beam hardening artifact (BHA) index of two sets of images were measured or calculated. The subjective image quality and immediate patient safety were also scored using the three-point method. Results: Group B had a contrast dose reduction by 42.5 % (60 vs. 34.5 mL). Radiation exposure dose was not statistically different between the two groups (P>0.05). CT values of different-level PAs on group B images were higher than those on group A images (P<0.05). Group B images had higher SNR and CNR, better arteriovenous separation between PA trunk and pulmonary vein, and lower BHA index on soft tissue and PA (all P<0.05). For subjective evaluation of image quality, group B had a better score in beam hardening artifact (P<0.05). For immediate patient safety, the score in comfortability was statistically higher in group B, with P<0.05. Conclusions: Comparing with the normal injection method, pre-dual-flow spectral CTPA with a lower contrast dose injected results in better image quality and shows potential in patient-safety promotion.

Gigantol ameliorates DSS-induced colitis via suppressing ß2 integrin mediated adhesion and chemotaxis of macrophage.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium, recognized as "Shihu" in traditional Chinese medicine, holds a rich history of medicinal utilization documented in the Chinese Pharmacopoeia. Ancient texts like "Shen Nong Ben Cao Jing" extol Dendrobium's virtues as a superior herbal medicine fortifying "Yin" and invigorating the five viscera. Dendrobium is extensively employed for the treatment of gastrointestinal inflammatory disorders, showcasing significant therapeutic efficacy, particularly against ulcerative colitis (UC), within the realm of Chinese ethnopharmacology. Dendrobium plays crucial pharmacological roles due to its rich content of polysaccharides, alkaloids, phenanthrenes, and bibenzyls. Gigantol, a prominent bibenzyl compound, stands out as one of the most vital active constituents within Dendrobium, the gigantol content of Dendrobium leaves can reach approximately 4.79 µg/g. Its significance lies in being recognized as a noteworthy anti-inflammatory compound derived from Dendrobium. AIM OF THE STUDY: Given the pivotal role of gigantol as a primary active substance in Dendrobium, the therapeutic potential of gigantol for gastrointestinal diseases remains enigmatic. Our present investigation aimed to evaluate the therapeutic effects of gigantol on dextran sulfate sodium (DSS)-induced colitis and reveal its potential mechanism in countering UC activity. MATERIALS AND METHODS: The protective efficacy of gigantol against colitis was assessed by examining the histopathological changes and conducting biochemical analyses of colon from DSS-challenged mice. Assessments focused on gigantol's impact on improving the intestinal epithelial barrier and its anti-inflammatory effects in colonic tissues of colitis mice. Investigative techniques included the exploration of the macrophage inflammatory signaling pathway via qPCR and Western blot analyses. In vitro studies scrutinized macrophage adhesion, migration, and chemotaxis utilizing transwell and Zigmond chambers. Furthermore, F-actin and Rac1 activation assays detailed cellular cytoskeletal remodeling. The potential therapeutic target of gigantol was identified and validated through protein binding analysis, competitive enzyme-linked immunosorbent assay (ELISA), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay. The binding sites between gigantol and its target were predicted via molecular docking. RESULTS: Gigantol ameliorated symptoms of DSS-induced colitis, rectified damage to the intestinal barrier, and suppressed the production of pro-inflammatory cytokines in colonic tissues. Intriguingly, gigantol significantly curtailed NF-κB signaling activation in the colons of DSS-induced colitis mice. Notably, gigantol impaired the ß2 integrin-dependent adhesion and migratory capacity of RAW264.7 cells. Moreover, gigantol notably influenced the cytoskeleton remodeling of RAW264.7 cells by suppressing Vav1 phosphorylation and Rac1 activation. Mechanistically, gigantol interacted with ß2 integrin, subsequently diminishing binding affinity with intercellular adhesion molecule-1 (ICAM-1). CONCLUSIONS: In conclusion, these findings elucidate that gigantol ameliorates DSS-induced colitis by antagonizing ß2 integrin-mediated macrophage adhesion, migration, and chemotaxis, thus it may impede macrophage recruitment and infiltration into colonic tissues. This study suggests that gigantol shows promise as a viable candidate for clinical colitis therapy.

Geniposide ameliorates dextran sulfate sodium-induced ulcerative colitis via KEAP1-Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried fruit of Gardenia jasminoides Ellis (Zhizi in Chinese) is a traditional medicine used for thousands of years in China, Japan and Korea. Zhizi was recorded in Shennong Herbal, as a folk medicine, it reduces fever and treats gastrointestinal disturbance with antiphlogistic effects. Geniposide, an iridoid glycoside, is an important bioactive compound derived from Zhizi and possesses remarkable antioxidant and anti-inflammatory capacities. The pharmacological efficacy of Zhizi is highly related to the antioxidant and anti-inflammatory effects of geniposide. AIM OF THE STUDY: Ulcerative colitis (UC) is a common chronic gastrointestinal disease as a global public health threat. Redox imbalance is an essential factor in the progression and recurrence of UC. This study aimed to explore the therapeutic effect of geniposide on colitis and uncover the underlying mechanisms of geniposide-mediated antioxidant and anti-inflammatory activities. EXPERIMENTAL DESIGN: The study design involved investigating the novel mechanism by which geniposide ameliorates dextran sulfate sodium (DSS)-induced colitis in vivo and lipopolysaccharide (LPS)-challenged colonic epithelial cells in vitro. MATERIALS AND METHODS: The protective effect of geniposide against colitis was evaluated by histopathologic observation and biochemical analysis of colonic tissues in DSS-induced colitis mice. The antioxidant and anti-inflammatory effects of geniposide were evaluated in both DSS-induced colitis mice and LPS-challenged colonic epithelial cells. Immunoprecipitation, drug affinity responsive target stability (DARTS), and molecular docking were performed to identify the potential therapeutic target of geniposide and the potential binding sites and patterns. RESULTS: Geniposide ameliorated the symptoms of DSS-induced colitis and colonic barrier injury, inhibited pro-inflammatory cytokine expression, and suppressed activation of the NF-κB signaling in colonic tissues of DSS-challenged mice. Geniposide also ameliorated lipid peroxidation and restored redox homeostasis in DSS-treated colonic tissues. In addition, in vitro experiments also showed that geniposide exhibited significant anti-inflammatory and antioxidant activity, as evidenced by suppressed IκB-α and p65 phosphorylation and IκB-α degradation, and enhanced the phosphorylation and transcriptional activity of Nrf2 in LPS-treated Caco2 cells. ML385, a specific Nrf2 inhibitor, abolished the protective effect of geniposide against LPS-induced inflammation. Mechanistically, geniposide could bind to KEAP1, thereby disrupting the interaction between KEAP1 and Nrf2, preventing Nrf2 from degradation and activating the Nrf2/ARE signaling pathway, ultimately suppressing the onset of inflammation caused by redox imbalance. CONCLUSIONS: Geniposide ameliorates colitis by activation of Nrf2/ARE signaling, while preventing colonic redox imbalance and inflammatory damage, indicating that geniposide can be considered as a promising lead compound for the treatment of colitis.

Luteolin ameliorates DSS-induced colitis in mice via suppressing macrophage activation and chemotaxis.

OBJECTIVES: Luteolin, known for its multifaceted therapeutic properties against inflammatory diseases, holds potential for addressing the unmet need for effective treatments in ulcerative colitis (UC), a prevalent subtype of inflammatory bowel disease (IBD). This study aimed to comprehensively assess luteolin's therapeutic efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model, shedding light on its anti-UC mechanisms. METHODS: Our investigation encompassed in vivo assessments of luteolin's therapeutic potential against DSS-induced colitis through rigorous histopathological examination and biochemical analyses. Furthermore, we scrutinized luteolin's anti-inflammatory prowess in vitro using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary peritoneal macrophages. Additionally, we quantitatively evaluated the impact of luteolin on C-C motif chemokine ligand 2 (CCL2)-induced macrophage migration employing Transwell and Zigmond chambers. Furthermore, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and molecular docking were employed to identify potential therapeutic targets of luteolin and investigate their binding sites and interaction patterns. RESULTS: Luteolin demonstrated therapeutic potential against DSS-induced colitis by ameliorating colitis symptoms, restoring intestinal barrier integrity, and inhibiting proinflammatory cytokine production in the colonic tissues. Moreover, luteolin demonstrated robust anti-inflammatory activity in vitro, in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary peritoneal macrophages. Notably, luteolin suppressed the phosphorylation of IKKα/ß, IκBα, and p65, along with preventing IκBα degradation in LPS-treated RAW264.7 cells and peritoneal macrophages. Furthermore, luteolin impaired the migratory behavior of RAW264.7 cells and peritoneal macrophages, as evidenced by reduced migration distance and velocity of luteolin-treated macrophages. Mechanistically, luteolin was found to antagonize IKKα/ß, subsequently inhibiting IKKα/ß phosphorylation and the activation of NF-κB signaling. CONCLUSION: Luteolin emerges as a promising lead compound for the clinical therapy of colitis by virtue of its ability to ameliorate DSS-induced colitis, antagonize IKKα/ß, suppress NF-κB signaling, and impede macrophage activation and migration.

Mg-protoporphyrin, haem and sugar signals double cellular total RNA against herbicide and high-light-derived oxidative stress.

Cellular total RNA level is usually stable, although it may increase gradually during growth or seed germination, or decrease gradually under environmental stresses. However, we found that plant cell RNA could be doubled within 48 h in response to herbicide-induced Mg-protoporphyrin and heme accumulation or a high level of sugar treatment. This rapid RNA multiplication is important for effective cellular resistance to oxidative stress, such as high-light and herbicide co-stress conditions, where the plastid-signalling defective mutant gun1 shows an apparent phenotype (more severe photobleaching). Hexokinase is required for sugar-induced RNA multiplication. While both sugar and Mg-protoporphyrin IX require plastid protein GUN1 and a nuclear transcription factor ABI4, haem appears to function through an independent pathway to control RNA multiplication. The transcription co-factor CAAT binding protein mediates the rapid RNA multiplication in plant cells in all the cases.

Heat Transfer Scale Effect Analysis and Parameter Measurement of an Electrothermal Microgripper.

An electrothermal microgripper is an important actuator in microelectromechanical and micro-operating systems, and its temperature field analysis is the core problem in research and design. Because of the small size of an electrothermal microgripper, its microscale heat transfer characteristics are different from those of the macrostate. At present, only a few studies on the heat transfer scale effect in electrothermal microgrippers have been conducted, and the heat transfer analysis method under the macrostate is often used directly. The temperature field analysed and simulated is different from the actual situation. In the present study, the heat transfer mechanism of an electrothermal microgripper in the microscale was analysed. The temperature field of a series of microscale heating devices was measured using microthermal imaging equipment, and the heat transfer parameters of the microscale were fitted. Results show that the natural convective heat transfer coefficient of air on the microscale can reach 60-300 times that on the macroscale, which is an important heat transfer mode affecting the temperature field distribution of the electrothermal microgripper. Combined with the finite element simulation software, the temperature field of the electrothermal microgripper could be accurately simulated using the experimental microscale heat transfer parameters measured. This study provides an important theoretical basis and data support for the optimal design of the temperature controller of the electrothermal microgripper.

Brassinosteroids counteract abscisic acid in germination and growth of Arabidopsis.

Brassinosteroids (BRs) are involved in multiple plant growth and development processes, such as cell elongation, photomorphogenesis, flowering time control, and stress responses. The phytohormone abscisic acid (ABA) is crucial to plant development and adaptation to stressful environments. The receptors and pathways of BRs and ABA have been deeply studied. But the relationship between them remained largely unknown and there are only few reports about it. Our experiments showed that the BR-deficient and BR-insensitive Arabidopsis mutants det2, bri1-5 and bri1-9 were more sensitive to ABA than the wild type (Ws-2), especially the det2 and bri1-9 mutants. Germination, hypocotyl and root elongation, and stomatal apertures of the mutants were more severely inhibited by ABA. All the results suggest that BRs counteract ABA in regulating plant growth, and the interaction may be complicated. The possible mechanisms are discussed.

Lack of salicylic acid in Arabidopsis protects plants against moderate salt stress.

Previous studies showed that salicylic acid (SA)-deficient transgenic Arabidopsis expressing the salicylate hydroxylase gene NahG had a higher tolerance to moderate salt stress. SA may potentiate the stress response of germination and growth of Arabidopsis seedlings by inducing reactive oxygen species (ROS). However, the detailed mechanism for a better adaption of NahG plants to moderate salt stress is largely unknown. In the present study we found that a higher GSH/GSSG (glutathione/oxidized glutathione) ratio and ASA/DHA (ascorbic acid/dehydroascorbate) ratio in NahG plants during the stress may be the key reason for their stress-tolerance advantage. NahG plants actually could not produce more active antioxidant enzymes than the wild-type ones under natural conditions, but maintain higher activities of glutathione reductase (GR) and dehydroascorbate reductase (DHAR) during the stress. Hereby, the reduced glutathione and reduced ascorbic acid contents are higher in NahG plants under salt stress. However, NahG plants do not adapt better under severe salt stress. All antioxidant enzyme activities, GSH/GSSG ratio and ASA/DHA ratio declined substantively at 400 mM NaCl stress in both NahG and wild-type seedlings.

Catalyst-free electrochemical decarboxylative cross-coupling of N-hydroxyphthalimide esters and N-heteroarenes towards C(sp3)-C(sp2) bond formation.

Cheap and widely available carboxylic acids are a class of ideal substrates to construct valuable compounds. As a candidate of decarboxylative reactions, the acid-based neutral N-hydroxyphthalimide ester undergoes a reductive decarboxylative process rather than a common oxidative decarboxylative process, which is a potential transformation mode for new reactions. In this work, we developed an electrochemical C(sp3)-C(sp2) coupling of N-hydroxyphthalimide esters and N-heteroarenes without any catalysts. Remarkably, this electrochemical protocol can not only be directly realised by carboxylic acids in a one-pot fashion, but also be scaled up using a continuous-flow reactor.

[Effects of bone morphogenetic protein-2 on proliferation of tongue cancer Tca8113].

OBJECTIVE: To investigate the morphology and proliferation effects of adenovirus containing bone morphogenetic protein-2(BMP-2) on tongue cancer Tca8113 cells. METHODS: Tca8113 cells were transfected with the Ad-BMP-2 of 0, 50, 100 multiplicity of infection (MOI) respectively. Inverted fluorescence microscope was used to evaluate the morphological changes of these cells. Western blot analysis was performed to determine the expression levels of BMP-2 in the transfected cells. Methyl thiazolyl tetrazolium (MTT) assay was performed to monitor the proliferative activity of the infected Tca8113 cells and then the growth curve was made. RESULTS: The transfection efficiency reached the highest when the MOI was 100. Moreover, the expression of BMP-2 was detected in Tca8113 cells by Western blot. There were no obvious morphological changes of the Tca8113 cells before and after transfection. And the proliferation of transfected Tca8113 cells decreased compared with control. CONCLUSION: Ad-BMP-2 gene can inhibit the proliferation of Tca8113 cells in vitro.

[Effects of tumor necrosis factor-alpha on the growth of rat osteoblasts].

OBJECTIVE: To investigate the effects of tumor necrosis factor alpha (TNF-alpha) on the growth of rat osteoblasts. To find out the mechanisms that TNF-alpha regulates the growth of osteoblasts. METHODS: To assay osteoblasts proliferation by MTT. To assay alkaline phosphatase (ALP) activity of osteoblasts by PP-nitrophenyl phosphate (PNPP). RESULTS: The osteblasts proliferation and the ALP activity decreased in treatment groups, and the significantly lower levels were observed in above 50 ng/mL groups (P<0.05). CONCLUSION: TNF-alpha restrained osteoblasts proliferation and differentiation, and the effects were more significant in above 50 ng/mL groups.