OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3ß/ß-catenin pathway.

BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

ALDH2 rs671 and MTHFR rs1801133 polymorphisms are risk factors for arteriosclerosis in multiple arteries.

BACKGROUND: Arteriosclerosis in multiple arteries has long been associated with heightened cardiovascular risk. Acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) play an important role in the pathogenesis of arteriosclerosis by participating in the oxidation and reduction reactions in vascular endothelial cells. The purpose was to investigate the relationship of ALDH2 and MTHFR gene polymorphisms with arteriosclerosis in multiple arteries. METHODS: 410 patients with arteriosclerosis in single artery and 472 patients with arteriosclerosis in multiple arteries were included. The relationship between ALDH2 rs671 and MTHFR rs1801133 polymorphisms and arteriosclerosis in single artery and arteriosclerosis in multiple arteries was analyzed. RESULTS: The proportion of ALDH2 rs671 A allele (35.6% vs. 30.9%, P = 0.038) and MTHFR rs1801133 T allele (32.6% vs. 27.1%, P = 0.012) in patients with arteriosclerosis in multiple arteries was significantly higher than that in arteriosclerosis in single artery, respectively. The proportion of history of alcohol consumption in patients with ALDH2 rs671 G/G genotype was higher than those in ALDH2 rs671 G/A genotype and A/A genotype (P < 0.001). The results of logistic regression analysis indicated that ALDH2 rs671 A/A genotype (A/A vs. G/G: OR 1.996, 95% CI: 1.258-3.166, P = 0.003) and MTHFR rs1801133 T/T genotype (T/T vs. C/C: OR 1.943, 95% CI: 1.179-3.203, P = 0.009) may be independent risk factors for arteriosclerosis in multiple arteries (adjusted for age, sex, smoking, drinking, hypertension, and diabetes). CONCLUSIONS: ALDH2 rs671 A/A and MTHFR rs1801133 T/T genotypes may be independent risk factors for arteriosclerosis in multiple arteries.

Utility of Artificial Intelligence for Real-Time Anatomical Landmark Identification in Ultrasound-Guided Thoracic Paravertebral Block.

Thoracic paravertebral block (TPVB) is a common method of inducing perioperative analgesia in thoracic and abdominal surgery. Identifying anatomical structures in ultrasound images is very important especially for inexperienced anesthesiologists who are unfamiliar with the anatomy. Therefore, our aim was to develop an artificial neural network (ANN) to automatically identify (in real-time) anatomical structures in ultrasound images of TPVB. This study is a retrospective study using ultrasound scans (both video and standard still images) that we acquired. We marked the contours of the paravertebral space (PVS), lung, and bone in the TPVB ultrasound image. Based on the labeled ultrasound images, we used the U-net framework to train and create an ANN that enabled real-time identification of important anatomical structures in ultrasound images. A total of 742 ultrasound images were acquired and labeled in this study. In this ANN, the Intersection over Union (IoU) and Dice similarity coefficient (DSC or Dice coefficient) of the paravertebral space (PVS) were 0.75 and 0.86, respectively, the IoU and DSC of the lung were 0.85 and 0.92, respectively, and the IoU and DSC of the bone were 0.69 and 0.83, respectively. The accuracies of the PVS, lung, and bone were 91.7%, 95.4%, and 74.3%, respectively. For tenfold cross validation, the median interquartile range for PVS IoU and DSC was 0.773 and 0.87, respectively. There was no significant difference in the scores for the PVS, lung, and bone between the two anesthesiologists. We developed an ANN for the real-time automatic identification of thoracic paravertebral anatomy. The performance of the ANN was highly satisfactory. We conclude that AI has good prospects for use in TPVB. Clinical registration number: ChiCTR2200058470 (URL: http://www.chictr.org.cn/showproj.aspx?proj=152839 ; registration date: 2022-04-09).

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study.

BACKGROUND: Genetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population. METHODS: The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. RESULTS: The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P < 0.001), and CYP2C19*2 allele (33.8% vs. 25.7%, P < 0.001) in hypertension group was significantly higher than that in control group. Multivariate logistic regression (adjusted for gender, age, smoking, and drinking) indicated that CYP2C19 *1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And the CYP2C19 IM genotype (IM vs. EM: OR 1.514, 95% CI: 1.291-1.775, P < 0.001), PM genotype (PM vs. EM: OR 2.120, 95% CI: 1.638-2.743, P < 0.001), IM + PM genotypes (IM + PM vs. EM: OR 1.617, 95% CI: 1.390-1.882, P < 0.001) may increase risk of hypertension. CONCLUSIONS: CYP2C19 loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes include CYP2C19 *1/*2, *1/*3, and *2/*2.

Chlorogenic acid enhances alveolar macrophages phagocytosis in acute respiratory distress syndrome by activating G protein-coupled receptor 37 (GPR 37).

BACKGROUND: Impaired alveolar macrophages phagocytosis can contribute to pathogenesis of acute respiratory distress syndrome (ARDS) and negatively impacts clinical outcomes. Chlorogenic acid (CGA) is a naturally occurring polyphenolic compound with potential anti-inflammatory and antioxidant bioactivities. Studies have shown that CGA plays a protective role in ARDS, however, the precise protective mechanism of CGA against ARDS, is still unclear. PURPOSE: The aim of this study was to investigate whether CGA enhances alveolar macrophages phagocytosis to attenuate lung injury during ARDS. METHODS: RAW264.7 cells were stimulated with lipopolysaccharides (100 µg/ml for 24 h) and treated with CGA (100, 200, and 400 µM CGA for 1 h) to measure pro-inflammatory cytokine levels, GPR37 expression and macrophages phagocytosis. Mouse models of ARDS induced by cecal ligation and perforation (CLP) surgery were treated with CGA (100 or 200 mg/kg) to investigate lung inflammatory injury and alveolar macrophages phagocytosis. Computational modeling was performed to examine potential binding sites of G protein-coupled receptor 37 (GPR37) with CGA, and the results were validated by interfering with the binding sites. RESULT: In vitro, CGA notably ameliorated inflammatory response and increased phagocytosis in lipopolysaccharides-induced RAW264.7 cells. In vivo, CGA administration significantly alleviated lung inflammatory injury, decreased the bacteria load in the lung, promoted alveolar macrophages phagocytosis and improved the survival rate in mice with CLP-induced ARDS. Moreover, CGA markedly upregulated the expression of GPR37 in vivo and in vitro. However, the protective effect of CGA against ARDS were reversed after silencing the expression of GPR37. CONCLUSION: CGA has a protective effect against ARDS and may enhance alveolar macrophages phagocytosis and attenuate lung inflammatory injury by upregulating GPR37 expression.

Physiological and Molecular Changes in Cherry Red Tobacco in Response to Iron Deficiency Stress.

The genotype CR60 is a spontaneous Cherry Red variant (containing granular red dapples on flue-cured leaves) of the Yunyan 87 (Y87) tobacco; it accumulates higher concentration of iron (Fe) in leaves than Y87, but the physiological differences between them remain largely unknown. We investigated the physiological and molecular mechanisms of CR60 in response to Fe deficiency under hydroponic conditions. Our results showed no significant phenotypic difference between Y87 and CR60 at optimal (40 µM) and high Fe (160 and 320 µM) concentrations. By contrast, CR60 exhibited higher tolerance to Fe deficiency (0 µM) than Y87, as shown by higher concentrations of chlorophyll in CR60 leaves after 21-day Fe-deficiency stress. Transcriptome profiling coupled with RT-PCR analyses found that the expression of IRT1 and several genes associated with chlorophyll biosynthesis and photosynthesis (e.g., PRO, GSA, FD1, PsbO, and PC) was higher in CR60 than Y87. These results indicated that CR60 maintains sufficient Fe uptake, chlorophyll biosynthesis and photosynthetic rate when subjected to Fe starvation.

Effects of erector spinae plane block and retrolaminar block on analgesia for multiple rib fractures: a randomized, double-blinded clinical trial.

OBJECTIVE: To investigate the effects of Erector Spinae Plane Block (ESPB) and Retrolaminar Block (RLB) on intra- and postoperative analgesia in patients with Multiple Rib Fractures (MRFs). METHODS: A total of 80 MRFs patients were randomly divided into the ESPB (Group E) and RLB (Group R) groups. After general anesthesia, ESPB and RLB were performed under ultrasound guidance, respectively, together with 20 mL of 0.5% ropivacaine and Patient-Controlled Intravenous Analgesia (PCIA). RESULTS: Thirty-four cases in Group E and 33,cases in Group R showed unclear paravertebral spaces. The intraoperative dosage of remifentanil (mean ± SD) (392.8 ± 118.7 vs. 501.7 ± 190.0 µg) and postoperative morphine PCIA dosage, (7.35 ± 1.55 vs. 14.73 ± 2.18 mg) in Group R were significantly less than those in Group E; the Visual Analog Scale (VAS) scores in Group R at 2 (2.7 ± 1.2 vs. 3.4 ± 1.4), 4 (2.2 ± 1.1 vs. 2.8 ± 0.9), 12 (2.5 ± 0.9 vs. 3.0 ± 0.8), and 24 hours (2.6 ± 1.0 vs. 3.1 ± 0.9) after surgery were significantly lower than those in Group E. Finally, the normal respiratory diaphragm activity (2.17 ± 0.22 vs. 2.05 ± 0.19), pH (median [IQR] (7.38 [7.31-7.45] vs. 7.36 [7.30-7.42]), and partial pressure of carbon dioxide (PaCO2) (44 [35-49] vs. 42.5 [30-46]) after the operation in Group R were significantly better than those in Group E (p < 0.05). CONCLUSIONS: RLB was a more effective analgesic method than ESPB in the treatment of MRF.

Carvacrol delays Phomopsis stem-end rot development in pummelo fruit in relation to maintaining energy status and antioxidant system.

Pummelo fruit rapidly depreciate in commodity value due to postharvest fungal decay and fruit quality deterioration. Here, we used carvacrol (CVR) to control Phomopsis stem-end rot (SER) caused by Diaporthe citri in pummelo fruit stored at 25 °C. Antifungal activity of CVR inhibited D. citri growth and Phomopsis SER development. Harvested pummelo fruit treated with CVR delayed firmness loss and lowered electrolyte leakage, and retarded hydrogen peroxide (H2O2) and malondialdehyde (MDA) accumulation. Unlike the control fruit, the CVR-treated fruit maintained higher levels of adenosine triphosphate and energy charge, and increased ATPase, succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and cytochrome C oxidase (CCO) activities, along with up-regulated expression levels of the respective genes. CVR improved the antioxidant capacity, as evidenced by higher non-enzymatic antioxidants amounts, higher activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX) and glutathione reductase (GR), and up-regulated expression levels of ROS-scavenging-related genes. Collectively, CVR treatment maintained the energy status and antioxidant capacity in D. citri-infected pummelo fruit, which revealed antifungal mechanisms critical for controlling postharvest fungal diseases.

The Antifungal Activity of Loquat (Eriobotrya japonica Lindl.) Leaves Extract Against Penicillium digitatum.

This study was performed to determine the antifungal activity of loquat (Eriobotrya japonica Lindl) leaf extract (LLE) against the citrus postharvest pathogen Penicillium digitatum (P. digitatum). The LLE exhibited an antifungal activity against P. digitatum, with a minimum inhibitory concentration (MIC) of 0.625 mg/ml and a minimum fungicidal concentration (MFC) of 1.25 mg/ml. Significant inhibitory effects of LLE on mycelial growth and spore germination of P. digitatum were seen in a dose-dependent manner. Simultaneously, to investigate possible antifungal mechanisms by LLE, we analyzed their influence on morphological changes, cell membrane permeability, cell wall and cell membrane integrity, and adenosine phosphates (ATP, ADP, and AMP) levels. Alterations, such as sunken surface and malformation, occurred in the LLE-treated P. digitatum spores. Furthermore, intracellular inclusion content decreased after LLE treatment, indicating an increase in cell membrane permeability. Besides, the LLE treatment induced a significant decline in the level of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) with a noticeable addition of extracellular ATP, ADP, and AMP during the entire treatment period. Overall, the results manifested that the antifungal activity of LLE against P. digitatum can be attributed to the derangement of cell membrane permeability and disordered energy metabolism. This is the first report on the mechanism of antifungal activity of LLE and could be useful in the development of targeted fungicides from natural origin.

Effects of general versus subarachnoid anaesthesia on circadian melatonin rhythm and postoperative delirium in elderly patients undergoing hip fracture surgery: A prospective cohort clinical trial.

BACKGROUND: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome). METHODS: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence. FINDINGS: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020). INTERPRETATION: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences. FUNDING: The study was supported by the National Natural Science Foundation of China (81971012, 81873726, 81901095, 81701052, and 81801070), Key Clinical Projects of Peking University Third Hospital (BYSYZD2019027), and Peking University "Clinical Medicine plus X" Youth Project (PKU2020LCXQ016).

Genipin Attenuates Tau Phosphorylation and Aß Levels in Cellular Models of Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating brain disorder characterized by neurofibrillary tangles and amyloid plaques. Inhibiting Tau protein and amyloid-beta (Aß) production or removing these molecules is considered potential therapeutic strategies for AD. Genipin is an aglycone and is isolated from the extract of Gardenia jasminoides Ellis fruit. In this study, the effect and molecular mechanisms of genipin on the inhibition of Tau aggregation and Aß generation were investigated. The results showed that genipin bound to Tau and protected against heparin-induced Tau fibril formation. Moreover, genipin suppressed Tau phosphorylation probably by downregulating the expression of CDK5 and GSK-3ß, and activated mTOR-dependent autophagy via the SIRT1/LKB1/AMPK signaling pathway in Tau-overexpressing cells. In addition, genipin decreased Aß production by inhibiting BACE1 expression through the PERK/eIF2α signaling pathway in N2a/SweAPP cells. These data indicated that genipin could effectively lead to a significant reduction of phosphorylated Tau level and Aß generation in vitro, suggesting that genipin might be developed into an effective therapeutic complement or a potential nutraceutical for preventing AD.

mascRNA and its parent lncRNA MALAT1 promote proliferation and metastasis of hepatocellular carcinoma cells by activating ERK/MAPK signaling pathway.

MALAT1-associated small cytoplasmic RNA (mascRNA) is a cytoplasmic tRNA-like small RNA derived from nucleus-located long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). While MALAT1 was extensively studied and was found to function in multiple cellular processes, including tumorigenesis and tumor progression, the role of mascRNA was largely unknown. Here we show that mascRNA is upregulated in multiple cancer cell lines and hepatocellular carcinoma (HCC) clinical samples. Using HCC cells as model, we found that mascRNA and its parent lncRNA MALAT1 can both promote cell proliferation, migration, and invasion in vitro. Correspondingly, both of them can enhance the tumor growth in mice subcutaneous tumor model and can promote metastasis by tail intravenous injection of HCC cells. Furthermore, we revealed that mascRNA and MALAT1 can both activate ERK/MAPK signaling pathway, which regulates metastasis-related genes and may contribute to the aggressive phenotype of HCC cells. Our results indicate a coordination in function and mechanism of mascRNA and MALAT1 during development and progress of HCC, and provide a paradigm for deciphering tRNA-like structures and their parent transcripts in mammalian cells.

Anti-inflammatory effects of curcumin in acute lung injury: In vivo and in vitro experimental model studies.

Inflammation plays a major role in the pathogenesis of acute lung injury (ALI), but the mechanism remains unclear. Current anti-inflammatory therapy has poor efficacy on ALI. The aim of this study was to investigate the protective mechanism of curcumin against ALI. In in vivo experiments, curcumin significantly alleviated lung inflammation, histopathological injury and MPO activity, serum concentrations of CCL7, IL-6 and TNF-α, and mortality in mice compared to the model group. RAW264.7 cells cultured in the presence of lipopolysaccharide and adenosine triphosphate showed significantly lower viability, higher pyroptotic percentage and inflammation, but supplement of curcumin increased the cell viability, reduced pyroptosis and inflammation. Additionally, the expressions of NF-κB and pyroptosis related proteins were notably increased, while Sirtuin 1 (SIRT1) was decreased in both in vivo and in vitro ALI models. The results suggested that curcumin remarkably inhibited the expression of NF-κB and pyroptosis related proteins and increased the expression of SIRT1. However, EX527, a SIRT1 inhibitor, blocked the protective effect of curcumin against ALI. In conclusion, curcumin has protective effect against ALI. It may inhibit inflammatory process by inhibiting the activation of NLRP3 inflammasome-dependent pyroptosis through the up-regulation of SIRT1.

MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3.

INTRODUCTION AND OBJECTIVES: Alcoholic hepatitis (AH) is characterized by high morbidity and mortality. MicroRNA-494-3p is possibly involved in the regulation of cancers, but its role in AH has been rarely studied. MATERIALS AND METHODS: AH mice model and primarily cultured mice hepatic stellate cells (HSCs) model were constructed. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed by ELISA. Expressions of miRNAs, HSC activation-related proteins and fibrosis-related protein were analyzed by qRT-PCR and Western blot. Cell counting kit, colony formation and flow cytometry assays were used to detect cell viability, proliferation and apoptosis, respectively. The relationship between TNF receptor-associated factor 3 (TRAF3) and miR-494-3p was predicted and verified by TargetScan and dual-luciferase assay, respectively. Results of the above experiments were verified by rescue experiments using TRAF3. RESULTS: Liver damage and miRNA expression were observed in AH mice, and AST and ALT levels were increased in serum of AH mice. MiR-494-3p was reduced in AH liver tissues, and it decreased the levels of α-SMA and fibrosis-related proteins. HSCs were isolated, and activating HSCs or upregulating miR-494-3p had a regulatory effect on the levels of miR-494-3p, HSC activation-related proteins and fibrosis-related proteins as well as cell viability, proliferation and apoptosis. In addition, miR-494-3p targeted TRAF3 and inhibited TRAF3 expression, while overexpressed TRAF3 promoted TRAF3 expression and rescued the regulatory effect of miR-494-3p on the levels of related proteins as well as cell viability, proliferation and apoptosis. CONCLUSIONS: This study provided a novel mechanistic comprehension of the anti-fibrotic effect of miR-494-3p.

Risk factors for acute stroke-associated pneumonia and prediction of neutrophil-to-lymphocyte ratios.

OBJECTIVES: This study aimed to analyze the risk factors for stroke-associated pneumonia (SAP) and assess the predictive effect of neutrophil-to-lymphocyte ratio (NLR) on acute SAP. METHODS: The study included acute stroke patients from April 2018 to June 2019. These patients were divided into the SAP and Non-SAP groups. The patients' history of chronic diseases was assessed, including history of hypertension, diabetes, hyperlipidemia, chronic lung disease, and current smoking status. The clinical characteristics of all studied cases were recorded, including the initial stroke type (cerebral infarction or cerebral hemorrhage), National Institute of Health Stroke Scale (NIHSS) score, indwelling nasogastric tubes, stroke-associated pneumonia within 7 days of hospitalization, and length of hospitalization. The study also recorded the laboratory testing data, including fasting blood glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, glycosylated hemoglobin, and high-sensitivity C-reactive protein (hsCRP) as well as white blood cell (WBC), neutrophil, and lymphocyte counts. SPSS 19.0 was used for statistical analysis. RESULTS: A total of 328 eligible acute stroke patients were included. Among all participants, SAP occurred in 64 (19.5%) patients. In the SAP group, the patients were older, the proportion of cerebral hemorrhage was higher, the NIHSS score was higher, and more patients had nasogastric tubes (P < 0.05). Concomitantly, the blood glucose, hsCRP, WBC count, neutrophil count, and NLR of the SAP group were significantly higher than those of the Non-SAP group, whereas the lymphocyte count was significantly lower than that of the Non-SAP group (P < 0.05). Multivariable analysis of Binary Logistic regression revealed that stroke type (cerebral hemorrhage), indwelling gastric tube, and NLR were independent risk factors for SAP. Receiver operating characteristic curve analysis demonstrated that the area under the curve for the NLR's ability to predict SAP was 0.861. The optimal cutoff threshold, sensitivity, and specificity were 3.745, 0.891, and 0.727, respectively. CONCLUSIONS: The risk factors for SAP were multifaceted. Cerebral hemorrhage, indwelling nasogastric tube, and high NLR were independent risk factors. An early NLR had a predictive effect on the occurrence of SAP in patients with acute stroke.

[Effects of dicyandiamide on cadmium accumulation in pakchoi under instant soluble nitrogen fertilizers]. / é€Ÿæ•ˆæ°®è‚¥é æ–½åŒæ°°èƒºå¯¹å‡æŽ§å°ç™½èœé•‰ç§¯ç´¯çš„ä½œç”¨.

We investigated the effects of dicyandiamide (DCD) on the growth and Cd concentrations in pakchoi cultivated under different instant soluble N fertilizers [ammonium sulfate, ammonium sulfate and sodium nitrate (1:1, ammonium/nitrate), and urea] in Cd-contaminated soils. The results showed that the fresh weight of the edible parts of Cd-stressed pakchoi were increased by 583.3%, 41.5%, and 206.8% under ammonium, ammonium/nitrate, and urea treatments in the presence of DCD, respectively compared with control, and the tolerance index and photosynthetic rate significantly increased, whereas no significant changes were observed under nitrate supply. Under all N treatments with DCD, the MDA and H2O2 contents and the superoxide radical production rate in the leaves of pakchoi were decreased, with the highest reduction occurred in ammonium and urea treatments. Cd concentrations in the leaves of pakchoi fertilized with ammonium, ammonium/nitrate, and urea were lowered by 58.3%, 34.0%, and 44.5% and those in the petioles were lowered by 61.8%, 29.4%, and 55.6%, respectively. Cd concentration in the leaves and petioles of pakchoi in the nitrate treatment did not differ significantly from control. These changes could be attributable to the reduction in the acidification of rhizosphere soil in response to the combined application of N fertilizer and DCD. Accordingly, in Cd-contaminated soils with a low buffering capacity, the application of DCD combined with ammonium, ammonium/nitrate, or urea N fertili-zers could alleviate Cd-induced growth stress and inhibit photosynthesis in pakchoi plants and effectively minimize the Cd accumulation.

Macrophage-stimulating activity of European eel (Anguilla anguilla) peptides in RAW264.7 cells mediated via NF-κB and MAPK signaling pathways.

European eel (Anguilla anguilla) is considered to be a vital commercial fish species. In this study, the effect and molecular mechanism of bioactive peptides from European eel on macrophage-stimulating activity in RAW264.7 cells were investigated. Eel peptide (EP) markedly induced NO and iNOS production and promoted TNF-α and IL-6 secretion in a concentration-dependent manner. Moreover, EP dose-dependently activated NF-κB and MAPK signaling pathways in RAW264.7 cells. In addition, EP was purified using a Sephadex A-25 column and a Bio-Gel P-6 column, and the fraction (Fr-1-1) showing the strongest NO-inducing activity was obtained. Then, the molecular weights of the components in Fr-1-1 were analyzed by LC-MS/MS and found to range from 700 to 1900 Da for the majority of components, which suggested that Fr-1-1 mainly consisted of peptides containing 8-20 amino acid residues. Overall, our results indicated that EP from Anguilla anguilla activated macrophages and could be used as a potential nutraceutical or pharmaceutical.

γ-Mangostin Ameliorates Free Fatty Acid-Induced Lipid Accumulation via the SIRT1/LKB1/AMPK Pathway in HepG2 and L02 Cells.

Lipid accumulation is a typical characteristic of nonalcoholic fatty liver disease (NAFLD). The inhibition of lipid accumulation is regarded as a potential treatment for NAFLD. In this study, we investigated the effects of γ-mangostin or α-mangostin on lipid accumulation in a cell model. Analysis of the inhibitory effects of γ-mangostin on lipid accumulation revealed that it downregulated NAFLD-related biochemical parameters and stimulated the SIRT1/LKB1/AMPK pathway. Consequently, it suppressed lipid synthesis and enhanced fatty acid oxidation. Moreover, we demonstrated that the blockage of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C abrogated the promoting effect of AMPK. Similar results were also observed for α-mangostin. The effects of α-mangostin on lipid accumulation were inferior to those of γ-mangostin. The differences in CPT1A activity might be originated from their different chemical structures. Our results suggested that γ-mangostin and α-mangostin can be exploited as potential candidates for NAFLD treatment.

Mental health resources and awareness of anxiety and depressive disorders in general hospitals in China

Abstract Background Mental health disorders are common in China. There is a lack of knowledge and resources of mental health in China. Objectives To assess the levels of psychiatric resources and services in general hospitals in China. Methods Data regarding psychiatric departments, wards and staff were collected from 57 general hospitals in four provinces of China (Hubei, Zhejiang, Heilongjiang and Yunnan) between April 2014 and June 2014. Questionnaires were distributed to 1,200 non-psychiatric clinicians. Results Among the 57 hospitals, 50 provided mental health services, 36 had mental health wards, and seven had neither mental health clinics nor wards. The median number of mental health clinicians was six per hospital. The median number of specialized nurses was 42 per hospital. A total of 1,152 non-psychiatric clinicians with a career duration of 9.4 ± 8.9 years returned completed questionnaires. Only 6.9% reported a good understanding of the manifestation of anxiety and depressive disorders, 4.5% reported a good understanding of the diagnostic criteria, and 3.8% reported a good understanding of the treatment protocols. Discussion There is inadequate awareness of anxiety and depressive disorders among non-psychiatric clinicians in general hospitals in China. This awareness/understanding increased with increasing hospital level.

Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer.

The antipsychotic drug pimozide has been found to exhibit anticancer effects. Previously, it was demonstrated that pimozide inhibits hepatocellular carcinoma (HCC) cell growth, but its pharmacodynamic characteristics remain unclear. The aim of the present study was to investigate the reversibility and mechanism of the ability of pimozide to inhibit cell proliferation in liver cancer. Cell viability was determined by Cell Counting Kit­8 and colony formation assay. The cell cycle distribution was analyzed by flow cytometry with Ki­67 and PI staining. ROS production of HCC cells was detected with DCFH­DA and inhibited with NAC treatment. Western blot assay was performed to detect the expression of related signaling molecules in HCC cells. Our results showed that pimozide promoted G0/G1 phase arrest in HCC cell lines without significant cell death. Its anti­proliferative effects on HCC cells were reversible, consistent with involvement of cell quiescence and reactive oxygen species (ROS) production. Pimozide enhanced inhibition of HCC cell proliferation by sorafenib. In conclusion, elucidation of pimozide's reversible proliferation inhibition in liver cancer and additive activity with a well­established anticancer drug warrants further exploration of the potential of pimozide as an adjuvant anticancer therapy.