Background Chrysotile is widely used in construction and industry. Research has shown that it is associated with lung fibrosis in occupational groups, but the involvement of microRNAs (miRNAs) in chrysotile-induced lung fibrosis has been less well studied, and the specific mechanism is still unclear. Objective Using next-generation sequencing technology to analyze the effects of chrysotile exposure on the miRNAs expression profiles of human lung epithelial cells (BEAS-2B cells), to explore the variations of differentially expressed miRNAs and related signaling pathways, and to identify potential targets and molecular mechanisms of chrysotile-induced lung fibrosis. Methods Chrysotile was analyzed with a laser particle size analyzer and an X-ray diffractometer for particle size and physical phase. BEAS-2B cells were exposed to chrysotile for designed time sessions (12, 24, and 48 h) and doses (0, 50, 100, and 200 μg·mL⁻¹). Cell viability was detected with a cell viability assay kit (CCK8); expression levels of Fibronectin, Collagen-Ⅰ, and α-smooth muscle actin (α-SMA) were detected by Western blot after exposure to 200 μg·mL⁻¹ chrysotile for 24 h. Sample correlation and changes in miRNAs expression profiles between the chrysotile-exposed and the control groups were analyzed by next-generation sequencing technology. The target genes of differentially expressed miRNAs were predicted and subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results The average particle size of the chrysotile dust sample used in this study was 3.58 μm, and the results of X-ray diffraction analysis confirmed the characteristic peaks of chrysotile. Compared with the control group, the chrysotile gradually inhibited the survival rate of BEAS-2B cells with increasing concentration and exposure time (P<0.01). The survival rates of the 50, 100, and 200 μg·mL⁻¹ chrysotile-exposed cells after 12 h exposure were 83.88%±1.86%, 78.07%±3.97%, and 71.95%±2.99%, respectively; the survival rates after 24 h exposure were 77.41%±1.58%, 69.57%±2.23%, and 62.79%±3.65%, respectively; the survival rates after 48 h exposure were 74.31%±4.93%, 65.84%±2.71%, and 52.74%±6.31%, respectively. The Fibronectin, Collagen-Ⅰ, and α-SMA protein expression levels were elevated in the 200 μg·mL⁻¹ chrysotile-exposed BEAS-2B cells (P <0.05). The results of principal component analysis showed that there were differences in the composition of the samples between the chrysotile exposure group and the control group, and a total of 163 differential miRNAs were screened, of which 79 were up-regulated and 84 were down-regulated. The results of GO analysis showed that the differential miRNAs were mainly associated with biological processes such as regulation of transcription by RNA polymerase II, regulation of DNA templated transcription, cellular differentiation, protein phosphorylation, lipid metabolism, and cell cycle, cellular components such as nucleus, cytomembrane, cytoskeleton, mitochondria, and endoplasmic reticulum, as well as molecular functions such as protein binding, metal ion binding, transferase activity, and DNA binding. The results of KEGG analysis revealed that the differential miRNAs were mainly enriched in cancer pathway, phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway, Ras-associated protein 1 (Rap1) pathway, calcium pathway, cyclic guanosine monophosphate/ protein kinase G (cGMP-PKG) pathway, Hippo pathway, cyclic adenosine monophosphate (cAMP) pathway, and Ras pathway. Conclusion Chrysotile exposure could significantly inhibit BEAS-2B cell survival, elevate the expression of lung fibrosis-associated proteins, and induce differential miRNAs expression, affecting biological processes (such as lipid metabolism, protein phosphorylation, and cell cycle) and cell components (such as mitochondria and endoplasmic reticulum), and interfering with PI3K/AKT pathway, Hippo pathway, cAMP pathway, Rap1 pathway, and Ras pathway.

Objective:To construct a transcultural nursing competency framework for master of nursing specialist, providing reference for the cultivation and evaluation of transcultural nursing competency for master of nursing specialist.Methods:From December 2022 to March 2023, based on the cultural awareness, cultural skill, cultural knowledge, cultural encounter and cultural desire (ASKED) model of cultural competency and the group discussion, a preliminary pool of transcultural nursing competency elements for master of nursing specialist was formed using literature analysis, questionnaire survey, and semi-structured interviews. From April to July 2023, purposive sampling was used to select 20 nursing experts from universities and their affiliated hospitals in seven provinces, autonomous regions, and municipalities including Guangdong Province, Guangxi Zhuang Autonomous Region, Beijing City, Zhejiang Province, Hebei Province, Hunan Province, and Shaanxi Province as consultant experts. The transcultural nursing competency framework for master of nursing specialist was established using the Delphi method.Results:A total of 17 experts completed two rounds of consultation. The positive coefficients of the two rounds of expert consultation were 85.00% (17/20) and 100.00% (17/17), respectively. The authority coefficients of the two rounds of consultant experts were 0.826 and 0.878, respectively. The Kendall harmony coefficients for the first and second level elements in the second round of expert consultation were 0.302 ( P<0.01) and 0.304 ( P<0.01). After two rounds of expert consultations, a transcultural nursing competency framework for master of nursing specialist was established, which included five first-level elements of cultural awareness, cultural attitude, cultural knowledge, cultural skills, and cultural interaction, as well as 21 second-level elements. Conclusions:The transcultural nursing competency framework for master of nursing specialist is scientific and reliable, which can provide reference for formulating transcultural nursing competency standards for master of nursing specialist and lay a foundation for improving their cross-cultural nursing competency.

Background Alcohol dependence and related health problems have attracted greater than ever attention in recent years.Alcohol dependence not only affected personal behavior control ability,but also brought adverse effect to families and society.Objective To analyze the relationship between cognitive function and personality traits among male alcohol-dependent patients with aggressive behavior,in order to provide references for improving the cognitive function of male alcohol-dependent patients with aggressive behavior.Methods Male patients with alcohol dependence attending Hunan Brain Hospital from March 2020 to March 2022 and fulfilling the International Classification of Diseases,tenth edition(ICD-10)diagnostic criteria were enrolled.According to the score of Modified Overt Aggression Scale(MOAS),participants were classified into aggressive behavior group and non-aggressive behavior group at 1∶1 ratio,each with 80 cases.The enrolled subjects were then evaluated using Revised Eysenck Personality Questionnaire Short Scale for Chinese(EPQ-RSC)and Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).Pearson correlation analysis was utilized to examine the correlation between EPQ-RSC and RBANS scores among alcohol-dependent patients with aggressive behavior.Results Scores on each subscale in RBANS were all lower in aggressive behavior group than those in non-aggressive behavior group(t=2.176,2.580,2.076,2.308,2.193,P<0.05),and scores on each dimension in EPQ-RSC in aggressive behavior group were higher than those in non-aggressive behavior group(t=4.497,5.242,6.459,P<0.01).Pearson correlation analysis denoted that the scores of introversion/extroversion,neuroticism and psychoticism in EPQ-RSC were positively correlated with the scores of immediate memory,visuospatial/constructional ability,language,attention and delayed memory in RBANS among alcohol-dependent patients with aggressive behavior(r=0.294～0.482,0.362～0.511,0.265～0.475,P<0.05).Conclusion The cognitive function may have a certain correlation with personality traits in alcohol-dependent patients with aggressive behavior.

Objectives:Aimed to establish a rapid, high-throughput, automated method for determining the creatine kinase (CK-MM) isoform levels.Methods:Magnetic beads labeled with anti-CK-MM antibodies were combined with alkaline phosphatase-based chemiluminescence detection. Clinical and diagnostic performance validation of the assay was determined by analysis of 998 and 75 dried blood spot samples from healthy newborns and Duchenne muscular dystrophy (DMD) patients, respectively, and the CK activity was also determined. The blank and detection limits, cross-reactivity, recovery rate of the method, intra-and inter-assay coefficient, and the hook effect were evaluated.Results:Blank and detection limits were 17.4 and 39.3 ng/ml, respectively. Cross-reactivity toward CK-MB and CK-BB isoforms was 0.2% and 0.02%, respectively. Intra-and inter-assay coefficients of variation were<1%. Mean recovery was 100.32%, with no hook effect in CK-MM levels<50 000 ng/ml. Overall, the mean CK-MM concentrations in newborns and DMD patients were (27.05±0.97) and (3 720±300.5) ng/ml, respectively. A significant positive correlation between the dried blood spot detected CK-MM levels and total CK enzyme activity, evaluated in corresponding serum samples from the 75 DMD patients, was observed ( r=0.91, P<0.001), ?which is in good agreement with the clinical. Conclusions:An assay for rapid quantitative determination of CK-MM that meets clinical newborn screening requirements was established. It had a good value for application.

Objective:To analyze the influencing factors and improvement paths of the cultivation of full-time doctoral scientific and technological innovation ability in large public hospitals, and propose countermeasures and suggestions.Methods:This studyed conducted a survey and analysis of 122 doctors from Linyi People′s Hospital in Shandong Province, and completed a current situation study based on the analysis results.Results:There was no significant difference between the two groups in gender, age, degree type, professional category, discipline level, Graduate School type, job type and other indicators. There were significant differences between the two groups in scientific research topic selection ability score, project design ability score, data analysis ability score, data interpretation ability score, project approval in recent 5 years, project level, number of SCI journal papers published in recent 5 years, cumulative impact factors of SCI journal papers, and annual number of academic activities ( P<0.05). Conclusions:The hospital can improve the scientific and technological innovation ability of full-time doctors by setting up a special cultivation plan, establishing an interdisciplinary team, optimizing scientific research management services, improving the evaluation and assessment system, and improving welfare protection.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

ObjectiveTo investigate the impact of posture and sports experience on distance perception in Paralympic athletes with lower limbs disabilities. MethodsFrom May to August, 2019, athletes were selected from the wheelchair racing team (n = 19) and the wheelchair fencing team (n = 16) in Shanghai, China. The athletes were tested the relative distance perception and absolute distance perception using the successive equal-appearing distance and blind walking tasks. ResultsThe interaction effects between sport and posture (F = 4.118, P < 0.05), sports events and distance judgment (F = 8.913, P < 0.01), and posture and distance judgment (F = 11.894, P < 0.01) were significant; while the main effects of sport (F = 7.467, P < 0.01) and posture (F = 11.918, P < 0.01) were significant; the relative distance judgment accuracy was better in the athletes of wheelchair fencing than in those of wheelchair racing, and in standing posture than those in sitting posture. ConclusionThe relative distance judgment accuracy is better for the Paralympic athletes standing and playing wheelchair fencers. There was no significant difference in the accuracy of absolute distance judgment between the different postures and the different sports.

Liver transplantation is a vital treatment for end-stage liver disease. However, the shortage of donor livers has limited the development of liver transplantation. How to expand the source of donor livers has become a challenge in the academic community. In recent years, the proportion of donors with non-alcoholic fatty liver disease (NAFLD) has been increased. Rational use of steatotic donor livers is a feasible approach to expand the donor pool. Cold ischemia injury during donor liver preservation before liver transplantation increases the risk of postoperative organ dysfunction. Therefore, it is of significance to unravel the mechanism and intervention measures of cold ischemia injury of steatotic donor livers. Cold ischemia injury of steatotic donor livers is characterized as the damage of mitochondria, lysosomes and endoplasmic reticulum at the organelle level, and up-regulated expression of adenosine monphosphate activated protein kinase (AMPK), aldehyde dehydrogenase 2 (ALDH2) and heme oxygenase (HO)-1 at the protein level. In this article, the research progresses on cold ischemia injury of steatotic donor livers and relevant intervention measures were reviewed.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.